Role of adipose tissue in the development of obesity and associated co-morbidities: investigation of molecular mechanism and search for alternative therapies

• Grant number: 09/15354-7
• Support Opportunities: Research Grants - Young Investigators Grants
• Duration: July 01, 2010 - June 30, 2014
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: William Tadeu Lara Festuccia
• Grantee: William Tadeu Lara Festuccia
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated grant(s): 13/50394-5 - Polyphenol enriched fruit extracts as alternative therapy against adipocyte dysfunctions associated with obesity and metabolic disorders, AP.R
• Associated scholarship(s): 13/15825-5 - SEARCHING NEW THERAPIES FOR INSULIN RESISTANCE: DEVELOPMENT OF A PLATFORM FOR DRUG SCREENING AND PRECLINICAL IN VIVO ASSAY, BP.PD; 12/25317-4 - Involvement of mTOR complex 1 and 2 in secretory control of lipid and protein inflammatory mediators by adipocytes in obesity and insulin resistance conditions., BP.PD; 11/13563-8 - Obesogenic diet and inflammatory process in the brainstem and its interaction with the autonomic nervous system and the arterial pressure, BP.DR; + associated scholarships 11/10783-7 - mTOR complex 1 involvement in the control of macrophage function in the chronic inflammatory response associated with obesity and insulin resistance, BP.DR; 11/14172-2 - Involvement of PPARgamma in development of low-intensity chronic inflammation and insulin resistance associated with obesity. Participation in the actions of omega-3 fatty acids., BP.DR; 11/03972-8 - Modulation of transcriptional activity of nuclear receptors PPAR-gamma, GR and TR-alpha by mTORC1 during and after adipogenesis, BP.DR; 10/19018-9 - Inter-relationships among insulin resistance, hypothalamic dysfunction, sympathetic hyperactivity and arterial hypertension induced by high fat, high sucrose diet., BP.IC; 10/10909-8 - Role of adipose tissue in the development of obesity and associated co-morbidities: investigation of molecular mechanism and search for alternative therapies, BP.JP - associated scholarships

Abstract

The exponential growth of obesity in the world is associated with a marked increase in the prevalence of several morbidities directly associated with excessive adiposity as Type 2 Diabetes (T2D), Metabolic Syndrome (MS), atherosclerosis, hypertension, stroke, hepatic steatosis and some types of cancer. The main goal of the current research proposal is to investigate the molecular mechanisms linking obesity and the development of T2D and MS, focusing on the role of adipose tissue, through the cross-talking with central nervous system, liver and heart, as the main origin of these complications (adipocentric theory). More specifically, the current research proposal consists of three integrated research programs that will investigate: 1- the role of sympathetic nervous system in the control of adipose tissue insulin sensitivity, inflammation, metabolic and endocrine functions; 2- the mechanism underlying the modulation of liver and adipose tissue transcriptional activity of PPARs and lipid and glucose metabolism by mTOR; and 3- the mechanisms involved in the fat redistribution, heart remodeling and positive energy balance induced by PPARgamma activation and the contribution of adiponectin to these effects. (AU)

Scientific publications

(13)

(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)

BIRSOY, KIVANC; FESTUCCIA, WILLIAM T.; LAPLANTE, MATHIEU. A comparative perspective on lipid storage in animals. Journal of Cell Science, v. 126, n. 7, p. 1541-1552, APR 1 2013. (09/15354-7)

LAPLANTE‚ M.; HORVAT‚ S.; FESTUCCIA‚ W.T.; BIRSOY‚ K.; PREVORSEK‚ Z.; EFEYAN‚ A.; SABATINI‚ D.M.. DEPTOR Cell-Autonomously Promotes Adipogenesis, and Its Expression Is Associated with Obesity. Cell Metabolism, v. 16, n. 2, p. 202-212, 2012. (10/10909-8, 09/15354-7)

CHIMIN, PATRICIA; ANDRADE, MAYNARA L.; BELCHIOR, THIAGO; PASCHOAL, VIVIAN A.; MAGDALON, JULIANA; YAMASHITA, ALEX S.; CASTRO, ERIQUE; CASTOLDI, ANGELA; CHAVES-FILHO, ADRIANO B.; YOSHINAGA, MARCOS Y.; et al. Adipocyte mTORC1 deficiency promotes adipose tissue inflammation and NLRP3 inflammasome activation via oxidative stress and de novo ceramide synthesis. Journal of Lipid Research, v. 58, n. 9, p. 1797-1807, SEP 2017. (12/25317-4, 15/19530-5, 12/02270-2, 15/13508-8, 09/15354-7)

BLANCHARD, P. G.; TURCOTTE, V.; COTE, M.; GELINAS, Y.; NILSSON, S.; OLIVECRONA, G.; DESHAIES, Y.; FESTUCCIA, W. T.. Peroxisome proliferator-activated receptor activation favours selective subcutaneous lipid deposition by coordinately regulating lipoprotein lipase modulators, fatty acid transporters and lipogenic enzymes. ACTA PHYSIOLOGICA, v. 217, n. 3, p. 227-239, JUL 2016. (09/15354-7)

CHAAR, LAIALI J.; COELHO, ALINE; SILVA, NATALIA M.; FESTUCCIA, WILLIAM L.; ANTUNES, VAGNER R.. High-fat diet-induced hypertension and autonomic imbalance are associated with an upregulation of CART in the dorsomedial hypothalamus of mice. PHYSIOLOGICAL REPORTS, v. 4, n. 11, JUN 2016. (13/06206-0, 11/13563-8, 09/15354-7, 10/19018-9, 15/19530-5)

PASCHOAL, VIVIAN A.; AMANO, MARIANE T.; BELCHIOR, THIAGO; MAGDALON, JULIANA; CHIMIN, PATRICIA; ANDRADE, MAYNARA L.; ORTIZ-SILVA, MILENE; CASTRO, ERIQUE; YAMASHITA, ALEX S.; ROSA NETO, JOSE CESAR; et al. mTORC1 inhibition with rapamycin exacerbates adipose tissue inflammation in obese mice and dissociates macrophage phenotype from function. Immunobiology, v. 222, n. 2, p. 261-271, FEB 2017. (15/19530-5, 12/02270-2, 11/10783-7, 09/15354-7)

BELCHIOR, THIAGO; PASCHOAL, VIVIAN A.; MAGDALON, JULIANA; CHIMIN, PATRICIA; FARIAS, TALITA M.; CHAVES-FILHO, ADRIANO B.; GORJAO, RENATA; ST-PIERRE, PHILIPPE; MIYAMOTO, SAYURI; KANG, JING X.; et al. Omega-3 fatty acids protect from diet-induced obesity, glucose intolerance, and adipose tissue inflammation through PPAR gamma-dependent and PPAR gamma-independent actions. MOLECULAR NUTRITION & FOOD RESEARCH, v. 59, n. 5, p. 957-967, MAY 2015. (11/14172-2, 09/15354-7)

FESTUCCIA, WILLIAM T.; BLANCHARD, PIERRE-GILLES; OLIVEIRA, THIAGO B.; MAGDALON, JULIANA; PASCHOAL, VIVIAN A.; RICHARD, DENIS; DESHAIES, YVES. PPAR gamma activation attenuates cold-induced upregulation of thyroid status and brown adipose tissue PGC-1 alpha and D2. AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, v. 303, n. 12, p. R1277-R1285, DEC 2012. (10/10909-8, 09/15354-7)

BOLSONI-LOPES, ANDRESSA; FESTUCCIA, WILLIAM T.; FARIAS, TALITA S. M.; CHIMIN, PATRICIA; TORRES-LEAL, FRANCISCO L.; DEROGIS, PRISCILLA B. M.; DE ANDRADE, PAULA B.; MIYAMOTO, SAYURI; LIMA, FABIO B.; CURI, RUI; et al. Palmitoleic acid (n-7) increases white adipocyte lipolysis and lipase content in a PPAR alpha-dependent manner. AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, v. 305, n. 9, p. E1093-E1102, NOV 2013. (10/10909-8, 11/51627-8, 09/15354-7)

BLANCHARD, PIERRE-GILLES; FESTUCCIA, WILLIAM T.; HOUDE, VANESSA P.; ST-PIERRE, PHILIPPE; BRULE, SOPHIE; TURCOTTE, VERONIQUE; COTE, MARIE; BELLMANN, KERSTIN; MARETTE, ANDRE; DESHAIES, YVES. Major involvement of mTOR in the PPAR gamma-induced stimulation of adipose tissue lipid uptake and fat accretion. Journal of Lipid Research, v. 53, n. 6, p. 1117-1125, JUN 2012. (10/10909-8, 09/15354-7)

FESTUCCIA, WILLIAM T.; BLANCHARD, PIERRE-GILLES; BELCHIOR, THIAGO; CHIMIN, PATRICIA; PASCHOAL, VIVIAN A.; MAGDALON, JULIANA; HIRABARA, SANDRO M.; SIMOES, DANIEL; ST-PIERRE, PHILIPPE; CARPINELLI, ANGELO; et al. PPAR gamma activation attenuates glucose intolerance induced by mTOR inhibition with rapamycin in rats. AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, v. 306, n. 9, p. E1046-E1054, MAY 2014. (09/15354-7)

PASCHOAL, VIVIAN A.; BELCHIOR, THIAGO; AMANO, MARIANE T.; BURGOS-SILVA, MARINA; PEIXOTO, ALBERT S.; MAGDALON, JULIANA; VIEIRA, THAYNA S.; ANDRADE, MAYNARA L.; MORENO, MAYARA F.; CHIMIN, PATRICIA; et al. Constitutive Activation of the Nutrient Sensor mTORC1 in Myeloid Cells Induced by Tsc1 Deletion Protects Mice from Diet-Induced Obesity. MOLECULAR NUTRITION & FOOD RESEARCH, v. 62, n. 17, SEP 2018. (15/19530-5, 12/02270-2, 11/10783-7, 09/15354-7)

MAGDALON, JULIANA; CHIMIN, PATRICIA; BELCHIOR, THIAGO; NEVES, RODRIGO X.; VIEIRA-LARA, MARCEL A.; ANDRADE, MAYNARA L.; FARIAS, TALITA S.; BOLSONI-LOPES, ANDRESSA; PASCHOAL, VIVIAN A.; YAMASHITA, ALEX S.; et al. Constitutive adipocyte mTORC1 activation enhances mitochondrial activity and reduces visceral adiposity in mice. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, v. 1861, n. 5, p. 430-438, MAY 2016. (10/51906-1, 11/03972-8, 12/25317-4, 15/19530-5, 13/14203-0, 09/15354-7)