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Molecular and functional mechanisms involved in the effects of TUDCA bile acid on perivascular adipose tissue in protein restriction

Grant number: 19/15164-5
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): October 01, 2019
Effective date (End): September 30, 2022
Field of knowledge:Biological Sciences - Physiology
Principal Investigator:Ana Paula Couto Davel
Grantee:Israelle Netto Freitas
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Malnutrition is a serious public health problem affecting mainly children in emerging countries. Protein restriction during development may culminate in cardiometabolic disorders in adulthood, with a higher risk to develop Type 2 Diabetes and Hypertension. Perivascular Adipose Tissue (PVAT) participates in the control of vascular homeostasis and physiologically presents an anticontractile and anti-inflammatory effect. It is suggested that PVAT dysfunction is involved in the vascular damage associated with Obesity, Hypertension and Diabetes, however studies evaluating the role of PVAT on protein restriction is absent in the literature. Recent studies raise the therapeutic potential of tauroursodeoxycholic bile acid (TUDCA) in metabolic disorders that affect the cardiovascular system, via attenuation of endoplasmic reticular stress (RE). PVAT is an important mediator of vascular ER in obese mice, an effect that is attenuated by TUDCA. Our research group have been demonstrated the beneficial effects of TUDCA in the secretion of insulin in obesity. In this study we hypothesized that treatment with TUDCA could be beneficial for vascular damage associated with protein restriction by mechanisms that improve the function of PVAT. We aimed to clarify the in vivo and in vitro effects of protein restriction in molecular and functional mechanisms of TUDCA on PVAT. Two methodological approaches will be used: 1) in vivo: mice will be submitted to the control or protein restriction diet, and treated or not with TUDCA (300 mg/kg/day; i.p.) or PBS. Thoracic aorta and resistance mesenteric arteries will be isolated with and without PVAT to assess vascular reactivity. In the PVAT, the production of nitric oxide (NO), Reactive Oxygen Species (EROS), adipokines and ER markers and morphology will be evaluated; 2) in vitro: adipocytes derived from PVAT will be submitted to a control or amino acid restriction medium, in the presence or absence of TUDCA (200 ¼M), and then cell viability, NO production, EROS, adipokines and markers of ER, and the signaling pathways involved will be evaluated. (AU)