The role of hyperinsulinemia on SIRT activity, PPAr-y acetylation and UCP expression in adipose tissue.

• Grant number: 16/23251-7
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: April 05, 2017
• End date: April 04, 2018
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: José Rodrigo Pauli
• Grantee: José Diego Botezelli
• Supervisor: James D. Johnson
• Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil
• Institution abroad: University of British Columbia, Vancouver (UBC), Canada
• Associated to the scholarship: 13/20293-2 - Effects of endurance and strength exercises on the glucose uptake pathways in knockout heterozygous GLUT4 mice, BP.PD

Abstract

Obesity is a major independent risk factor for many metabolic diseases. In the last few decades, pharmacological treatments have failed in prevent the progression of this disease. In 2007, the discovery of conserved brown adipose tissue (BAT) in adult humans brought new perspectives against the excessive weight. This tissue has increased levels of mitochondria expressing uncouple proteins (UCP). UCPs can use the excessive glucose or triglycerides to produce heat, preventing the adipose tissue hypertrophy. The idea of burn the excessive energy activating the BAT is promisor and much progress has been made ever since. Researchers have found that a group of proteins named Sirtuin (SIRT) have the ability to activate genes usually expressed in BAT (brown genes) in the white adipose tissue (WAT). Sirtuins de-acetylate the peroxisome proliferator-activated receptor gamma (PPAR-³) leading the formation of the complex PPAR-³/PRDM16 responsible for cell reprogramming. The highly conserved hormone insulin, seems to regulate both Sirtuin and PPAR activation leading to changes in adipose tissue fate. To test this hypothesis, we will investigate the role of insulin hypersecretion in diet-induced obesity in the Sirtuin activation, PPAR-³ acetylation and UCP expression in the white adipose tissue. The results presented by this research may provide a better understanding of the mechanisms connecting the hyperinsulinemia and reduced energy expenditure.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MYETTE-COTE, ETIENNE; DURRER, CODY; NEUDORF, HELENA; BAMMERT, TYLER D.; BOTEZELLI, JOSE DIEGO; JOHNSON, JAMES D.; DESOUZA, CHRISTOPHER A.; LITTLE, JONATHAN P.. The effect of a short-term low-carbohydrate, high-fat diet with or without postmeal walks on glycemic control and inflammation in type 2 diabetes: a randomized trial. AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, v. 315, n. 6, p. R1210-R1219, DEC 2018. (16/23251-7)

BOTEZELLI, JOSE DIEGO; OVERBY, PETER; LINDO, LORENZO; WANG, SU; HAIDA, OBELIA; LIM, GARETH E.; TEMPLEMAN, NICOLE M.; PAULI, JOSE RODRIGO; JOHNSON, JAMES D.. Adipose depot-specific upregulation of Ucp1 or mitochondrial oxidative complex proteins are early consequences of genetic insulin reduction in mice. AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, v. 319, n. 3, p. 11-pg., 2020-09-01. (16/23251-7)