Impaired brown adipose tissue is differentially modulated in insulin-resistant obese wistar and type 2 diabetic Goto-Kakizaki rats.

Brown adipose tissue (BAT) is a potential target to treat obesity and diabetes, dissipating energy as heat. Type 2 diabetes (T2D) has been associated with obesogenic diets; however, T2D was also reported in lean individuals to be associated with genetic factors. We aimed to investigate the differences between obese and lean models of insulin resistance (IR) and elucidate the mechanism associated with BAT metabolism and dysfunction in different IR animal models: a genetic model (lean GK rats) and obese models (diet-induced obese Wistar rats) at 8 weeks of age fed a high-carbohydrate (HC), high-fat (HF) diet, or high-fat and high-sugar (HFHS) diet for 8 weeks. At 15 weeks of age, BAT glucose uptake was evaluated by 18F-FDG PET under basal (saline administration) or stimulated condition (CL316,243, a selective ß3-AR agonist). After CL316, 243 administrations, GK animals showed decreased glucose uptake compared to HC animals. At 16 weeks of age, the animals were euthanized, and the interscapular BAT was dissected for analysis. Histological analyses showed lower cell density in GK rats and higher adipocyte area compared to all groups, followed by HFHS and HF compared to HC. HFHS showed a decreased batokine FGF21 protein level compared to all groups. However, GK animals showed increased expression of genes involved in fatty acid oxidation (CPT1 and CPT2), BAT metabolism (Sirt1 and Pgc1-α), and obesogenic genes (leptin and PAI-1) but decreased gene expression of glucose transporter 1 (GLUT-1) compared to other groups. Our data suggest impaired BAT function in obese Wistar and GK rats, with evidence of a whitening process in these animals.

Glutamine supplementation versus functional overload in extensor digitorum longus muscle hypertrophy

Background Glutamine levels directly associate with total protein content in cultured skeletal muscle cells, whereas glutamine supplementation enhances skeletal muscle mass in catabolic experimental conditions. Methods We compared the effect of glutamine administration on Extensor Digitorum Longus muscle (EDL) weight, fiber cross-sectional area (CSA), contractile activity, and protein metabolism signaling with a functional overload-induced skeletal muscle hypertrophy protocol. Results Glutamine supplementation raised the predominance of EDL muscle fibers with CSA between 1001 and 2000 μm2 (49.7 %), the p-4E-BP1/total 4E-BP1 ratio, and the effect of overload on resistance to fatigue. The proportion of the EDL muscle fiber CSA distribution for the combination of both treatments was similar to that induced by overload or glutamine separately; 54.3 % muscle fibers with CSA between 1001 and 2000 μm². Glutamine supplementation did not markedly affect the changes induced by overload on protein synthesis signaling pathways, except for a further increase of the p-4E-BP1/total 4E-BP1 ratio. Conclusions The effect of glutamine on EDL muscle fiber CSA distribution and protein synthesis signaling mimicked the response to overload. The association of glutamine and overload induced EDL muscle hypertrophy further increased the resistance to fatigue.