Biomedicine & Pharmacotherapy (Oct 2021)

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

  • Tamires Duarte Afonso Serdan,
  • Laureane Nunes Masi,
  • Joice Naiara Bertaglia Pereira,
  • Luiz Eduardo Rodrigues,
  • Amanda Lins Alecrim,
  • Maria Vitoria Martins Scervino,
  • Vinicius Leonardo Sousa Diniz,
  • Alef Aragão Carneiro dos Santos,
  • Celso Pereira Batista Sousa Filho,
  • Tatiana Carolina Alba- Loureiro,
  • Gabriel Nasri Marzuca-Nassr,
  • Roberto Barbosa Bazotte,
  • Renata Gorjão,
  • Tania Cristina Pithon-Curi,
  • Rui Curi,
  • Sandro Massao Hirabara

Journal volume & issue
Vol. 142
p. 112019

Abstract

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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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