Publications by authors named "Renata Risi"

16 Publications

  • Page 1 of 1

Central obesity, smoking habit, and hypertension are associated with lower antibody titres in response to COVID-19 mRNA vaccine.

Diabetes Metab Res Rev 2021 May 6. Epub 2021 May 6.

Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, Rome, Italy.

Aims: To explore variables associated with the serological response following COVID-19 mRNA vaccine.

Methods: Eighty-six healthcare workers adhering to the vaccination campaign against COVID-19 were enrolled in January-February 2021. All subjects underwent two COVID-19 mRNA vaccine inoculations (Pfizer/BioNTech) separated by 3 weeks. Blood samples were collected before the 1st and 1-4 weeks after the second inoculation. Clinical history, demographics, and vaccine side effects were recorded. Baseline anthropometric parameters were measured, and body composition was performed through dual-energy-X-ray absorptiometry.

Results: Higher waist circumference was associated with lower antibody (Ab) titres (R = -0.324, p = 0.004); smokers had lower levels compared to non-smokers [1099 (1350) vs. 1921 (1375), p = 0.007], as well as hypertensive versus normotensive [650 ± 1192 vs. 1911 (1364), p = 0.001] and dyslipideamic compared to those with normal serum lipids [534 (972) vs 1872 (1406), p = 0.005]. Multivariate analysis showed that higher waist circumference, smoking, hypertension, and longer time elapsed since second vaccine inoculation were associated with lower Ab titres, independent of BMI, age. and gender.

Conclusions: Central obesity, hypertension, and smoking are associated with lower Ab titres following COVID-19 vaccination. Although it is currently impossible to determine whether lower SARS-CoV-2 Abs lead to higher likelihood of developing COVID-19, it is well-established that neutralizing antibodies correlate with protection against several viruses including SARS-CoV-2. Our findings, therefore, call for a vigilant approach, as subjects with central obesity, hypertension, and smoking could benefit from earlier vaccine boosters or different vaccine schedules.
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http://dx.doi.org/10.1002/dmrr.3465DOI Listing
May 2021

Beyond weight loss in nonalcoholic fatty liver disease: the role of carbohydrate restriction.

Curr Opin Clin Nutr Metab Care 2021 Jul;24(4):349-353

Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, Rome, Italy.

Purpose Of Review: The low fat diet (LFD) is currently the first choice to treat nonalcoholic fatty liver disease (NAFLD) alongside with physical activity. However, low carbohydrate diets (LCDs) and ketogenic diets have gained attention lately, thanks to their favourable impact in reducing intrahepatic triglyceride content. We therefore aimed at providing an update on recent evidence evaluating the hepatoprotective effects of such dietary interventions.

Recent Findings: Novel findings confirmed previous evidence by showing beneficial effects on liver fat content reduction for both LFDs and LCDs. The further restriction of carbohydrates to less than 50 g/day, usually leading to ketosis, confirmed to produce an improvement in NAFLD, with very low-calorie ketogenic diets possibly proving particularly beneficial thanks to the significant weight loss that can be obtained.

Summary: Most of the latest evidence shows that carbohydrate restriction plays a fundamental role in the modulation of lipid metabolism leading to similar efficacy in improving NAFLD compared with LFDs. The hepatoprotective role of carbohydrate restriction appears to be boosted when ketogenesis is induced, when the total calorie intake is extremely reduced, or, possibly, when dietary interventions have reduced content in free sugars, making such interventions valuable tools to deal with NAFLD.
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http://dx.doi.org/10.1097/MCO.0000000000000762DOI Listing
July 2021

Nickel Sensitivity Is Associated with GH-IGF1 Axis Impairment and Pituitary Abnormalities on MRI in Overweight and Obese Subjects.

Int J Mol Sci 2020 Dec 20;21(24). Epub 2020 Dec 20.

Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, Viale Regina Elena, 324, 00161 Rome, Italy.

Nickel (Ni) is a ubiquitous metal, the exposure of which is implied in the development of contact dermatitis (nickel allergic contact dermatitis (Ni-ACD)) and Systemic Ni Allergy Syndrome (SNAS), very common among overweight/obese patients. Preclinical studies have linked Ni exposure to abnormal production/release of Growth Hormone (GH), and we previously found an association between Ni-ACD/SNAS and GH-Insulin-like growth factor 1 (IGF1) axis dysregulation in obese individuals, altogether suggesting a role for this metal as a pituitary disruptor. We herein aimed to directly evaluate the pituitary gland in overweight/obese patients with signs/symptoms suggestive of Ni allergy, exploring the link with GH secretion; 859 subjects with overweight/obesity and suspected of Ni allergy underwent Ni patch tests. Among these, 106 were also suspected of GH deficiency (GHD) and underwent dynamic testing as well as magnetic resonance imaging for routine follow up of benign diseases or following GHD diagnosis. We report that subjects with Ni allergies show a greater GH-IGF1 axis impairment, a higher prevalence of Empty Sella (ES), a reduced pituitary volume and a higher normalized T2 pituitary intensity compared to nonallergic ones. We hypothesize that Ni may be detrimental to the pituitary gland, through increased inflammation, thus contributing to GH-IGF1 axis dysregulation.
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http://dx.doi.org/10.3390/ijms21249733DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766406PMC
December 2020

Very Low-Calorie Ketogenic Diets to Treat Patients With Obesity and Chronic Kidney Disease.

J Ren Nutr 2020 Oct 22. Epub 2020 Oct 22.

Section of Medical Pathophysiology, Department of Experimental Medicine, Food Science and Endocrinology, Sapienza University of Rome, Rome, Italy. Electronic address:

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http://dx.doi.org/10.1053/j.jrn.2020.09.001DOI Listing
October 2020

Liver disease in obesity and underweight: the two sides of the coin. A narrative review.

Eat Weight Disord 2020 Nov 4. Epub 2020 Nov 4.

Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, 00161, Rome, Italy.

Purpose: Malnutrition, whether characterized by not enough or too much nutrient intake, is detrimental to the liver. We herein provide a narrative literature revision relative to hepatic disease occurrence in over or undernourished subjects, to shed light on the paradox where both sides of malnutrition lead to similar liver dysfunction and fat accumulation.

Methods: Medline, EMBASE, and Cochrane Library were searched for publications up to July 2020. Articles discussing the association between both chronic and acute liver pathology and malnutrition were evaluated together with studies reporting the dietary intake in subjects affected by malnutrition.

Results: The association between overnutrition and non-alcoholic fatty liver disease (NAFLD) is well recognized, as the beneficial effects of calorie restriction and very low carbohydrate diets. Conversely, the link between undernutrition and liver injury is more complex and less understood. In developing countries, early exposure to nutrient deficiency leads to marasmus and kwashiorkor, accompanied by fatty liver, whereas in developed countries anorexia nervosa is a more common form of undernutrition, associated with liver injury. Weight gain in undernutrition is associated with liver function improvement, whereas no study on the impact of macronutrient distribution is available. We hypothesized a role for very low carbohydrate diets in the management of undernutrition derived liver pathology, in addition to the established one in overnutrition-related NAFLD.

Conclusions: Further studies are warranted to update the knowledge regarding undernutrition-related liver disease, and a specific interest should be paid to macronutrient distribution both in the context of refeeding and relative to its role in the development of hepatic complications of anorexia nervosa.

Level Of Evidence: Narrative review, Level V.
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http://dx.doi.org/10.1007/s40519-020-01060-wDOI Listing
November 2020

Current Evidence to Propose Different Food Supplements for Weight Loss: A Comprehensive Review.

Nutrients 2020 Sep 20;12(9). Epub 2020 Sep 20.

Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, 00161 Rome, Italy.

The use of food supplements for weight loss purposes has rapidly gained popularity as the prevalence of obesity increases. Navigating through the vast, often low quality, literature available is challenging, as is providing informed advice to those asking for it. Herein, we provide a comprehensive literature revision focusing on most currently marketed dietary supplements claimed to favor weight loss, classifying them by their purported mechanism of action. We conclude by proposing a combination of supplements most supported by current evidence, that leverages all mechanisms of action possibly leading to a synergistic effect and greater weight loss in the foreseen absence of adverse events. Further studies will be needed to confirm the weight loss and metabolic improvement that may be obtained through the use of the proposed combination.
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http://dx.doi.org/10.3390/nu12092873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551574PMC
September 2020

Is Growth Hormone Insufficiency the Missing Link Between Obesity, Male Gender, Age, and COVID-19 Severity?

Obesity (Silver Spring) 2020 11 25;28(11):2038-2039. Epub 2020 Sep 25.

Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, Viale Regina Elena, Rome, Italy.

Evidence has emerged regarding an increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with worse prognosis in elderly male patients with obesity, and blunted growth hormone (GH) secretion represents a feature of this population subgroup. Here, a comprehensive review of the possible links between GH-insulinlike growth factor 1 axis impairment and coronavirus disease 2019 (COVID-19) severity is offered. First, unequivocal evidence suggests that immune system dysregulation represents a key element in determining SARS-CoV-2 severity, as well as the association with adult-onset GH deficiency (GHD); notably, if GH is physiologically involved in the development and maintenance of the immune system, its pharmacological replacement in GHD patients seems to positively influence their inflammatory status. In addition, the impaired fibrinolysis associated with GHD may represent a further link between GH-insulin-like growth factor 1 axis impairment and COVID-19 severity, as it has been associated with both conditions. In conclusion, several sources of evidence have supported a relationship between GHD and COVID-19, and they also shed light upon potential beneficial effects of recombinant GH treatment on COVID-19 patients.
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http://dx.doi.org/10.1002/oby.23000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461181PMC
November 2020

Is obesity the missing link between COVID-19 severity and air pollution?

Environ Pollut 2020 Nov 3;266(Pt 3):115327. Epub 2020 Aug 3.

UNESCO Chair for Health Education and Sustainable Development Federico II University of Naples Corso Umberto I, 40 - 80138, Napoli, Centralino, Italy.

In the previous publication "Can atmospheric pollution be considered a co-factor in extremely high level of SARS-CoV-2 lethality in Northern Italy?" Conticini et al. hypothesized that the surplus of lethality of the novel SARS-CoV-2 in Northern Italy may be at least in part explained by the evidence of highest pollution reported in this area, as both severe COVID-19 and smog exposure are correlated to an innate immune system hyper-activation with subsequent lung inflammation and injury. Since this hypothesis alone does not fully explain why specific subgroups of patients are at major risk, we hypothesized that obesity may be one of the links between COVID-19 severity and high level of air pollution. First, obesity is a predisposing factor for SARS-Cov-2 infection and worse COVID-19 outcomes, and unequivocal evidence demonstrated that fat mass excess is independently associated with several pulmonary diseases and lung inflammation. Moreover, it has been shown that obesity may intensify the detrimental effects of air pollution on the lungs, and this is not surprising if we consider that these conditions share an excessive activation of the immune system and a lung inflammatory infiltrate. Finally, fat mass excess has also been speculated to be itself a consequence of air pollutants exposure, which has been proved to induce metabolic disruption and weight gain in murine models. In conclusion, although many variables must be taken into account in the analysis of the pandemic, our observations suggest that obesity may act as effect modifier of smog-induced lung-injury, and the concomitant presence of these two factors could better explain the higher virulence, faster spread and greater mortality of SARS-CoV-2 in Northern Italy compared to the rest of the country.
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http://dx.doi.org/10.1016/j.envpol.2020.115327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7397942PMC
November 2020

Visceral fat shows the strongest association with the need of intensive care in patients with COVID-19.

Metabolism 2020 10 23;111:154319. Epub 2020 Jul 23.

Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, 00161 Rome, Italy.

Background: Obesity was recently identified as a major risk factor for worse COVID-19 severity, especially among the young. The reason why its impact seems to be less pronounced in the elderly may be due to the concomitant presence of other comorbidities. However, all reports only focus on BMI, an indirect marker of body fat.

Aim: To explore the impact on COVID-19 severity of abdominal fat as a marker of body composition easily collected in patients undergoing a chest CT scan.

Methods: Patients included in this retrospective study were consecutively enrolled among those admitted to an Emergency Department in Rome, Italy, who tested positive for SARS-Cov-2 and underwent a chest CT scan in March 2020. Data were extracted from electronic medical records.

Results: 150 patients were included (64.7% male, mean age 64 ± 16 years). Visceral fat (VAT) was significantly higher in patients requiring intensive care (p = 0.032), together with age (p = 0.009), inflammation markers CRP and LDH (p < 0.0001, p = 0.003, respectively), and interstitial pneumonia severity as assessed by a Lung Severity Score (LSS) (p < 0.0001). Increasing age, lymphocytes, CRP, LDH, D-Dimer, LSS, total abdominal fat as well as VAT were found to have a significant univariate association with the need of intensive care. A multivariate analysis showed that LSS and VAT were independently associated with the need of intensive care (OR: 1.262; 95%CI: 1.0171-1.488; p = 0.005 and OR: 2.474; 95%CI: 1.017-6.019; p = 0.046, respectively).

Conclusions: VAT is a marker of worse clinical outcomes in patients with COVID-19. Given the exploratory nature of our study, further investigation is needed to confirm our findings and elucidate the mechanisms underlying such association.
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http://dx.doi.org/10.1016/j.metabol.2020.154319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377788PMC
October 2020

Baseline HOMA IR and Circulating FGF21 Levels Predict NAFLD Improvement in Patients Undergoing a Low Carbohydrate Dietary Intervention for Weight Loss: A Prospective Observational Pilot Study.

Nutrients 2020 Jul 18;12(7). Epub 2020 Jul 18.

Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, 00161 Rome, Italy.

Background: Non-alcoholic fatty liver disease (NAFLD) is a major cause of liver disease. Very low-calorie ketogenic diets (VLCKD) represent a feasible treatment as they induce profound weight loss and insulin resistance (IR) improvement. Despite the recognized benefits on NAFLD deriving from pharmacological administration of fibroblast growth factor 21 (FGF21), whose endogenous counterpart is a marker of liver injury, little is known about its physiology in humans.

Aim: To identify predictors of NAFLD improvement as reflected by the reduction of the non-invasive screening tool hepatic steatosis index (HSI) in obese patients undergoing a weight loss program.

Methods: Sixty-five obese patients underwent a 90-day dietary program consisting of a VLCKD followed by a hypocaloric low carbohydrate diet (LCD). Anthropometric parameters, body composition, and blood and urine chemistry were assessed.

Results: Unlike most parameters improving mainly during the VLCKD, the deepest HSI change was observed after the LCD ( = 0.02 and < 0.0001, respectively). Baseline HOMA-IR and serum FGF21 were found to be positive (R = 0.414, = 0009) and negative (R = 0.364, = 0.04) independent predictors of HSI reduction, respectively.

Conclusions: We suggest that patients with IR and NAFLD derive greater benefit from a VLCKD, and we propose a possible role of human FGF21 in mediating NAFLD amelioration following nutritional manipulation.
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http://dx.doi.org/10.3390/nu12072141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400878PMC
July 2020

Very-Low-Calorie Ketogenic Diets With Whey, Vegetable, or Animal Protein in Patients With Obesity: A Randomized Pilot Study.

J Clin Endocrinol Metab 2020 09;105(9)

Department of Experimental Medicine, University of Rome "La Sapienza," Rome, Italy.

Context: We compared the efficacy, safety, and effect of 45-day isocaloric very-low-calorie ketogenic diets (VLCKDs) incorporating whey, vegetable, or animal protein on the microbiota in patients with obesity and insulin resistance to test the hypothesis that protein source may modulate the response to VLCKD interventions.

Subjects And Methods: Forty-eight patients with obesity (19 males and 29 females, homeostatic model assessment (HOMA) index ≥ 2.5, aged 56.2 ± 6.1 years, body mass index [BMI] 35.9 ± 4.1 kg/m2) were randomly assigned to three 45-day isocaloric VLCKD regimens (≤800 kcal/day) containing whey, plant, or animal protein. Anthropometric indexes; blood and urine chemistry, including parameters of kidney, liver, glucose, and lipid metabolism; body composition; muscle strength; and taxonomic composition of the gut microbiome were assessed. Adverse events were also recorded.

Results: Body weight, BMI, blood pressure, waist circumference, HOMA index, insulin, and total and low-density lipoprotein cholesterol decreased in all patients. Patients who consumed whey protein had a more pronounced improvement in muscle strength. The markers of renal function worsened slightly in the animal protein group. A decrease in the relative abundance of Firmicutes and an increase in Bacteroidetes were observed after the consumption of VLCKDs. This pattern was less pronounced in patients consuming animal protein.

Conclusions: VLCKDs led to significant weight loss and a striking improvement in metabolic parameters over a 45-day period. VLCKDs based on whey or vegetable protein have a safer profile and result in a healthier microbiota composition than those containing animal proteins. VLCKDs incorporating whey protein are more effective in maintaining muscle performance.
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http://dx.doi.org/10.1210/clinem/dgaa336DOI Listing
September 2020

Obesity treatment within the Italian national healthcare system tertiary care centers: what can we learn?

Eat Weight Disord 2021 Apr 25;26(3):771-778. Epub 2020 May 25.

Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, Rome, Italy.

Introduction: The prevalence of obesity is soaring all over the world, and Italy is reaching the same pace. Similar to other countries, the Italian healthcare system counts on a three-tier model for obesity care, and each region has freedom in the implementation of guidelines. No national record is currently available to monitor the actual situation throughout the country.

Purpose: To provide a report of the current status on the availability of specialized public obesity care services in Italy.

Methods: Regional prevalence of obesity was extrapolated from publicly available data. Data on facilities for the management of obesity were retrieved from records provided by national scientific societies. Whenever possible, data was verified through online research and direct contact.

Results: We report a north-south and east-west gradient regarding the presence of obesity focused facilities, with an inverse correlation with the regional prevalence of obesity (R = 0.25, p = 0.03). Medical-oriented centers appear homogeneous in the multidisciplinary approach, the presence of a bariatric surgery division, the availability of support materials and groups, with no major difference on follow-up frequency. Surgery-oriented centers have a more capillary territorial distribution than the medically oriented, but not enough data was retrieved to provide a thorough description of their characteristics.

Conclusion: Obtaining a clear picture of the situation and providing consistent care across the country is a challenging task due to the decentralized organization of regions. We provide a first sketch, reporting that the model is applied unevenly, and we suggest feasible actions to improve the situation in our country and elsewhere.

Level Of Evidence: Level V, narrative review.
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http://dx.doi.org/10.1007/s40519-020-00936-1DOI Listing
April 2021

Letter to the Editor: "Our Response to COVID-19 as Endocrinologists and Diabetologists".

J Clin Endocrinol Metab 2020 07;105(7)

Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, Rome, Italy.

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http://dx.doi.org/10.1210/clinem/dgaa229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7197545PMC
July 2020

Obesity and SARS-CoV-2: A population to safeguard.

Diabetes Metab Res Rev 2020 Apr 21:e3325. Epub 2020 Apr 21.

Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, Rome, Italy.

Evidence has lately emerged regarding an increased risk of SARS-CoV-2 with worse prognosis in patients with obesity, especially among the young. Weight excess is a well-established respiratory disease risk factor, and the newly reported correlation is therefore unsurprising. The underlying pathophysiology is likely multi-stranded, ranging from complement system hyperactivation, increased Interleukin-6 secretion, chronic inflammation, presence of comorbidities such as diabetes and hypertension, and a possible local, detrimental effect within the lung. Further understanding the link between obesity and SARS-CoV-2 is crucial, as this could aid proper tailoring of immunomodulatory treatments, together with improving stratification among those possibly requiring critical care.
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http://dx.doi.org/10.1002/dmrr.3325DOI Listing
April 2020

Beneficial effects of the ketogenic diet on nonalcoholic fatty liver disease: A comprehensive review of the literature.

Obes Rev 2020 08 24;21(8):e13024. Epub 2020 Mar 24.

Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, Rome, Italy.

Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease, characterized by hepatic fat accumulation and possible development of inflammation, fibrosis, and cancer. The ketogenic diet (KD), with its drastic carbohydrate reduction, is a now popular weight loss intervention, despite safety concerns on a possible association with fatty liver. However, KDs were also reported to be beneficial on hepatic pathology, with ketone bodies recently proposed as effective modulators of inflammation and fibrosis. If the beneficial impact of weight loss on NAFLD is established, less is known on the effect of macronutrient distribution on such outcome. In a hypocaloric regimen, the latter seems not to be crucial, whereas at higher calorie intake, macronutrient ratio and, theoretically, ketosis, may become important. KDs could positively impact NAFLD for their very low carbohydrate content, and whether ketosis plays an additional role is unknown. Indeed, several mechanisms may directly link ketosis and NAFLD improvement, and elucidating these aspects would pave the way for new therapeutic strategies. We herein aimed at providing an accurate revision of current literature on KDs and NAFLD, focusing on clinical evidence, metabolic pathways involved, and strict categorization of dietary interventions.
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http://dx.doi.org/10.1111/obr.13024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7379247PMC
August 2020

Liver-derived FGF21 is essential for full adaptation to ketogenic diet but does not regulate glucose homeostasis.

Endocrine 2020 01 14;67(1):95-108. Epub 2019 Nov 14.

Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA.

Background: Fibroblast growth factor 21 (FGF21) is expressed in several metabolically active tissues, including liver, fat, and acinar pancreas, and has pleiotropic effects on metabolic homeostasis. The dominant source of FGF21 in the circulation is the liver.

Objective And Methods: To analyze the physiological functions of hepatic FGF21, we generated a hepatocyte-specific knockout model (LKO) by mating albumin-Cre mice with FGF21 flox/flox (fl/fl) mice and challenged it with different nutritional models.

Results: Mice fed a ketogenic diet typically show increased energy expenditure; this effect was attenuated in LKO mice. LKO on KD also developed hepatic pathology and altered hepatic lipid homeostasis. When evaluated using hyperinsulinemic-euglycemic clamps, glucose infusion rates, hepatic glucose production, and glucose uptake were similar between fl/fl and LKO DIO mice.

Conclusions: We conclude that liver-derived FGF21 is important for complete adaptation to ketosis but has a more limited role in the regulation of glycemic homeostasis.
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http://dx.doi.org/10.1007/s12020-019-02124-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948212PMC
January 2020