Effects of obesity and severe lipodystrophy on oxidation and peroxidation of lipids: involvement of these molecules on inflammation and insulin resistance

• Grant number: 18/11156-5
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): July 01, 2018
• Effective date (End): June 30, 2020
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: William Tadeu Lara Festuccia
• Grantee: Adriano de Britto Chaves Filho
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 15/19530-5 - Involvement of the nutrient sensor mTOR in the development of obesity associated chronic metabolic diseases, AP.TEM

Abstract

Several lines of evidence suggest that obesity and lipodystrophy share common properties related to the buffering capacity of adipose tissue (AT) to adequately store fat, leading to redistribution and deposition of lipids in skeletal muscle, liver and pancreas (Snel et al., 2012). Since those organs and tissues do not possess the proper enzymatic machinery for fat storage, the local accumulation of lipids leads to development of inflammation, insulin resistance and hepatic steatosis. However, the nature and identity of the lipids exerting deleterious effects on metabolic homeostasis are still unclear. In the present proposal, we will test the hypothesis that oxidized lipids generated by radical and enzymatic pathways in AT and other tissues are important mediators of inflammation, insulin resistance and hepatic steatosis. For this purpose, we will characterize the lipidome and especially the oxidized lipid profile (oxylipidome), and identify the proteins modified by lipid aldehydes in AT, liver and serum of obese and lipodystrophic mice. The proposed analyses will further knowledge on the characterization of common molecular grounds between obesity and lipodystrophy as well as potentially help identifying targets for control and resolution of these metabolic dysfunctions.

Scientific publications

(4)

(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)

ANDRADE, MAYNARA L.; GILIO, GUSTAVO R.; PERANDINI, LUIZ A.; PEIXOTO, ALBERT S.; MORENO, MAYARA F.; CASTRO, ERIQUE; OLIVEIRA, TIAGO E.; VIEIRA, THAYNA S.; ORTIZ-SILVA, MILENE; THOMAZELLI, CAROLINE A.; et al. PAR gamma-induced upregulation of subcutaneous fat adiponectin secretion, glyceroneogenesis and BCAA oxidation requires mTORC1 activit. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, v. 1866, n. 8, AUG 2021. (15/19530-5, 17/17582-3, 13/07937-8, 19/01763-4, 17/12260-8, 15/22983-1, 16/23169-9, 19/04271-5, 15/13508-8, 18/11156-5, 19/17660-0, 17/23040-9, 17/17403-1)

ANDRADE, MAYNARA L.; GILIO, GUSTAVO R.; PERANDINI, LUIZ A.; PEIXOTO, ALBERT S.; MORENO, MAYARA F.; CASTRO, ERIQUE; OLIVEIRA, TIAGO E.; VIEIRA, THAYNA S.; ORTIZ-SILVA, MILENE; THOMAZELLI, CAROLINE A.; et al. PPAR gamma-induced upregulation of subcutaneous fat adiponectin secretion, glyceroneogenesis and BCAA oxidation requires mTORC1 activity. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, v. 1866, n. 8, p. 11-pg., 2021-05-19. (19/17660-0, 16/23169-9, 17/23040-9, 15/22983-1, 17/17403-1, 19/04271-5, 13/07937-8, 17/17582-3, 15/19530-5, 17/12260-8, 18/11156-5, 15/13508-8, 19/01763-4)

OLIVEIRA, TIAGO E.; CASTRO, ERIQUE; BELCHIOR, THIAGO; ANDRADE, MAYNARA L.; CHAVES-FILHO, ADRIANO B.; PEIXOTO, ALBERT S.; MORENO, MAYARA F.; ORTIZ-SILVA, MILENE; MOREIRA, RAFAEL J.; INAGUE, ALEX; et al. Fish Oil Protects Wild Type and Uncoupling Protein 1-Deficient Mice from Obesity and Glucose Intolerance by Increasing Energy Expenditure. MOLECULAR NUTRITION & FOOD RESEARCH, v. 63, n. 7, APR 2019. (15/19530-5, 17/17582-3, 16/07062-0, 17/12260-8, 15/22983-1, 16/23169-9, 15/13508-8, 18/11156-5, 17/23040-9)

CHAVES-FILHO, ADRIANO B.; PEIXOTO, ALBERT S.; CASTRO, ERIQUE; OLIVEIRA, TIAGO E.; PERANDINI, LUIZ A.; MOREIRA, RAFAEL J.; DA SILVA, RAILMARA P.; DA SILVA, BEATRIZ P.; MORETTI, EDUARDO H.; STEINER, ALEXANDRE A.; et al. Futile cycle of beta-oxidation and de novo lipogenesis are associated with essential fatty acids depletion in lipoatrophy. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, v. 1868, n. 3, p. 14-pg., 2022-12-20. (16/23169-9, 17/23040-9, 20/04159-8, 18/03418-0, 20/09399-7, 20/12969-0, 19/26473-9, 13/07937-8, 15/19530-5, 18/11156-5, 19/17660-0)