Publications by authors named "Todd Tolentino"

3 Publications

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On the potential role of globins in brown adipose tissue: a novel conceptual model and studies in myoglobin knockout mice.

Am J Physiol Endocrinol Metab 2021 May 10. Epub 2021 May 10.

Arkansas Children's Nutrition Center, Little Rock, AR, USA.

Myoglobin (Mb) regulates O bioavailability in muscle and heart as partial pressure of O (pO) drops with increased tissue workload. Globin proteins also modulate cellular NO pools, "scavenging" NO at higher pO and converting NO to NO as pO falls. Myoglobin binding of fatty acids may also signal a role in fat metabolism. Interestingly, Mb is expressed in brown adipose tissue (BAT), but its function is unknown. Herein, we present a new conceptual model that proposes links between BAT thermogenic activation, concurrently reduced pO, and NO pools regulated by deoxy/oxy-globin toggling and xanthine oxidoreductase (XOR). We describe the effect of Mb knockout (Mb) on BAT phenotype (lipid droplets, mitochondrial markers uncoupling protein 1 [UCP1] and cytochrome C oxidase 4 [Cox4], transcriptomics) in male and female mice fed a high fat diet (HFD, 45% of energy, ~13 wk), and examine Mb expression during brown adipocyte differentiation. Interscapular BAT weights did not differ by genotype, but there was a higher prevalence of mid-large sized droplets in Mb. COX4 protein expression was significantly reduced in Mb BAT, and a suite of metabolic/NO/stress/hypoxia transcripts were lower. All of these Mb-associated differences were most apparent in females. The new conceptual model, and results derived from Mb mice, suggest a role for Mb in BAT metabolic regulation, in part through sexually dimorphic systems and NO signaling. This possibility requires further validation in light of significant mouse-to-mouse variability of BAT Mb mRNA and protein abundances in wildtype mice and lower expression relative to muscle and heart.
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http://dx.doi.org/10.1152/ajpendo.00662.2020DOI Listing
May 2021

Metabolic physiology and skeletal muscle phenotypes in male and female myoglobin knockout mice.

Am J Physiol Endocrinol Metab 2021 May 10. Epub 2021 May 10.

Arkansas Children's Nutrition Center, Little Rock, AR, USA.

Myoglobin (Mb) is a regulator of O bioavailability in type I muscle and heart, at least when tissue O levels drop. Mb also plays a role in regulating cellular NO pools. Robust binding of long-chain fatty acids and long-chain acylcarnitines to Mb, and enhanced glucose metabolism in hearts of Mb knockout (KO) mice, suggests additional roles in muscle intermediary metabolism and fuel selection. To evaluate this hypothesis, we measured energy expenditure (EE), respiratory exchange ratio (RER), body weight gain and adiposity, glucose tolerance and insulin sensitivity in Mb knockout (Mb) and wildtype (WT) mice challenged with a high fat diet (HFD, 45% of calories). In males (n=10/genotype) and females (n=9/genotype) aged 5-6, 11-12, and 17-18 wk, there were no genotype effects on RER, EE, or food intake. RER and EE during cold (10˚C, 72 h), and glucose and insulin tolerance, were not different compared to within-sex WT controls. At ~18 and ~19 wk of age, female Mb adiposity was ~42-48% higher vs. WT females (p=0.1). Transcriptomics analyses (whole gastrocnemius, soleus) revealed few consistent changes, with the notable exception of a 20% drop in soleus transferrin receptor (Tfrc) mRNA. Capillarity indices were significantly increased in Mb, specifically in Mb-rich soleus and deep gastrocnemius. The results indicate that Mb loss does not have a major impact on whole-body glucose homeostasis, EE, RER, or response to a cold challenge in mice. However, the greater adiposity in female Mb mice indicates a sex-specific effect of Mb KO on fat storage and feed efficiency.
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http://dx.doi.org/10.1152/ajpendo.00624.2020DOI Listing
May 2021

Coupling of energy intake and energy expenditure across a temperature spectrum: impact of diet-induced obesity in mice.

Am J Physiol Endocrinol Metab 2020 09 21;319(3):E472-E484. Epub 2020 Jul 21.

Arkansas Children's Nutrition Center, Little Rock, Arkansas.

Obesity and its metabolic sequelae are implicated in dysfunction of the somatosensory, sympathetic, and hypothalamic systems. Because these systems contribute to integrative regulation of energy expenditure (EE) and energy intake (EI) in response to ambient temperature (T) changes, we hypothesized that diet-induced obesity (DIO) disrupts T-associated EE-EI coupling. C57BL/6N male mice were fed a high-fat diet (HFD; 45% kcal) or low-fat diet (LFD; 10% kcal) for ∼9.5 wk; HFD mice were then split into body weight (BWT) quartiles ( = 8 each) to study DIO-low gainers (Q1) versus -high gainers (Q4). EI and indirect calorimetry (IC) were measured over 3 days each at 10°C, 20°C, and 30°C. Responses did not differ between LFD, Q1, and Q4; EI and BWT-adjusted EE increased rapidly when transitioning toward 20°C and 10°C. In all groups, EI at 30°C was not reduced despite lower EE, resulting in positive energy balance and respiratory exchange ratios consistent with increased de novo lipogenesis, energy storage, and relative hyperphagia. We conclude that ) systems controlling T-dependent acute EI/EE coupling remained intact in obese mice and ) rapid coupling of EI/EE at cooler temperatures is an important adaptation to maintain energy stores and defend body temperature, but less critical at thermoneutrality. A post hoc analysis using digestible EI plus IC-calculated EE suggests that standard IC assumptions for EE calculation require further validation in the setting of DIO. The experimental paradigm provides a platform to query the hypothalamic, somatosensory, and sympathetic mechanisms that drive T-associated EI/EE coupling.
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http://dx.doi.org/10.1152/ajpendo.00041.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509245PMC
September 2020