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

Author(s):Show less -

Serdan, Tamires Duarte Afonso ^[1] ; Masi, Laureane Nunes ^[1] ; Pereira, Joice Naiara Bertaglia ^[1] ; Rodrigues, Luiz Eduardo ^[1] ; Alecrim, Amanda Lins ^[1] ; Scervino, Maria Vitoria Martins ^[1] ; Diniz, Vinicius Leonardo Sousa ^[1] ; dos Santos, Alef Aragao Carneiro ^[1] ; Sousa Filho, Celso Pereira Batista ^[1] ; Alba-Loureiro, Tatiana Carolina ^[1] ; Marzuca-Nassr, Gabriel Nasri ^[2] ; Bazotte, Roberto Barbosa ^[3] ; Gorjao, Renata ^[1] ; Pithon-Curi, Tania Cristina ^[1] ; Curi, Rui ^[1] ; Hirabara, Sandro Massao ^[1]

Affiliation

^[1] Univ Cruzeiro Sul, Interdisciplinary Postgrad Program Hlth Sci, Sao Paulo - Brazil

^[2] Univ La Frontera, Fac Med, Dept Internal Med, Temuco - Chile

^[3] Univ Estadual Maringa, Dept Pharmacol & Therapeut, Maringa, Parana - Brazil

• Document type: Journal article
• Source: BIOMEDICINE & PHARMACOTHERAPY; v. 142, OCT 2021.
• Web of Science Citations: 0

Abstract

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 beta 3-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-alpha), 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 (AU)

• FAPESP's process: 18/09868-7 - Cellular and molecular mechanisms of insulin resistance and inflammation in obese Wistar rats and lean Goto-Kakizaki rats: causes and associations with diet and physical exercise
• Grantee: Rui Curi
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 18/18815-4 - Brite/beige adipocytes: a potential tool against obesity and diabetes?
• Grantee: Tamires Duarte Afonso Serdan
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• FAPESP's process: 19/25936-5 - Research Contingency Fund for Institutional Infraestructure of the Cruzeiro do Sul University - 2019
• Grantee: Tania Cristina Pithon Curi
• Support Opportunities: Research Grants - Technical Reserve for Institutional Research Infrastructure
• FAPESP's process: 16/14529-1 - Metabolism of the brown adipose tissue in animal models of insulin resistance: Goto-Kakizaki and obese Wistar rats
• Grantee: Tamires Duarte Afonso Serdan
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)