Key result
Diet-induced obese and lean genetic rats exhibit impaired BAT function and tissue whitening.
Why the study?
Differences between obese and lean models of insulin resistance and the mechanisms of brown adipose tissue metabolism and dysfunction in these settings remained unclear.
Both genetic and diet-induced models of insulin resistance exhibit impaired brown adipose tissue function and evidence of a whitening process, with distinct metabolic and transcriptomic profiles.
BAT impairment in obese/diabetic rat models should not guide human care; leaves open whether targeting BAT whitening offers therapeutic benefit.
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 β3-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.
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Serdan et al. (2021) studied Insulin resistance and obesity (n=65). High-fat diet, high-fat/high-sugar diet, or genetic insulin resistance (Goto-Kakizaki) vs. High-carbohydrate diet (control) was evaluated on Brown adipose tissue (BAT) glucose uptake and morphological changes. Both diet-induced obese Wistar rats and lean genetic Goto-Kakizaki rats exhibited impaired brown adipose tissue function, decreased glucose uptake, and evidence of a whitening process.
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