Effects of treatment wih fish oil on metabolic and endocrine dysfunction of adipocytes isolated from animals with metabolic syndrome

• Grant number: 17/08582-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): November 01, 2017
• Effective date (End): December 31, 2020
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Maria Isabel Cardoso Alonso-Vale
• Grantee: Roberta Dourado Cavalcante da Cunha de Sá
• Host Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil

Abstract

Overweight and obesity are associated with metabolic disorders such as insulin resistance, dyslipidemia, hypertension, among others, that led to metabolic syndrome. The prevalence of sedentary lifestyle and the transition to a high-calorie food, rich in saturated fat acids and simple sugars, has turned obesity into a global health problem. In fact, the increase in the prevalence of overweight is suggesting that behavioral and environmental components are mainly responsible for the epidemic, especially diet and physical inactivity. It is known that the energy imbalance between intake and expenditure of calories leads to abnormal or excessive fat accumulation. The distribution of white adipose tissue (WAT) is a major factor that lead to obesity. Obesity in turn, leads to the dysfunction of WAT, characterized by the hypertrophy of adipocytes with changes in its metabolic and endocrine activities, as well as changing in immune cells profile present in the stroma that alters the secretion of adipokines. The consumption of fish oil (FO) presents beneficial effects on changes caused by obesity. These effects are attributed to the high concentration of polyunsaturated É-3 fatty acids (É-3 FA) present in FO. The aim of this study is to investigate the effects of treatment with FO on metabolic and endocrine dysfunctions of adipocytes isolated from animals with obesity and metabolic syndrome, with emphasis on the differential response of subcutaneous and visceral adipose deposits, inguinal (ING) and retroperitoneal (RP) region, respectively. For this, C57BL / 6J (8 weeks) males mice will be induced to obesity by a high-fat diet (59% fat) for 8 weeks. After, these animals will be treated with FO (2 g / kg BW daily by gavage) for adicional 4 weeks. The body mass gain, food intake, adiposity, insulin tolerance test (ITT), glucose tolerance (GTT) and serum biochemical parameters (blood glucose and lipid profile) will be measured. The adipocytes isolated from inguinal subcutaneous tissue and retroperitoneal visceral, will be evaluated in terms of hypertrophy, expression of adipokines involved in the inflammatory response and insilin resistance (leptin, resistin, IL-6, adiponectin and TNF-± ), glucose uptake (in the presence and absence of insulin), expression of type 4 glucose transporter (GLUT4), expression of protein kinase B (AKT) (protein content and phosphorylation), synthesis of triacylglycerols from FA (by the oleate uptake and incorporation into TAG test and expression of LPL, GPAT, Lipin and DGAT enzymes, involved in this process), the synthesis of fatty acids from acetate (as well as the FAS and ACC1 enzymes expression, involved in this process) lipolysis (in the presence or absence of isoproterenol, as well the expression of ATGL, HSL and perilipin enzymes, involved in this process). Thus, the present study aims to contribute to the elucidation of the role of É-3 FA in the treatment of obesity, metabolic syndrome and metabolic and endocrine dysfunction of isolated adipocytes removed from mice induced to obesity by high fat diet.

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)

MENDES DE FARIAS, TALITA DA SILVA; CRUZ, MAYSA MARIANA; DA CUNHA DE SA, ROBERTA CAVALCANTE; SEVERI, ILENIA; PERUGINI, JESSICA; SENZACQUA, MARTINA; CERUTTI, SUZETE MARIA; GIORDANO, ANTONIO; CINTI, SAVERIO; CARDOSO ALONSO-VALE, MARIA ISABEL. Melatonin Supplementation Decreases Hypertrophic Obesity and Inflammation Induced by High-Fat Diet in Mice. FRONTIERS IN ENDOCRINOLOGY, v. 10, NOV 5 2019. (18/05485-6, 17/08582-0, 16/07638-9, 15/03554-2)

DA CUNHA DE SA, ROBERTA D. C.; CRUZ, MAYSA M.; DE FARIAS, TALITA M.; DA SILVA, VIVIANE S.; SIMAO, JUSSARA DE JESUS; TELLES, MONICA M.; ALONSO-VALE, MARIA ISABEL C.. Fish oil reverses metabolic syndrome, adipocyte dysfunction, and altered adipokines secretion triggered by high-fat diet-induced obesity. PHYSIOLOGICAL REPORTS, v. 8, n. 4, FEB 2020. (15/03554-2, 16/07638-9, 17/08582-0)

CAVALCANTE DA CUNHA DE SA, ROBERTA DOURADO; SIMAO, JUSSARA DE JESUS; DA SILVA, VIVIANE SIMOES; DE FARIAS, TALITA MENDES; CRUZ, MAYSA MARIANA; ANTRACO, VITOR JACO; ARMELIN-CORREA, LUCIA; ALONSO-VALE, MARIA ISABEL. Fish Oil Enriched in EPA, but Not in DHA, Reverses the Metabolic Syndrome and Adipocyte Dysfunction Induced by a High-Fat Diet. NUTRIENTS, v. 13, n. 3, MAR 2021. (17/08582-0, 18/05485-6)