Tauroursodeoxycholic acid improves glucose tolerance and reduces adiposity in normal protein and malnourished mice fed a high-fat diet

Author(s)

Araujo, Thiago dos Reis ; Muniz, Mariana Roberta Rodrigues ; Alves, Bruna Lourenconi ; dos Santos, Lohanna Monali Barreto ; Bonfim, Maressa Fernandes ; da Silva Junior, Joel Alves ; Vettorazzi, Jean Franciesco ; Zoppi, Claudio Cesar ; Carneiro, Everardo Magalhaes

• Document type: Journal article
• Source: Food Research International; v. 156, p. 13-pg., 2022-06-01.

Abstract

Early childhood malnutrition may facilitate the onset of obesity and diabetes mellitus in adulthood which, when established, makes it more resistant to therapeutic interventions. The beneficial effects of tauroursodeoxycholic acid (TUDCA) in glucose homeostasis and body fat accumulation were analyzed in protein-restricted mice fed a high-fat diet (HFD). C57BL/6 mice were fed a control (14% protein [C]) or a protein-restricted (6% protein [R]) diet for 6 weeks. Afterward, mice received an HFD or not for 12 weeks (C mice fed an HFD [CH] and R mice fed an HFD [RH]). In the last 15 days of this period, half of the mice fed a HFD received i.p. PBS (groups CH and RH) or 300 mg/kg TUDCA (groups CHT and RHT). RH mice developed obesity, as demonstrated by the increase in fat accumulation, liver steatosis, and metabolic inflexibility. Additionally, showed glucose intolerance and insulin hypersecretion. TUDCA reduced adiposity and improve metabolic flexibility through increased HSL phosphorylation and CPT1 expression in eWAT and BAT, and reduced ectopic fat deposition by activating the AMPK/HSL pathway in the liver. Also, improved glucose tolerance and insulin sensitivity, normalizing insulin secretion by reducing GDH expression and increasing insulin peripheral sensitivity by greater expression of the IR13 in muscle and adipose tissue and reducing PEPCK liver expression. Our data indicate that TUDCA reduces global adiposity and improves glucose tolerance and insulin sensitivity in protein malnourished mice fed a HFD. Therefore, this is a possible strategy to reverse metabolic disorders in individuals with the double burden of malnutrition. (AU)

• FAPESP's process: 18/26080-4 - Characterization of molecular and functional mechanisms involved in endocrine-metabolic, cardiovascular and neural dysfunctions induced by the restriction of amino acids in vitro and in vivo: possible therapeutic role of bile acid TUDCA
• Grantee: Everardo Magalhães Carneiro
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 17/24851-0 - In vitro and in vivo analysis of the mechanism of action of tauroursodeoxycholic acid (TUDCA) on the mitochondrial function of pancreatic islets and insulin-responsive tissues submitted to amino acid restriction in association with fatty acids
• Grantee: Thiago dos Reis Araujo
• Support Opportunities: Scholarships in Brazil - Doctorate