Publications by authors named "Asle Aarsland"

31 Publications

Clearance of Indocyanine Green in Severe Pediatric Burns.

J Trauma Acute Care Surg 2019 05;86(5):817-822

From the Department of Surgery (E.C.D., D.N.H., A.A., E.B.), University of Texas Medical Branch, Galveston, Texas; Metabolism Unit (E.C.D., D.N.H., R.P.M., E.B.), Shriners Hospitals for Children, Galveston, Texas; Department of Surgery (A.A.), University of Texas Medical Branch, Galveston, Texas; Haukeland University Hospital, Bergen, Norway; Department of Pediatrics (E.C.D., M.A.C., E.B.), University of Arkansas for Medical Sciences, Little Rock, Arkansas; Arkansas Children's Nutrition Center (E.C.D., M.A.C., E.B.), Little Rock, Arkansas; and Arkansas Children's Research Institute (E.C.D., M.A.C., E.B.), Little Rock, Arkansas.

Background: Clearance of indocyanine green dye (ICGc) reflects sinusoidal perfusion and hepatocyte cell membrane function. Thus, ICGc is a reflection of the functional reserve of intact hepatocytes. The purpose of this study was to identify predictors of ICGc in severely burned children during the acute hospitalization and at the time of discharge from the intensive care unit (ICU). A secondary aim was to determine the relationship between liver size and patient ICGc.

Methods: Twenty-six children (0.8-17 years old) with 35% or greater total body surface area burned (%TBSA-B) were included. Assessment of ICGc (in milliliters per minute per meter squared) was done during the acute hospitalization (median: 6 days after admission, median: 14 days postburn) and at the time of discharge from the ICU (median: 19 days after admission, median: 27 days postburn). Age, TBSA-B, % third-degree burns, inhalation injury, preexisting chronic malnutrition, hematocrit, liver dysfunction, and time from burn injury were incorporated in multiple linear regressions as predictive variables of ICGc. Only variables with p < 0.05 were retained in the final models.

Results: Time from injury and age were the strongest predictors of ICGc during the acute admission but not at the time of discharge from the ICU. Time from injury was negatively associated with ICGc, whereas age was positively associated. At the time of discharge from the ICU, ICGc was increased in proportion to the %TBSA-B, whereas inhalation injury and preexisting chronic malnutrition were associated with lower ICGc. There was no correlation between change-to-predicted liver length and ICGc.

Conclusions: The intrinsic ability of the liver to extract ICG from plasma was lower in younger burned patients during the acute admission and in those with preexisting chronic malnutrition and inhalation injury at the time of discharge from the ICU.

Level Of Evidence: Prognostic/Epidemiologic, level III.
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http://dx.doi.org/10.1097/TA.0000000000002180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6476649PMC
May 2019

Long-term oxandrolone treatment increases muscle protein net deposition via improving amino acid utilization in pediatric patients 6 months after burn injury.

Surgery 2011 May 18;149(5):645-53. Epub 2011 Feb 18.

Department of Surgery, University of Texas Medical Branch, Galveston, TX 77555-1220, USA.

Background: We recently showed that mechanisms of protein turnover in skeletal muscle are unresponsive to amino acid (AA) infusion in severely burned pediatric patients at 6 months postinjury. In the current study, we evaluated whether oxandrolone treatment affects mechanisms of protein turnover in skeletal muscle and whole-body protein breakdown in pediatric burn patients 6 months postinjury.

Methods: At the time of admission, patients were randomized to control or oxandrolone treatments. The treatment regimens were continued until 6 months postinjury, at which time patients (n = 26) underwent study with a stable isotope tracer infusion to measure muscle and whole-body protein turnover.

Results: Protein kinetics in leg muscle were expressed in nmol/min per 100 mL leg volume (mean ± SE). During AA infusion, rates of protein synthesis in leg muscle were increased (P < .05) in both groups (basal vs AA: control, 51 ± 8 vs 86 ± 21; oxandrolone, 56 ± 7 vs 96 ± 12). In the control group, there was also a simultaneous increase in breakdown (basal vs AA: 65 ± 10 vs 89 ± 25), which resulted in no change in the net balance of leg muscle protein (basal vs AA: -15 ± 4 vs -2 ± 10). In the oxandrolone group, protein breakdown did not change (basal vs AA: 80 ± 12 vs 77 ± 9), leading to increased net balance (basal vs AA: -24 ± 7 vs 19 ± 7; P < .05). Protein breakdown at the whole-body level was not different between the groups.

Conclusion: Long-term oxandrolone treatment increased net deposition of leg muscle protein during AA infusion by attenuating protein breakdown, but did not affect whole-body protein breakdown.
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http://dx.doi.org/10.1016/j.surg.2010.12.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3079061PMC
May 2011

Intensive insulin treatment increases donor site wound protein synthesis in burn patients.

Surgery 2011 Apr 14;149(4):512-8. Epub 2011 Jan 14.

Metabolism Unit, Shriners Hospital for Children, Galveston, TX 77550-1220, USA.

Background: In the treatment of burns, patients' own skin is the preferred material to cover burn wounds, resulting in the need to create a donor site wound. Enhancement of healing of the donor site wound would be beneficial in burn patients. Insulin, an anabolic agent, is used routinely to treat hyperglycemia after injury. We investigated whether intensive insulin treatment increases fractional synthesis rate (FSR) of the donor site wound protein and decreases the length of hospitalization normalized for total body surface area burned (LOS/TBSA).

Methods: FSR of the donor site wound protein was measured in pediatric patients randomized to control (n = 13) and insulin (n = 10) treatments. Depending on the postoperative day when the tracer study was done, studies were divided into "early" (days < 5) and "late" (days ≥ 5) periods.

Results: FSR of the donor site wound protein was greater in the insulin group at the "early" period of wound healing (control vs insulin, 8.2 ± 3.8 vs 13.1 ± 6.9% per day; P < .05); but not at the "late" (control vs insulin, 19.7 ± 4.6 vs 16.6 ± 4.0% per day; P > .05). Despite these differences, LOS/TBSA was not decreased in the insulin group. Correlation analyses demonstrated that, independent of the treatment regimen, FSR positively correlated (P < .05) with time after creation of the donor site and negatively correlated (P < .05) with LOS/TBSA.

Conclusion: Insulin treatment increased FSR of the donor site wound protein in the early period of wound healing; FSR correlated with LOS/TBSA independent of the treatment regimen.
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http://dx.doi.org/10.1016/j.surg.2010.10.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3775333PMC
April 2011

Donor site wound protein synthesis correlates with length of acute hospitalization in severely burned children.

Wound Repair Regen 2010 May-Jun;18(3):277-83. Epub 2010 Apr 14.

Department of Surgery, University of Texas Medical Branch, Galveston, TX 77550-1220, USA.

Autografting of burn wounds results in generation of donor site wounds. Here we measured donor site wound protein fractional synthesis rate (FSR) in a burn pediatric population and showed that FSR increases over time postsurgery and correlates with the length of hospital stay (LOS) normalized for total body surface area (TBSA) burn size. 3.9 +/- 1.1 days after the grafting surgery patients participated in a metabolic study consisting of continuous infusion of l-[ring-(2)H(5)]-phenylalanine and donor site wound punch biopsies. Donor site wound protein FSR was 10.4 +/- 7.5%/day. Wound FSR demonstrated linear correlation with the time postsurgery (p<0.05). Multiple regression analysis showed that LOS/TBSA correlated with donor site wound protein FSR and time postsurgery (p<0.001) and the following equation describes the relationship: estimated LOS/TBSA=(FSR-12.95-1.414 x postsurgery day)/(-17.8). This equation predicted that FSR corrected for the postsurgery day when the metabolic study was conducted accounted for 67% of the variability (r(2)=0.673) in the LOS/TBSA. Donor site wound protein FSR correlated to LOS/TBSA of burn patients admitted to the intensive care unit. Measurement of protein deposition in regenerating donor site wound using stable isotope technique provides a quantitative measure of wound healing.
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http://dx.doi.org/10.1111/j.1524-475X.2010.00584.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3905463PMC
October 2010

Twenty-eight-day bed rest with hypercortisolemia induces peripheral insulin resistance and increases intramuscular triglycerides.

Metabolism 2010 May 17;59(5):703-10. Epub 2009 Nov 17.

Metabolism Unit, Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston TX 77550, USA.

Spaceflight represents a unique physiologic challenge to humans, altering hormonal profiles and tissue insulin sensitivity. Among these hormonal alterations, hypercortisolemia and insulin insensitivity are thought to negatively affect muscle mass and function with spaceflight. As insulin sensitivity influences the accumulation of muscle triglycerides, we examined this relationship during hypercortisolemia and inactivity. Six young healthy volunteers were confined to bed rest for 28 days. To mimic the stress response observed during spaceflight, hypercortisolemia (20-24 mg/dL) was induced and maintained by oral ingestion of hydrocortisone. On days 1 and 28 of bed rest, insulin sensitivity across the leg was assessed with a local (femoral arterial insulin infusion) 2-stage hyperinsulinemic-euglycemic clamp (stage 1, 35 microU/min per milliliter of leg; stage 2, 70 microU/min per milliliter of leg). Intramuscular lipid was measured with magnetic resonance spectroscopy. After bed rest, there was a decrease in insulin sensitivity, as assessed by glucose uptake during hyperinsulinemia (from 9.1 +/- 1.3 [mean +/- SEM] to 5.2 +/- 0.7 mg/kg of leg per minute [P = .015]). Intramuscular triglyceride increased from 0.077 +/- 0.011 to 0.136 +/- 0.018 (signal area of fat/signal area of standard, P = .009). Intramuscular lipid content correlated with the glucose uptake at day 28 (R = -0.85, P = .035). These data demonstrate that muscular inactivity and hypercortisolemia are associated with an increase in intramuscular triglyceride and skeletal muscle insulin resistance in previously healthy subjects.
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http://dx.doi.org/10.1016/j.metabol.2009.09.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2856785PMC
May 2010

Intranasal dexmedetomidine premedication is comparable with midazolam in burn children undergoing reconstructive surgery.

J Burn Care Res 2009 Jul-Aug;30(4):599-605

Department of Anesthesia, Shriners Hospital for Children, and Department of Anesthesiology, University of Texas Medical Branch-Galveston, Galveston, Texas 77550, USA.

Preoperative anxiety and emergence delirium in children continue to be common even with midazolam premedication. Midazolam is unpleasant tasting even with a flavored vehicle and as a result, patient acceptance is sometimes poor. As an alternative, we evaluated dexmedetomidine administered intranasally. Dexmedetomidine an alpha-2 adrenergic agonist is tasteless, odorless, and painless when administered by this route. Alpha-2 adrenergic agonists produce sedation, facilitate parental separation, and improve conditions for induction of general anesthesia, while preserving airway reflexes. Institutional review board approval was obtained to study 100 pediatric patients randomized to intranasal dexmedetomidine (2 microg/kg) or oral midazolam (0.5 mg/kg) administered 30 to 45 minutes before the surgery. Subjects received general anesthesia with oxygen, nitrous oxide, isoflurane, and analgesics (0.05-0.1 mg/kg morphine or 0.1 mg/kg methadone). Nurses and anesthetists were blinded to the drug administered and evaluated patients for preoperative sedation, conditions for induction of general anesthesia, emergence from anesthesia, and postoperative pain. Responses of 100 patients (50 dexmedetomidine and 50 midazolam) were analyzed. Dexmedetomidine (P=.003) was more effective than midazolam at inducing sleep preoperatively. Dexmedetomidine and midazolam were comparable for conditions at induction (P>0.05), emergence from anesthesia (P>0.05), or postoperative pain (P>0.05). Both drugs were equieffective in these regards. In pediatric patients, dexmedetomidine 2 microg/kg administered intranasally and midazolam 0.5 mg/kg administered orally produced similar conditions during induction and emergence of anesthesia. Intranasal administration of dexmedetomidine is more effective at inducing sleep and in some circumstances offers a useful alternative to oral midazolam in children.
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http://dx.doi.org/10.1097/BCR.0b013e3181abff90DOI Listing
August 2009

Muscle protein synthesis and balance responsiveness to essential amino acids ingestion in the presence of elevated plasma free fatty acid concentrations.

J Clin Endocrinol Metab 2009 Aug 19;94(8):2984-90. Epub 2009 May 19.

Center for Metabolic Biology, Arizona State University, Tempe, AZ 85287-3704, USA.

Context: Elevated plasma free fatty acid (FFA) concentrations are observed under various clinical circumstances and are associated with impaired glucose disposal in skeletal muscle.

Objective: The aim of the study was to determine the effects of elevated plasma FFA concentrations on the response of protein synthesis and balance in muscle after essential amino acids (EAAs) ingestion.

Design: Leg protein kinetics were determined in young healthy individuals before and after the ingestion of EAAs at 10 h after the initiation of either lipid (Liposyn/heparin+EAA) or saline (saline+EAA) infusions.

Results: Plasma insulin responses where higher (P <0.05) in the Liposyn/heparin+EAA group than the saline+EAA group both before (14 +/- 4 vs. 6 +/- 1 microIU . ml(-1)) and after (1038 +/- 257 vs. 280 +/- 87 microIU . ml(-1) . 210 min(-1)) the EAA ingestion. After the EAA ingestion, the rates of both leg phenylalanine disappearance (Rd; nmol . min(-1) . kg lean leg mass(-1)) and muscle proteins fractional synthesis (FSR; % . h(-1)) increased (P <0.05) in both the Liposyn/heparin+EAA and saline+EAA groups, but these changes were not different between the two groups (Rd, 102 +/- 32 vs. 118 +/- 34; FSR, 0.014 +/- 0.005 vs. 0.018 +/- 0.007; P > 0.05). Although the leg phenylalanine rate of appearance (Ra; nmol . min(-1) . kg lean leg mass(-1)) was lower (381 +/- 47 vs. 518 +/- 40) and the balance was greater (-109 +/- 20 vs. -172 +/- 17) in the Liposyn/heparin+EAA group compared to the saline+EAA group before the EAA ingestion (P <0.05), the changes in both of these parameters were not different between groups after the EAA ingestion (P > 0.05).

Conclusions: Elevated plasma FFA concentrations do not interfere with the response of muscle protein synthesis and balance to a bolus ingestion of EAAs.
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http://dx.doi.org/10.1210/jc.2008-2686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2730875PMC
August 2009

Acute propranolol infusion stimulates protein synthesis in rabbit skin wound.

Surgery 2009 May 21;145(5):558-67. Epub 2009 Mar 21.

Shriners Hospital for Children, Galveston, TX, USA.

Background: Propranolol administration has been demonstrated to improve cardiac work, decrease energy expenditure, and attenuate lipolysis in burned patients; however, its effect on wound healing has not been reported.

Methods: In rabbits, a partial-thickness skin donor site wound was created on the back, and catheters were placed in the carotid artery and jugular vein. A nasogastric feeding tube was placed for enteral feeding. On day 5 after injury, stable isotope tracers were infused to determine protein and DNA kinetics in the wound. Propranolol hydrochloride was injected in 1 group during the tracer infusion to decrease heart rate, and the other group without propranolol injection served as a control.

Results: The propranolol infusion decreased heart rate by 21%. The protein fractional synthetic rate in the wound was greater in the propranolol group (8.6 +/- 0.9 vs 6.1 +/- 0.5%/day, P < .05). Wound protein fractional breakdown rates were not significantly different. The rate of protein deposition (synthesis - breakdown) was increased in the propranolol group (5.0 +/- 1.2 vs 2.8 +/- 0.7%/day, P = .07). Wound DNA fractional synthetic rates were comparable. The protein fractional synthetic rate was correlated with percent decrease in heart rate, but expression of the beta-adrenergic receptors and downstream signaling cascades in local wounds were not affected after propranolol treatment.

Conclusion: Propranolol infusion increased wound protein synthetic rate and tended to increase wound protein deposition rate, which might be beneficial to wound healing. These changes might reflect a systemic response to the beta-adrenergic blockade.
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http://dx.doi.org/10.1016/j.surg.2009.01.006DOI Listing
May 2009

Stimulation of muscle anabolism by resistance exercise and ingestion of leucine plus protein.

Appl Physiol Nutr Metab 2009 Apr;34(2):151-61

Metabolism Unit, Shriners Hospitals for Children, University of Texas Medical Branch, Galveston, TX 77555, USA.

Leucine is known to stimulate muscle protein synthesis and anabolism. However, evidence for the efficacy of additional leucine to enhance the response of muscle anabolism to resistance exercise and protein ingestion is unclear. Thus, we investigated the response of net muscle protein balance to ingestion of additional leucine with protein in association with resistance exercise. Two groups of untrained subjects performed an intense bout of leg resistance exercise following ingestion of 1 of 2 drinks: flavored water (PL); or 16.6 g of whey protein + 3.4 g of leucine (W+L). Arteriovenous amino acid balance across the leg was measured to assess the anabolic response of muscle in each group. Arterial amino acid concentrations increased in response to ingestion of W+L. Amino acid concentrations peaked between 60 and 120 min after ingestion, and then declined to baseline values. Valine concentration decreased to levels significantly lower than baseline. Net balance of leucine, threonine, and phenylalanine did not change following PL ingestion, but increased and remained elevated above baseline for 90-120 min following W+L ingestion. Leucine (138 +/- 37 and -23 +/- 23 mg), phenylalanine (58 +/- 28 and -38 +/- 14 mg), and threonine (138 +/- 37 and -23 +/- 23 mg) uptake was greater for W+L than for PL over the 5.5 h following drink ingestion. Our results indicate that the whey protein plus leucine in healthy young volunteers results in an anabolic response in muscle that is not greater than the previously reported response to whey protein alone.
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http://dx.doi.org/10.1139/H09-006DOI Listing
April 2009

Arteriovenous differences in plasma dilution and the distribution kinetics of lactated ringer's solution.

Anesth Analg 2009 Jan;108(1):128-33

Clinical Research Center, Södertalje Hospital, Södertalje, Sweden.

Background: Conventional concept suggests that infused crystalloid fluid is first distributed in the plasma volume and then, since the capillary permeability for fluid is very high, almost instantly equilibrates with the extracellular fluid space. We challenge whether this view is consistent with findings based on volume kinetic analysis.

Methods: Fifteen volunteers received an IV infusion of 15 mL/kg of lactated Ringer's solution during 10 min. Simultaneous arterial and venous blood hemoglobin (Hgb) samples were obtained and Hgb concentrations measured. The arteriovenous (AV) difference in Hgb dilution in the forearm was determined and a volume kinetic model was fitted to the series of Hgb concentrations in arterial and venous blood.

Results: The AV difference in plasma dilution was only positive during the infusion and for 2.5 min thereafter, which represents the period of net flow of fluid from plasma to tissue. Kinetic analysis showed that volume expansion of the peripheral fluid space began to decrease 14 min (arterial blood) and 20 min (venous blood) after the infusion ended. Distribution of lactated Ringer's solution apparently occurs much faster in the forearm than in the body as a whole. Therefore, the AV difference in the arm does not accurately reflect the distribution of Ringer's solutions or whole-body changes in plasma volume.

Conclusions: The relatively slow whole-body distribution of lactated Ringer's solution, which boosts the plasma volume expansion during and for up to 30 min after an infusion, is probably governed by a joint effect of capillary permeability and differences in tissue perfusion between body regions.
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http://dx.doi.org/10.1213/ane.0b013e31818c95e1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4406226PMC
January 2009

Whey protein ingestion in elderly persons results in greater muscle protein accrual than ingestion of its constituent essential amino acid content.

Nutr Res 2008 Oct;28(10):651-8

Center for Metabolic Biology, Arizona State University, PO Box 873704, Tempe, AZ 85287-3704, USA.

It is recognized that both whey protein (WY) and essential amino acids (EAA) are stimuli for muscle protein anabolism. The aim of the present study was to determine if the effects of WY ingestion on muscle protein accrual in elderly persons are due solely to its constituent EAA content. Fifteen elderly persons were randomly assigned to ingest a bolus of either 15 g of WY, 6.72 g of EAA, or 7.57 g of nonessential amino acids (NEAA). We used the leg arteriovenous model to measure the leg phenylalanine balance, which is an index of muscle protein accrual. Phenylalanine balance (nmol x min(-1) kg lean leg mass(-1)) during the 3.5 hours after the bolus ingestion improved in the WY (-216 +/- 14 vs -105 +/- 19; P < .05) but not in the EAA (-203 +/- 21 vs -172 +/- 38; P > .05) or NEAA groups (-203 +/- 19 vs -204 +/- 21; P > .05). The insulin response (uIU x mL(-1) 210 min(-1)) during the same period was lower in both the NEAA (48 +/- 40) and EAA (213 +/- 127) when compared to the WY (1073 +/- 229; P < .05). In conclusion, WY ingestion improves skeletal muscle protein accrual through mechanisms that are beyond those attributed to its EAA content. This finding may have practical implications for the formulation of nutritional supplements to enhance muscle anabolism in older individuals.
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http://dx.doi.org/10.1016/j.nutres.2008.06.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2612691PMC
October 2008

Human mitochondrial oxidative capacity is acutely impaired after burn trauma.

Am J Surg 2008 Aug;196(2):234-9

Department of Preventive Medicine and Community Health, The University of Texas Medical Branch, Galveston, TX, USA.

Background: Mitochondrial proteins and genes are damaged after burn injury in animals and are assessed in human burn patients in this study.

Methods: The rates of maximal muscle mitochondrial oxidative capacity (adenosine triphosphate production) and uncoupled oxidation (heat production) for both palmitate and pyruvate were measured in muscle biopsies from 40 children sustaining burns on more than 40% of their body surface area and from 13 healthy children controls.

Results: Maximal mitochondrial oxidation of pyruvate and palmitate were reduced in burn patients compared with controls (4.0 +/- .2:1.9 +/- .1 micromol O2/citrate synthase activity/mg protein/min pyruvate; control:burn; P < .001 and 3.0 +/- .1: .9 +/- .03 micromol O2/citrate synthase activity/mg protein/min palmityl CoA; control:burn; P = .003). Uncoupled oxidation was the same between groups.

Conclusions: The maximal coupled mitochondrial oxidative capacity is severely impaired after burn injury, although there are no alterations in the rate of uncoupled oxidative capacity. It may be that the ratio of these indicates that a larger portion of energy production in trauma patients is wasted through uncoupling, rather than used for healing.
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http://dx.doi.org/10.1016/j.amjsurg.2007.09.048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3480314PMC
August 2008

Insulin sensitivity is related to fat oxidation and protein kinase C activity in children with acute burn injury.

J Burn Care Res 2008 Jul-Aug;29(4):585-94

Department of Preventive Medicine and Community Health, The University of Texas Medical Branch, Galveston, Texas, USA.

Impaired fatty acid oxidation occurs with type 2 diabetes and is associated with accumulations of intracellular lipids, which may increase diacylglycerol (DAG), stimulate protein kinase C activity, and inactivate insulin signaling. Glucose and fat metabolism are altered in burn patients, but have never been related to intracellular lipids or insulin signaling. Thirty children sustaining >40% total body surface area burns were studied acutely with glucose and palmitate tracer infusions and a hyper-insulinemic euglycemic clamp. Muscle triglyceride, DAG, fatty acyl CoA, and insulin signaling were measured. Liver and muscle triglyceride levels were measured with magnetic resonance spectroscopy. Muscle samples from healthy children were controls for DAG concentrations. Insulin sensitivity was reduced and correlated with whole body palmitate beta-oxidation (P = .004). Muscle insulin signaling was not stimulated by hyper-insulinemia. Tissue triglyceride concentrations and activated protein kinase C-beta were elevated, whereas the concentration of DAG was similar to the controls. Free fatty acid profiles of muscle triglyceride did not match DAG. Insulin resistance following burn injury is accompanied by decreased insulin signaling and increased protein kinase C-beta activation. The best metabolic predictor of insulin resistance in burned patients was palmitate oxidation.
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http://dx.doi.org/10.1097/BCR.0b013e31817db88fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3905468PMC
November 2008

Lipid metabolism in diet-induced obese rabbits is similar to that of obese humans.

J Nutr 2008 Mar;138(3):515-8

Metabolism Unit, Shriners Hospital for Children, Galveston, TX 77550, USA.

Whereas diet-induced obese rabbits have been used to study various aspects of obesity, alterations of lipid metabolism in this model have not been clarified. This study aimed to compare plasma nonesterified fatty acid (NEFA) and triglyceride (TG) kinetics in obese and lean rabbits by means of U-(13)C16-palmitate infusion. Young female rabbits consumed either a high-fat diet (49% energy from fat) ad libitum to develop obesity (n = 6) or a normal diet (7.9% energy from fat) as lean control (n = 5). After 10 wk of feeding, the body weight of obese rabbits (5.33 +/- 0.05 kg) was greater (P < 0.001) than that of lean rabbits (3.89 +/- 0.07 kg). The obese rabbits had higher concentrations of plasma NEFA and TG and a greater rate of fatty acid (FA) turnover. Whereas the fractional secretion rates of hepatic TG did not differ, 100% of hepatic secretory TG was synthesized from plasma NEFA in the lean rabbits compared to 59% in the obese rabbits (P < 0.001). In the lean rabbits, hepatic lipase-mediated hydrolysis of lipoprotein TG did not contribute to the FA pool for synthesis of secretory TG, consistent with the naturally occurring deficit in hepatic lipase in this species. We conclude that lipid metabolism in diet-induced obese rabbits is similar to that in obese humans. The deficiency in hepatic lipase in rabbits simplifies the quantitation of hepatic lipid kinetics.
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http://dx.doi.org/10.1093/jn/138.3.515DOI Listing
March 2008

Plasma triglycerides are not related to tissue lipids and insulin sensitivity in elderly following PPAR-alpha agonist treatment.

Mech Ageing Dev 2007 Oct 15;128(10):558-65. Epub 2007 Aug 15.

Department of Preventive Medicine and Community Health, The University of Texas Medical Branch, Galveston, TX 77555, United States.

Increases in plasma lipids, tissue triglycerides and decreases in mitochondrial function have been linked to insulin resistance and aging. In animals, peroxisome proliferator-activated receptor-alpha (PPAR-alpha) agonists decrease plasma lipids, intramyocellular fat (IMCL) and liver fat (LFAT) and improve mitochondrial beta-oxidative function and insulin sensitivity, but the effects in elderly were not known. Insulin sensitivity was assessed with a 2-h oral glucose tolerance test, magnetic resonance spectroscopy was used to asses IMCL, LFAT and plasma lipids were measured before and after 6, 11 and 61 days of PPAR-alpha agonist (fenofibrate) administration in 19 elderly (age 70+/-1 years) volunteers. Volunteers were stratified into healthy (N=7) and insulin resistant (N=12) groups. The baseline insulin sensitivity index (8.1+/-1.2 vs. 3.8+/-0.5, healthy vs. insulin resistant; P<0.001) was significantly higher in the healthy group. Fenofibrate treatment induced significant reductions in plasma triglycerides (P<0.001) and total cholesterol (P<0.001) in both groups. Nonetheless, neither fasted free fatty acids, glucose, insulin, nor insulin sensitivity improved in either group (day 1 vs. day 61, 8.1+/-1.2 vs. 8.1+/-0.9, healthy; and 3.8+/-0.5 vs. 4.2+/-0.05, insulin resistant). Furthermore, there was no change in IMCL or LFAT. These results indicate that whereas fenofibrate significantly lowers plasma lipids it neither affects insulin sensitivity nor intracellular lipids in elderly.
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http://dx.doi.org/10.1016/j.mad.2007.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3503242PMC
October 2007

Role of fat metabolism in burn trauma-induced skeletal muscle insulin resistance.

Crit Care Med 2007 Sep;35(9 Suppl):S476-83

University of Arkansas Medical Sciences, Donald W. Reynolds Center on Aging, Nutrition, Metabolism and Exercise Lab, Little Rock, AR, USA.

Objective: Review current evidence on the role of fat in post-trauma insulin resistance, in reference to new studies with peroxisome proliferating activating receptor-alpha agonists.

Design: Review.

Setting: University laboratory.

Patients: Thirty pediatric burn trauma patients.

Interventions: Fourteen days of peroxisome proliferating activating receptor-alpha agonist immediately following burn trauma.

Measurements And Main Results: We measured glucose metabolism and fat metabolism via tracer methodology and intracellular measurements. Insulin-stimulated glucose uptake is impaired following burn trauma, as is intracellular insulin signaling, palmitate oxidation, and mitochondrial oxidative capacity. Furthermore, levels of intracellular lipids are increased. Two weeks of peroxisome proliferating activating receptor-alpha treatment significantly reverses these pathologic changes incurred from burn injury.

Conclusions: Severe burn injury seriously affects multiple aspects of glucose and fat metabolism within the muscle, which can adversely affect clinical outcomes. Treatment with a peroxisome proliferating activating receptor-alpha drug may be a potential new therapeutic option.
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http://dx.doi.org/10.1097/01.CCM.0000278066.05354.53DOI Listing
September 2007

PPAR-alpha agonism improves whole body and muscle mitochondrial fat oxidation, but does not alter intracellular fat concentrations in burn trauma children in a randomized controlled trial.

Nutr Metab (Lond) 2007 Apr 23;4. Epub 2007 Apr 23.

Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston, USA.

Background: Insulin resistance is often associated with increased levels of intracellular triglycerides, diacylglycerol and decreased fat beta-oxidation. It was unknown if this relationship was present in patients with acute insulin resistance induced by trauma.

Methods: A double blind placebo controlled trial was conducted in 18 children with severe burn injury. Metabolic studies to assess whole body palmitate oxidation and insulin sensitivity, muscle biopsies for mitochondrial palmitate oxidation, diacylglycerol, fatty acyl Co-A and fatty acyl carnitine concentrations, and magnetic resonance spectroscopy for muscle and liver triglycerides were compared before and after two weeks of placebo or PPAR-alpha agonist treatment.

Results: Insulin sensitivity and basal whole body palmitate oxidation as measured with an isotope tracer increased significantly (P = 0.003 and P = 0.004, respectively) after PPAR-alpha agonist treatment compared to placebo. Mitochondrial palmitate oxidation rates in muscle samples increased significantly after PPAR-alpha treatment (P = 0.002). However, the concentrations of muscle triglyceride, diacylglycerol, fatty acyl CoA, fatty acyl carnitine, and liver triglycerides did not change with either treatment. PKC-theta activation during hyper-insulinemia decreased significantly following PPAR-alpha treatment.

Conclusion: PPAR-alpha agonist treatment increases palmitate oxidation and decreases PKC activity along with reduced insulin sensitivity in acute trauma, However, a direct link between these responses cannot be attributed to alterations in intracellular lipid concentrations.
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http://dx.doi.org/10.1186/1743-7075-4-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1868739PMC
April 2007

Insulin sensitivity and mitochondrial function are improved in children with burn injury during a randomized controlled trial of fenofibrate.

Ann Surg 2007 Feb;245(2):214-21

Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston 77555, USA.

Objective: To determine some of the mechanisms involved in insulin resistance immediately following burn trauma, and to determine the efficacy of PPAR-alpha agonism for alleviating insulin resistance in this population.

Summary Background Data: Hyperglycemia following trauma, especially burns, is well documented. However, the underlying insulin resistance is not well understood, and there are limited treatment options.

Methods: Twenty-one children 4 to 16 years of age with >40% total body surface area burns were enrolled in a double-blind, prospective, placebo-controlled randomized trial. Whole body and liver insulin sensitivity were assessed with a hyperinsulinemic-euglycemic clamp, and insulin signaling and mitochondrial function were measured in muscle biopsies taken before and after approximately 2 weeks of either placebo (PLA) or 5 mg/kg of PPAR-alpha agonist fenofibrate (FEN) treatment, within 3 weeks of injury.

Results: The change in average daily glucose concentrations was significant between groups after treatment (146 +/- 9 vs. 161 +/- 9 mg/dL PLA and 158 +/- 7 vs. 145 +/- 4 FEN; pretreatment vs. posttreatment; P = 0.004). Insulin-stimulated glucose uptake increased significantly in FEN (4.3 +/- 0.6 vs. 4.5 +/- 0.7 PLA and 5.2 +/- 0.5 vs. 7.6 +/- 0.6 mg/kg per minute FEN; pretreatment vs. posttreatment; P = 0.003). Insulin trended to suppress hepatic glucose release following fenofibrate treatment (P = 0.06). Maximal mitochondrial ATP production from pyruvate increased significantly after fenofibrate (P = 0.001) and was accompanied by maintained levels of cytochrome C oxidase and citrate synthase activity levels. Tyrosine phosphorylation of the insulin receptor and insulin receptor substrate-1 in response to insulin increased significantly following fenofibrate treatment (P = 0.04 for both).

Conclusions: Fenofibrate treatment started within 1 week postburn and continued for 2 weeks significantly decreased plasma glucose concentrations by improving insulin sensitivity, insulin signaling, and mitochondrial glucose oxidation. Fenofibrate may be a potential new therapeutic option for treating insulin resistance following severe burn injury.
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http://dx.doi.org/10.1097/01.sla.0000250409.51289.caDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1876998PMC
February 2007

Atrophy and impaired muscle protein synthesis during prolonged inactivity and stress.

J Clin Endocrinol Metab 2006 Dec 19;91(12):4836-41. Epub 2006 Sep 19.

Department of Surgery, The University of Texas Medical Branch, 301 University Boulevard, Galveston, Texas 77550, USA.

Context: We recently demonstrated that 28-d bed rest in healthy volunteers results in a moderate loss of lean leg mass and strength.

Objective: The objective of this study was to quantify changes in muscle protein kinetics, body composition, and strength during a clinical bed rest model reflecting both physical inactivity and the hormonal stress response to injury or illness.

Design: Muscle protein kinetics were calculated during a primed, continuous infusion (0.08 micromol/kg.min) of 13C6-phenylalanine on d 1 and 28 of bed rest.

Setting: The setting for this study was the General Clinical Research Center at the University of Texas Medical Branch.

Participants: Participants were healthy male volunteers (n = 6, 28 +/- 2 yr, 84 +/- 4 kg, 178 +/- 3 cm).

Intervention: During bed rest, hydrocortisone sodium succinate was administered iv (d 1 and 28) and orally (d 2-27) to reproduce plasma cortisol concentrations consistent with trauma or illness (approximately 22 microg/dl).

Main Outcome Measures: We hypothesized that inactivity and hypercortisolemia would reduce lean muscle mass, leg extension strength, and muscle protein synthesis.

Results: Volunteers experienced a 28.4 +/- 4.4% loss of leg extension strength (P = 0.012) and a 3-fold greater loss of lean leg mass (1.4 +/- 0.1 kg) (P = 0.004) compared with our previous bed rest-only model. Net protein catabolism was primarily due to a reduction in muscle protein synthesis [fractional synthesis rate, 0.081 +/- 0.004 (d 1) vs. 0.054 +/- 0.007%/h (d 28); P = 0.023]. There was no change in muscle protein breakdown.

Conclusion: Prolonged inactivity and hypercortisolemia represents a persistent catabolic stimulus that exacerbates strength and lean muscle loss via a chronic reduction in muscle protein synthesis.
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http://dx.doi.org/10.1210/jc.2006-0651DOI Listing
December 2006

Stimulation of net muscle protein synthesis by whey protein ingestion before and after exercise.

Am J Physiol Endocrinol Metab 2007 Jan 8;292(1):E71-6. Epub 2006 Aug 8.

The Univ. of Birmingham, School of Sport & Exercise Sciences, Edgbaston, Birmington B15 2TT, UK.

Timing of nutrient ingestion has been demonstrated to influence the anabolic response of muscle following exercise. Previously, we demonstrated that net amino acid uptake was greater when free essential amino acids plus carbohydrates were ingested before resistance exercise rather than following exercise. However, it is unclear if ingestion of whole proteins before exercise would stimulate a superior response compared with following exercise. This study was designed to examine the response of muscle protein balance to ingestion of whey proteins both before and following resistance exercise. Healthy volunteers were randomly assigned to one of two groups. A solution of whey proteins was consumed either immediately before exercise (PRE; n = 8) or immediately following exercise (POST; n = 9). Each subject performed 10 sets of 8 repetitions of leg extension exercise. Phenylalanine concentrations were measured in femoral arteriovenous samples to determine balance across the leg. Arterial amino acid concentrations were elevated by approximately 50%, and net amino acid balance switched from negative to positive following ingestion of proteins at either time. Amino acid uptake was not significantly different between PRE and POST when calculated from the beginning of exercise (67 +/- 22 and 27 +/- 10 for PRE and POST, respectively) or from the ingestion of each drink (60 +/- 17 and 63 +/- 15 for PRE and POST, respectively). Thus the response of net muscle protein balance to timing of intact protein ingestion does not respond as does that of the combination of free amino acids and carbohydrate.
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http://dx.doi.org/10.1152/ajpendo.00166.2006DOI Listing
January 2007

A high proportion of leucine is required for optimal stimulation of the rate of muscle protein synthesis by essential amino acids in the elderly.

Am J Physiol Endocrinol Metab 2006 Aug 28;291(2):E381-7. Epub 2006 Feb 28.

Department of Surgery, University of Texas Medical Branch, Galveston, Texas 77550, USA.

This study was designed to evaluate the effects of enriching an essential amino acid (EAA) mixture with leucine on muscle protein metabolism in elderly and young individuals. Four (2 elderly and 2 young) groups were studied before and after ingestion of 6.7 g of EAAs. EAAs were based on the composition of whey protein [26% leucine (26% Leu)] or were enriched in leucine [41% leucine (41% Leu)]. A primed, continuous infusion of L-[ring-2H5]phenylalanine was used together with vastus lateralis muscle biopsies and leg arteriovenous blood samples for the determinations of fractional synthetic rate (FSR) and balance of muscle protein. FSR increased following amino acid ingestion in both the 26% (basal: 0.048 +/- 0.005%/h; post-EAA: 0.063 +/- 0.007%/h) and the 41% (basal: 0.036 +/- 0.004%/h; post-EAA: 0.051 +/- 0.007%/h) Leu young groups (P < 0.05). In contrast, in the elderly, FSR did not increase following ingestion of 26% Leu EAA (basal: 0.044 +/- 0.003%/h; post-EAA: 0.049 +/- 0.006%/h; P > 0.05) but did increase following ingestion of 41% Leu EAA (basal: 0.038 +/- 0.007%/h; post-EAA: 0.056 +/- 0.008%/h; P < 0.05). Similar to the FSR responses, the mean response of muscle phenylalanine net balance, a reflection of muscle protein balance, was improved (P < 0.05) in all groups, with the exception of the 26% Leu elderly group. We conclude that increasing the proportion of leucine in a mixture of EAA can reverse an attenuated response of muscle protein synthesis in elderly but does not result in further stimulation of muscle protein synthesis in young subjects.
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http://dx.doi.org/10.1152/ajpendo.00488.2005DOI Listing
August 2006

Identification of factors contributing to hepatomegaly in severely burned children.

Shock 2005 Dec;24(6):523-8

Shriners Hospitals for Children, Galveston, Texas 77550, USA.

Hepatomegaly is a common postmortem observation in severely burned children, with the liver often tripling in size when compared with normal livers for age, weight, and sex. Lesions identified at autopsy include deposition of large and small fat droplets in the hepatocyte, congestion, centrilobular necrosis, and cholestasis. The present study was designed to identify the primary causes of hepatomegaly in severely burned children postmortem. For this purpose, 41 autopsies were reviewed and, when available, blood and tissue samples were studied. Histopathologic findings showed that large intrahepatocytic fat droplets within hepatocytes and cholestasis were important contributors to hepatomegaly. Liver density and wet/dry weight ratios significantly decreased with increasing liver size. Hepatocyte volume increased with increasing liver size (P < 0.001) as did total fat content (P < 0.001). The liver enzymes, alanine aminotransferase and aspartate aminotransferase, remained normal except within 5 to 10 days of injury and 5 to 10 days of death. Triglycerides made up 4% to 70% of the total fat, with the percentage of triglycerides increasing with the severity of hepatomegaly. Saturated fatty acids represented about 85% of the total fatty acids in normal-sized livers, whereas in the largest livers (400% of predicted), only 25% of the fatty acids were saturated. This study provides evidence that 85% to 90% of the hepatomegaly observed in severely burned children postmortem is associated with hepatocyte enlargement, which includes up to 19% intracellular fat. Increases in extracellular protein, intracellular glycogen, and fluid accumulation may make a minor contribution to postburn hepatomegaly.
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http://dx.doi.org/10.1097/01.shk.0000187981.78901.eeDOI Listing
December 2005

Aging is associated with diminished accretion of muscle proteins after the ingestion of a small bolus of essential amino acids.

Am J Clin Nutr 2005 Nov;82(5):1065-73

Department of Surgery, the University of Texas Medical Branch, Galveston, TX, USA.

Background: Previous evidence suggests that aging in healthy persons does not result in decreased incorporation of muscle proteins after a bolus ingestion of 15 g essential amino acids (EAAs).

Objective: We sought to examine whether ingestion of a smaller bolus of EAAs is associated with diminished accretion of muscle proteins in the elderly when compared with the young.

Design: Eleven elderly subjects (mean +/- SEM: 68 +/- 2 y) and 8 young control subjects (mean +/- SEM: 31 +/- 2 y) were studied in the postabsorptive state and for 3.5 h after a bolus ingestion of approximately 7 g EAAs. Muscle protein accretion and synthesis were measured with the femoral arteriovenous phenylalanine net balance technique during a constant infusion of L-[ring-(2)H5]phenylalanine.

Results: Similar to previous observations, no significant differences in the postabsorptive phenylalanine net balance were observed between the groups. However, the mean (+/-SEM) net phenylalanine uptake after EAA ingestion was significantly less in the elderly (9.9 +/- 3.7 mg/leg) than in the young (25.1 +/- 3.7 mg/leg; P < 0.05). The mean (+/-SEM) rate of disappearance of phenylalanine during the same period significantly increased above basal rates in the young (36 +/- 3 compared with 30 +/- 3 nmol x min(-1) x 100 mL leg volume(-1); P < 0.05) but not in the elderly (30 +/- 3 compared with 28 +/- 5 nmol x min(-1) x 100 mL leg volume(-1); P > 0.05).

Conclusions: These data indicate that aging results in a diminished accretion of muscle proteins after ingestion of a small dose of EAAs. These findings may have practical implications with respect to the amount of protein contained in supplements given to the elderly for enhancing the stimulation of muscle protein synthesis.
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http://dx.doi.org/10.1093/ajcn/82.5.1065DOI Listing
November 2005

Method for the determination of the arteriovenous muscle protein balance during non-steady-state blood and muscle amino acid concentrations.

Am J Physiol Endocrinol Metab 2005 Dec 9;289(6):E1064-70. Epub 2005 Aug 9.

Department of Surgery, Shriners Hospitals for Children-Galveston, and University of Texas Medical Branch, Galveston, TX 77550, USA.

We describe a method based on the traditional arteriovenous balance technique in conjunction with muscle biopsies for the determination of leg muscle protein balance during the nonsteady state in blood amino acid concentrations. Six young, healthy individuals were studied in the postabsorptive state (pre-Phe) and after a bolus ingestion of approximately 0.5 g phenylalanine (post-Phe). Post-Phe free phenylalanine concentrations in blood and muscle increased (P < 0.05), but the respective concentrations of the amino acid threonine did not change. The average post-Phe leg net balance (NB) for threonine decreased from basal (P < 0.05), but that for phenylalanine did not change. A volume of distribution for free phenylalanine in the leg was calculated based on the leg lean mass and the relative muscle water content and used to estimate the rate of accumulation of free phenylalanine in the leg. When the post-Phe NB for phenylalanine was corrected for the rate of accumulation of free phenylalanine in the leg, the post-Phe NB for phenylalanine decreased from basal (P < 0.05). This corrected value was not different (P > 0.05) from the value predicted for the phenylalanine NB based on the pre- and post-Phe NB responses for threonine. We conclude that the protein NB in non-steady-state blood phenylalanine concentrations can be determined from the arteriovenous phenylalanine NB by accounting for changes in free phenylalanine within its volume of distribution.
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http://dx.doi.org/10.1152/ajpendo.00141.2005DOI Listing
December 2005

The catabolic effects of prolonged inactivity and acute hypercortisolemia are offset by dietary supplementation.

J Clin Endocrinol Metab 2005 Mar 14;90(3):1453-9. Epub 2004 Dec 14.

Metabolism Unit, 815 Market Street, Galveston, Texas.

We compared the anabolic stimulus provided by an essential amino acid and carbohydrate (AA/CHO) supplement to a mixed clinical meal during bed rest (BR) and episodic hypercortisolemia ( approximately 24 microg.dl(-1)). In the experimental (EXP; n = 7) and control (CON; n = 6) groups, femoral arteriovenous blood samples and vastus lateralis biopsy samples were obtained during a primed constant infusion of l-[ring-(2)H(5)]phenylalanine and a 14-h infusion of hydrocortisone sodium succinate (60 microg.kg.h(-1)) before (pre-BR) and after (post-BR) 28 d of BR. Muscle protein kinetics were calculated during the postabsorptive state, for 2.5 h after ingestion of a meal and for 2.5 h after ingestion of an AA/CHO supplement (EXP) or placebo (CON). Postabsorptive net phenylalanine balance values were as follows: EXP, -35.14 +/- 2.93, and CON, -32.60 +/- 6.65 (pre-BR); and EXP, -32.91 +/- 5.67, and CON, -30.43 +/- 6.28 nmol phe.ml(-1).100 ml leg volume(-1) (post-BR). After AA/CHO supplementation, net phenylalanine balance improved to 33.51 +/- 8.06 (pre-BR) and 24.15 +/- 11.4 nmol phe.ml(-1).100 ml leg volume(-1) (post-BR), but remained negative after the meal. Cumulative 5.5-h mixed muscle fractional synthetic rate was greater in the EXP group pre-BR (EXP, 0.108 +/- 0.01, and CON, 0.073 +/- 0.04%.h(-1)) and post-BR (EXP, 0.111 +/- 0.015, and CON, 0.05 +/- 0.002%.h(-1)). Unlike a typical clinical meal, AA/CHO supplementation stimulated net muscle protein synthesis despite acute hypercortisolemia and prolonged inactivity.
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http://dx.doi.org/10.1210/jc.2004-1702DOI Listing
March 2005

Exogenous amino acids stimulate human muscle anabolism without interfering with the response to mixed meal ingestion.

Am J Physiol Endocrinol Metab 2005 Apr 30;288(4):E761-7. Epub 2004 Nov 30.

Department of Surgery, The University of Texas Medical Branch, Galveston, TX 77550, USA.

We sought to determine whether ingestion of a between-meal supplement containing 30 g of carbohydrate and 15 g of essential amino acids (CAA) altered the metabolic response to a nutritionally mixed meal in healthy, recreationally active male volunteers. A control group (CON; n = 6, 38 +/- 8 yr, 86 +/- 10 kg, 179 +/- 3 cm) received a liquid mixed meal [protein, 23.4 +/- 1.0 g (essential amino acids, 14.7 +/- 0.7 g); carbohydrate, 126.6 +/- 4.0 g; fat, 30.3 +/- 2.8 g] every 5 h (0830, 1330, 1830). The experimental group (SUP; n = 7, 36 +/- 10 yr, 87 +/- 12 kg, 180 +/- 3 cm) consumed the same meals but, in addition, were given CAA supplements (1100, 1600, 2100). Net phenylalanine balance (NB) and fractional synthetic rate (FSR) were calculated during a 16-h primed constant infusion of L-[ring-2H5]phenylalanine. Ingestion of a combination of CAA supplements and meals resulted in a greater mixed muscle FSR than ingestion of the meals alone (SUP, 0.099 +/- 0.008; CON, 0.076 +/- 0.005%/h; P < 0.05). Both groups experienced an improvement in NB after the morning (SUP, -2.2 +/- 3.3; CON, -1.5 +/- 3.5 nmol x min(-1) x 100 ml leg volume(-1)) and evening meals (SUP, -9.7 +/- 4.3; CON, -6.7 +/- 4.1 nmol x min(-1) x 100 ml leg volume(-1)). NB after CAA ingestion was significantly greater than after the meals, with values of 40.2 +/- 8.5 nmol x min(-1) x 100 ml leg volume(-1). These data indicate that CAA supplementation produces a greater anabolic effect than ingestion of intact protein but does not interfere with the normal metabolic response to a meal.
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http://dx.doi.org/10.1152/ajpendo.00291.2004DOI Listing
April 2005

Essential amino acid and carbohydrate supplementation ameliorates muscle protein loss in humans during 28 days bedrest.

J Clin Endocrinol Metab 2004 Sep;89(9):4351-8

Metabolism Unit, 815 Market Street, Galveston, Texas 77550, USA.

We determined whether essential amino acid and carbohydrate supplementation could offset the catabolic response to prolonged inactivity. Major outcome measures included mixed muscle fractional synthetic rate (FSR), phenylalanine net balance, lean leg mass, and leg extension strength. On d 1 and 28, vastus lateralis muscle biopsies and femoral arterio-venous blood samples were obtained during a primed constant infusion of l-[ring-(2)H(5)]phenylalanine. Net balance and FSR were calculated over 16 h, during which the control group (CON) received a nutritionally mixed meal every 5 h (0830, 1330, and 1830 h). The experimental group (EXP) also consumed 16.5 g essential amino acids and 30 g carbohydrate (1100, 1600, and 2100 h). The dietary regimen was maintained during bedrest. FSR was higher in the EXP group on d 1 (EXP, 0.099 +/- 0.008%/h; CON: 0.075 +/- 0.005%/h) and d 28 (EXP, 0.093 +/- 0.006%/h; CON, 0.055 +/- 0.007%/h). Lean leg mass was maintained throughout bedrest in the EXP group (+0.2 +/- 0.3 kg), but fell in the CON group (-0.4 +/- 0.1 kg). Strength loss was more pronounced in the CON group (EXP, -8.8 +/- 1.4 kg; CON, -17.8 +/- 4.4 kg). Essential amino acid and carbohydrate supplementation may represent a viable intervention for individuals at risk of sarcopenia due to immobility or prolonged bedrest.
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http://dx.doi.org/10.1210/jc.2003-032159DOI Listing
September 2004

Intramuscular and liver triglycerides are increased in the elderly.

J Clin Endocrinol Metab 2004 Aug;89(8):3864-71

Department of Surgery, The University of Texas Medical Branch and Shriners Hospitals for Children, Galveston, Texas 77550, USA.

Magnetic resonance spectroscopy studies have shown that intramyocellular lipids (IMCL) and liver fat (LFAT) levels vary with insulin sensitivity and obesity, which are common in the elderly. Thus, magnetic resonance spectroscopy was used to investigate the hypothesis that IMCL and LFAT are increased in the elderly. IMCL and LFAT in young (aged 20-32 yr) and elderly (aged 65-74 yr) were measured fasted, and glucose, insulin, total free fatty acids levels, and free fatty acids profiles were measured during a 2-h oral glucose tolerance test. Body fat percentage was determined with dual x-ray absorptiometry. The elderly had significantly greater IMCL (0.12 +/- 0.01 vs. 0.08 +/- 0.01, mean +/- sem; P = 0.01) and LFAT (0.28 +/- 0.06 vs. 0.08 +/- 0.01; P = 0.004; expressed as ratios to Intralipid standard) than the young. The elderly had increased insulin resistance as calculated by the Matsuda model compared with the young (5.1 +/- 0.9 vs. 9.9 +/- 1.4; P = 0.02). Regression analysis of all subjects indicated that the increases in IMCL and LFAT were correlated with insulin sensitivity, glycosylated hemoglobin, plasma lipids, and body fat. Furthermore, the correlation between insulin sensitivity and IMCL and LFAT remained significant, after accounting for the effect of body fat. Increases of IMCL and LFAT occur in elderly individuals and may be related to insulin resistance.
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http://dx.doi.org/10.1210/jc.2003-031986DOI Listing
August 2004

Effect of an amino acid, protein, and carbohydrate mixture on net muscle protein balance after resistance exercise.

Int J Sport Nutr Exerc Metab 2004 Jun;14(3):255-71

Metabolism Unit in the Department of Surgery at the Shriners Hospitals for Children/Galveston, University of Texas Medical Branch, 77550, USA.

This study tests the hypotheses that (a) a mixture of whey protein, amino acids (AA), and carbohydrates (CHO) stimulates net muscle protein synthesis to a greater extent than isoenergetic CHO alone after resistance exercise; and (b) that the stimulatory effect of a protein, AA, and CHO mixture will last beyond the 1st hour after intake. Eight subjects participated in 2 trials. In one (PAAC), they ingested 77.4 g CHO, 17.5 g whey protein, and 4.9 g AA 1 hr after resistance exercise. In the other (CON), 100 g CHO was ingested instead. They received a primed constant infusion of L-[2H5]-phenylalanine, and samples from femoral artery and vein, and biopsies from vastus lateralis were obtained. The area under the curve for net uptake of phenylalanine into muscle above pre-drink value was 128+/- 42 mg x leg(- 1) (PAAC) versus 32+/- 10 mg x leg (-1) (CON) for the 3 hr after the drink (p =.04). The net protein balance response to the mixture consisted of two components, one rapid immediate response, and a smaller delayed response about 90 min after drink, whereas in CON only a small delayed response was seen. We conclude that after resistance exercise, a mixture of whey protein, AA, and CHO stimulated muscle protein synthesis to a greater extent than isoenergetic CHO alone. Further, compared to previously reported findings, the addition of protein to an AA+ CHO mixture seems to extend the anabolic effect.
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http://dx.doi.org/10.1123/ijsnem.14.3.255DOI Listing
June 2004

Effect of carbohydrate intake on net muscle protein synthesis during recovery from resistance exercise.

J Appl Physiol (1985) 2004 Feb 31;96(2):674-8. Epub 2003 Oct 31.

Department of Surgery, Shriners Hospitals for Children-Galveston, University of Texas Medical Branch, Galveston, Texas 77550, USA.

The purpose of this study was to determine the effect of ingestion of 100 g of carbohydrates on net muscle protein balance (protein synthesis minus protein breakdown) after resistance exercise. Two groups of eight subjects performed a resistance exercise bout (10 sets of 8 repetitions of leg presses at 80% of 1-repetition maximum) before they rested in bed for 4 h. One group (CHO) received a drink consisting of 100 g of carbohydrates 1 h postexercise. The other group (Pla) received a noncaloric placebo drink. Leg amino acid metabolism was determined by infusion of 2H5- or 13C6-labeled phenylalanine, sampling from femoral artery and vein, and muscle biopsies from vastus lateralis. Drink intake did not affect arterial insulin concentration in Pla, whereas insulin increased several times after the drink in CHO (P < 0.05 vs. Pla). Arterial phenylalanine concentration fell slightly after the drink in CHO. Net muscle protein balance between synthesis and breakdown did not change in Pla, whereas it improved in CHO from -17 +/- 3 nmol.ml(-1).100 ml leg(-1) before drink to an average of -4 +/- 4 and 0 +/- 3 nmol.ml(-1).100 ml leg(-1) during the second and third hour after the drink, respectively (P < 0.05 vs. Pla during last hour). The improved net balance in CHO was due primarily to a progressive decrease in muscle protein breakdown. We conclude that ingestion of carbohydrates improved net leg protein balance after resistance exercise. However, the effect was minor and delayed compared with the previously reported effect of ingestion of amino acids.
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http://dx.doi.org/10.1152/japplphysiol.00333.2003DOI Listing
February 2004
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