Studies on mechanisms of mitochondrial uncoupling by non-esterified fatty acids as a strategy for prevention / treatment of obesity

• Grant number: 10/17259-9
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: February 01, 2012
• End date: July 31, 2016
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Luciane Carla Alberici
• Grantee: Luciane Carla Alberici
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated researchers: Carlos Curti ; Norberto Peporine Lopes
• Associated scholarship(s): 15/04028-2 - Study of mitochondrial energy dissipation systems in mice supplemented with conjugated linoleic acid in association with fish oil, BP.IC; 14/02654-0 - Study of mitochondrial energy dissipation induced by diet suplementation with linoleic conjugated acid (CLA) associated to oleic acid, BP.IC

Abstract

The increased prevalence of obesity in worldwide is a result of Western lifestyle, characterized by high caloric intake associated with physical inactivity. Obesity increases the risk to various diseases including diabetes, heart disease, hypertension and stroke, accounting for one in every three deaths in worldwide. These diseases represent a major public health problem and indicate the need to develop new and effective treatment strategies. Mitochondria are responsible for cellular respiration and ATP synthesis in eukaryotes and are the main sources of reactive oxygen species (ROS). These organelles have their own systems of energy dissipation induced by increased intracellular concentrations of nonesterified fatty acids (also appointed as FFA) such as uncoupling proteins and ATP sensitive K+ channels. These mechanisms promote a slight decrease in the electrochemical potential of H+, which is replenished at the expense of increased respiration and oxidation of energy substrates, increasing the energetic body expenditure. It is known that the decrease of electrochemical potential of H+ can reduce mitochondrial ROS generation. The purpose of this project is induce these mechanisms of energy dissipation by increasing the intracellular concentration of FFA as a strategy for obesity treatment. Accordingly, two distinct lines of induction will be employed: I - reduction in the esterification rate of FFA through reducing the activity of acyl-CoA synthetase by triacsin C, which can increase the half-life of these molecules in the cytosol; II - increase the supply of FFA to the liver and skeletal muscle by dietary supplementation with conjugated linoleic acid alone or combined with other AGL. (AU)

Scientific publications

(16)

(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)

DA COSTA, RAFAEL MENEZES; FAIS, RAFAEL S.; DECHANDT, CARLOS R. P.; LOUZADA-JUNIOR, PAULO; ALBERICI, LUCIANE C.; LOBATO, NUBIA S.; TOSTES, RITA C.. Increased mitochondrial ROS generation mediates the loss of the anti-contractile effects of perivascular adipose tissue in high-fat diet obese mice. British Journal of Pharmacology, v. 174, n. 20, SI, p. 3527-3541, OCT 2017. (13/08216-2, 10/17259-9)

SOUZA, ANDERSON DE OLIVEIRA; COUTO-LIMA, CARLOS ANTONIO; ROSA MACHADO, MAIARO CABRAL; ESPREAFICO, ENILZA MARIA; PINHEIRO RAMOS, RICARDO GUELERMAN; ALBERICI, LUCIANE CARLA. Protective action of Omega-3 on paraquat intoxication in Drosophila melanogaster. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES, v. 80, n. 19-21, SI, p. 1050-1063, 2017. (10/17259-9)

ROSSIGNOLI, CAMILA P.; DECHANDT, CARLOS R. P.; SOUZA, ANDERSON O.; SAMPAIO, IGOR H.; VICENTINI, TATIANE M.; TEODORO, BRUNO G.; CAVALCANTI NETO, MARINALDO PACIFICO; FERRARI, GUSTAVO DUARTE; COUTO-LIMA, CARLOS A.; ALBERICI, LUCIANE C.. Effects of intermittent dietary supplementation with conjugated linoleic acid and fish oil (EPA/DHA) on body metabolism and mitochondrial energetics in mice. JOURNAL OF NUTRITIONAL BIOCHEMISTRY, v. 60, p. 16-23, OCT 2018. (10/17259-9)

REIS, FELIPPE H. Z.; PARDO-ANDREU, GILBERTO L.; NUNEZ-FIGUEREDO, YANIER; CUESTA-RUBIO, OSMANY; MARIN-PRIDA, JAVIER; UYEMURA, SERGIO A.; CURTI, CARLOS; ALBERICI, LUCIANE C.. Clusianone, a naturally occurring nemorosone regioisomer, uncouples rat liver mitochondria and induces HepG2 cell death. Chemico-Biological Interactions, v. 212, p. 20-29, APR 5 2014. (10/17259-9)

DA SILVA, BRENDA DE OLIVEIRA; ALBERICI, LUCIANE CARLA; RAMOS, LETICIA FERREIRA; SILVA, CAIO MATEUS; DA SILVEIRA, MARINA BONFOGO; DECHANT, CARLOS R. P.; FRIEDMAN, SCOTT L.; SAKANE, KUMIKO KOIBUCHI; GONCALVES, LETICIA ROCHA; MORAES, KAREN C. M.. Altered global microRNA expression in hepatic stellate cells LX-2 by angiotensin-(1-7) and miRNA-1914-5p identification as regulator of pro-fibrogenic elements and lipid metabolism. INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, v. 98, p. 137-155, MAY 2018. (09/07671-2, 13/21186-5, 10/17259-9)

DA COSTA, RAFAEL MENEZES; FAIS, RAFAEL S.; DECHANDT, CARLOS R. P.; LOUZADA-JUNIOR, PAULO; ALBERICI, LUCIANE C.; LOBATO, NUBIA S.; TOSTES, RITA C.. Increased mitochondrial ROS generation mediates the loss of the anti-contractile effects of perivascular adipose tissue in high-fat diet obese mice. British Journal of Pharmacology, v. 174, n. 20, p. 15-pg., 2017-10-01. (13/08216-2, 10/17259-9)

SOUZA, ANDERSON DE OLIVEIRA; COUTO-LIMA, CARLOS ANTONIO; ROSA MACHADO, MAIARO CABRAL; ESPREAFICO, ENILZA MARIA; PINHEIRO RAMOS, RICARDO GUELERMAN; ALBERICI, LUCIANE CARLA. Protective action of Omega-3 on paraquat intoxication in Drosophila melanogaster. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES, v. 80, n. 19-21, p. 14-pg., 2017-01-01. (10/17259-9)

TEODORO, BRUNO G.; SAMPAIO, IGOR H.; BOMFIM, LUCAS H. M.; QUEIROZ, ANDRE L.; SILVEIRA, LEONARDO R.; SOUZA, ANDERSON O.; FERNANDES, ANNA M. A. P.; EBERLIN, MARCOS N.; HUANG, TAI-YU; ZHENG, DONGHAI; et al. Long-chain acyl-CoA synthetase 6 regulates lipid synthesis and mitochondrial oxidative capacity in human and rat skeletal muscle. JOURNAL OF PHYSIOLOGY-LONDON, v. 595, n. 3, p. 677-693, FEB 2017. (10/17259-9)

DA SILVA, MARCIA F.; NATALI, ANTONIO J.; DA SILVA, EDSON; GOMES, GILTON J.; TEODORO, BRUNO G.; CUNHA, DAISE N. Q.; DRUMMOND, LUCAS R.; DRUMMOND, FILIPE R.; MOURA, ANSELMO G.; BELFORT, FELIPE G.; et al. Attenuation of Ca2+ homeostasis, oxidative stress, and mitochondrial dysfunctions in diabetic rat heart: insulin therapy or aerobic exercise?. Journal of Applied Physiology, v. 119, n. 2, p. 148-156, JUL 15 2015. (10/17259-9)

SANTOS, DOUGLAS ELIAS; ALBERICI, LUCIANE CARLA; HARTFELDER, KLAUS. Mitochondrial structure and dynamics as critical factors in honey bee (Apis mellifera L.) caste development. Insect Biochemistry and Molecular Biology, v. 73, p. 1-11, JUN 2016. (13/24733-7, 10/17259-9)

DECHANDT, CARLOS R. P.; COUTO-LIMA, CARLOS A.; ALBERICI, LUCIANE C.. Triglyceride depletion of brown adipose tissue enables analysis of mitochondrial respiratory function in permeabilized biopsies. Analytical Biochemistry, v. 515, p. 55-60, DEC 15 2016. (10/17259-9)

PARDO ANDREU, GILBERTO L.; REIS, FELIPPE H. Z.; DALALIO, FELIPE M.; NUNEZ FIGUEREDO, YANIER; CUESTA RUBIO, OSMANY; UYEMURA, SERGIO A.; CURTI, CARLOS; ALBERICI, LUCIANE C.. The cytotoxic effects of brown Cuban propolis depend on the nemorosone content and may be mediated by mitochondrial uncoupling. Chemico-Biological Interactions, v. 228, p. 28-34, FEB 25 2015. (10/17259-9)

ROCHA CATALAO, CARLOS HENRIQUE; SANTOS-JUNIOR, NILTON NASCIMENTO; ANGENENDT DA COSTA, LUIS HENRIQUE; SOUZA, ANDERSON OLIVEIRA; ALBERICI, LUCIANE CARLA; ALVES ROCHA, MARIA JOSE. Brain Oxidative Stress During Experimental Sepsis Is Attenuated by Simvastatin Administration. Molecular Neurobiology, v. 54, n. 9, p. 7008-7018, NOV 2017. (10/17259-9)

DECHANDT, CARLOS R. P.; ZUCCOLOTTO-DOS-REIS, FELIPPE H.; TEODORO, BRUNO G.; FERNANDES, ANNA MARIA A. P.; EBERLIN, MARCOS N.; KETTELHUT, ISIS C.; CURTI, CARLOS; ALBERICI, LUCIANE C.. Triacsin C reduces lipid droplet formation and induces mitochondrial biogenesis in primary rat hepatocytes. Journal of Bioenergetics and Biomembranes, v. 49, n. 5, p. 399-411, OCT 2017. (10/17259-9)

BARALDI, FLAVIA G.; VICENTINI, TATIANE M.; TEODORO, BRUNO G.; DALALIO, FELIPE M.; DECHANDT, CARLOS R. P.; PRADO, IEDA M. R.; CURTI, CARLOS; CARDOSO, FERNANDA C.; UYEMURA, SERGIO A.; ALBERICI, LUCIANE C.. The combination of conjugated linoleic acid (CLA) and extra virgin olive oil increases mitochondrial and body metabolism and prevents CLA-associated insulin resistance and liver hypertrophy in C57B1/6 mice. JOURNAL OF NUTRITIONAL BIOCHEMISTRY, v. 28, p. 147-154, FEB 2016. (10/17259-9)

PEREIRA, AMANDA F.; SA, LARISSA L.; REIS, FELIPPE H. Z.; CARDOSO, FERNANDA C.; ALBERICI, ROSANA M.; PRADO, IEDA M. R.; EBERLIN, MARCOS N.; UYEMURA, SERGIO A.; CURTI, CARLOS; ALBERICI, LUCIANE C.. Administration of a murine diet supplemented with conjugated linoleic acid increases the expression and activity of hepatic uncoupling proteins. Journal of Bioenergetics and Biomembranes, v. 44, n. 5, p. 587-596, OCT 2012. (10/17259-9)