The caracterization of antiinflammatory effect of palmitoleic acid suplemmentation in hepatic inflammation; The role of PPARs.

• Grant number: 16/01409-8
• Support Opportunities: Regular Research Grants
• Duration: June 01, 2016 - May 31, 2018
• Field of knowledge: Health Sciences - Nutrition - Nutrition Biochemistry
• Principal Investigator: José Cesar Rosa Neto
• Grantee: José Cesar Rosa Neto
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The obesity is na epidemic condition in developed and development countries. The high consumption of fat acids in ocidental diet, and the sedentarism induced the body weight gain, and the accumulation of fat acids in depots of adipose tissue, and other organs, such as liver. This condition caused the low grade inflammation, condition that it is presented in the genesis of co-morbidates associated with obesity. The excess of fat acids are depot in hepatic parenchyma, with increased in severity of liver damage. Recently, the palmitoleic acid demonstrated the positive effect in restored of glucose and insulin intolerance, and attenuation in liver inflammation in obese mice, and humans. These effects could be modulated by PPAR family, whereas the PPAR alfa increased the hepatic fat acids oxidation, and the PPAR gamma promoted the fat acids accumulation, but the two isoforms showed anti-inflammatory properties. The aim of our study is elucidate the molecular mechanisms of anti-inflammatory supplementation of palmitoleic acid in liver of obese mice. We utilized the C57BL/6J mice that will be divided into 4 groups: control group; control group + palmitoleic (oral gavage); high fat group; and high fat + palmitoleic. We will evaluate the insulin sensitivity, liver histology, and inflammation in liver, the types of macrophages infiltrated and the inflammation in hepatocytes and macrophages. In culture cells, of primary intraperitoneal macrophages and hepatocytes we will utilize inhibitor of PPAR alpha and gamma, with addiction of palmitoleic acid conjugated with BSA, in stimulated condition by LPS. We will analyze the cytokines production (in vivo and in vitro models), the molecular pathway (NFºB and JNK), the subsets of macrophage infiltration in liver by flow cytometry; and the expression of enzymes that regulated the lipids mediators (COX-1;COX-2:LOX5 and LOX12/15). (AU)

Scientific publications

(14)

(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)

MOSELE, FRANCIELLE C.; RICCI, RAFAEL BISSI; ABREU, PHABLO; ROSA NETO, JOSE C.. Muscle regeneration in adiponectin knockout mice showed early activation of anti-inflammatory response with perturbations in myogenesis. Journal of Cellular Physiology, v. 235, n. 9, JAN 2020. (16/01409-8)

SOUZA, CAMILA O.; TEIXEIRA, ALEXANDRE A. S.; BIONDO, LUANA AMORIM; SILVEIRA, LOREANA SANCHES; DE SOUZA BREDA, CRISTIANE N.; BRAGA, TARCIO T.; CAMARA, NIELS O. S.; BELCHIOR, THIAGO; FESTUCCIA, WILLIAM T.; DINIZ, TIEGO A.; et al. Palmitoleic acid reduces high fat diet-induced liver inflammation by promoting PPAR-gamma-independent M2a polarization of myeloid cells. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, v. 1865, n. 10, OCT 2020. (13/04765-1, 19/06172-4, 19/24112-9, 15/19530-5, 16/01409-8)

DE SOUZA, CAMILA OLIVEIRA; VALENZUELA, CARINA A.; BAKER, ELLA J.; MILES, ELIZABETH A.; NETO, JOSE C. ROSA; CALDER, PHILIP C.. Palmitoleic Acid has Stronger Anti-Inflammatory Potential in Human Endothelial Cells Compared to Oleic and Palmitic Acids. MOLECULAR NUTRITION & FOOD RESEARCH, v. 62, n. 20, OCT 2018. (13/04765-1, 15/06376-8, 16/01409-8)

DE SOUZA TEIXEIRA, ALEXANDRE ABILIO; LIRA, FABIO SANTOS; ROSA-NETO, JOSE CESAR. Aging with rhythmicity. Is it possible? Physical exercise as a pacemaker. Life Sciences, v. 261, NOV 15 2020. (15/16777-0, 16/01409-8, 19/09854-9, 18/24187-6)

DE SOUZA, CAMILA O.; TEIXEIRA, ALEXANDRE A. S.; BIONDO, LUANA A.; LIMA JUNIOR, EDSON A.; BATATINHA, HELENA A. P.; ROSA NETO, JOSE C.. Palmitoleic Acid Improves Metabolic Functions in Fatty Liver by PPAR-Dependent AMPK Activation. Journal of Cellular Physiology, v. 232, n. 8, p. 2168-2177, AUG 2017. (16/01409-8, 13/04765-1)

SILVEIRA, LOREANA SANCHES; BIONDO, LUANA AMORIM; DE SOUZA TEIXEIRA, ALEXANDRE ABILIO; DE LIMA JUNIOR, EDSON ALVES; CASTOLDI, ANGELA; SARAIVA CAMARA, NIELS OLSEN; FESTUCCIA, WILLIAN T.; ROSA-NETO, JOSE CESAR; LIRA, FABIO SANTOS. Macrophage immunophenotype but not anti-inflammatory profile is modulated by peroxisome proliferator-activated receptor gamma (PPAR gamma) in exercised obese mice. EXERCISE IMMUNOLOGY REVIEW, v. 26, p. 94-106, 2020. (18/21964-1, 13/25310-2, 14/01246-6, 16/01409-8)

TEIXEIRA, ALEXANDRE ABILIO S.; BIONDO, LUANA AMORIM; SILVEIRA, LOREANA S.; LIMA, EDSON A.; BATATINHA, HELENA A.; DINIZ, TIEGO A.; DE SOUZA, CAMILA OLIVEIRA; COMIN, JEFERSON; ROSA NETO, JOSE CESAR. Doxorubicin modulated clock genes and cytokines in macrophages extracted from tumor-bearing mice. CANCER BIOLOGY & THERAPY, JAN 2020. (15/16777-0, 19/09854-9, 16/01409-8)

BIONDO, LUANA AMORIM; TEIXEIRA, ALEXANDRE ABILIO S.; SILVEIRA, LOREANA S.; SOUZA, CAMILA O.; COSTA, RAQUEL G. F.; DINIZ, TIEGO A.; MOSELE, FRANCIELLE C.; ROSA NETO, JOSE CESAR. Tributyrin in Inflammation: Does White Adipose Tissue Affect Colorectal Cancer?. NUTRIENTS, v. 11, n. 1, JAN 2019. (16/01409-8, 16/06753-9)

PEREIRA BATATINHA, HELENA ANGELICA; DINIZ, TIEGO APARECIDO; DE SOUZA TEIXEIRA, ALEXANDRE ABILIO; KRUEGER, KARSTEN; ROSA-NETO, JOSE CESAR. Regulation of autophagy as a therapy for immunosenescence-driven cancer and neurodegenerative diseases: The role of exercise. Journal of Cellular Physiology, v. 234, n. 9, p. 14883-14895, SEP 2019. (16/10561-8, 16/01409-8)

DINIZ, TIEGO A.; JONCO AQUINO JUNIOR, JEFFERSON COMIN; MOSELE, FRANCIELLE CAROLINE; CABRAL-SANTOS, CAROLINA; DE LIMA JUNIOR, EDSON ALVES; DE SOUZA TEIXEIRA, ALEXANDRE ABILIO; LIRA, FABIO SANTOS; ROSA NETO, JOSE CESAR. Exercise-induced AMPK activation and IL-6 muscle production are disturbed in adiponectin knockout mice. CYTOKINE, v. 119, p. 71-80, JUL 2019. (16/02696-0, 16/01409-8)

DE SOUZA, CAMILA O.; VANNICE, GRETCHEN K.; ROSA NETO, JOSE C.; CALDER, PHILIP C.. Is Palmitoleic Acid a Plausible Nonpharmacological Strategy to Prevent or Control Chronic Metabolic and Inflammatory Disorders?. MOLECULAR NUTRITION & FOOD RESEARCH, v. 62, n. 1, JAN 2018. (16/01409-8, 13/04765-1)

SILVEIRA, LOREANA SANCHES; PEREIRA BATATINHA, HELENA ANGELICA; CASTOLDI, ANGELA; SARAIVA CAMARA, NIELS OLSEN; FESTUCCIA, WILLIAN T.; SOUZA, CAMILA OLIVEIRA; ROSA NETO, JOSE CESAR; LIRA, FABIO SANTOS. Exercise rescues the immune response fine-tuned impaired by peroxisome proliferator-activated receptors deletion in macrophages. Journal of Cellular Physiology, v. 234, n. 4, p. 5241-5251, APR 2019. (13/25310-2, 14/01246-6, 16/01409-8)

DE SOUZA TEIXEIRA, ALEXANDRE ABILIO; SOUZA, CAMILA O.; BIONDO, LUANA A.; SILVEIRA, LOREANA SANCHES; LIMA, EDSON A.; BATATINHA, HELENA A.; ARAUJO, ADRIANE PEREIRA; ALVES, MICHELE JOANA; HIRABARA, SANDRO MASSAO; CURI, RUI; et al. Short-term treatment with metformin reduces hepatic lipid accumulation but induces liver inflammation in obese mice. INFLAMMOPHARMACOLOGY, v. 26, n. 4, p. 1103-1115, AUG 2018. (13/09367-4, 15/16777-0, 16/01409-8)

SOUZA, CAMILA O.; TEIXEIRA, ALEXANDRE A. S.; BIONDO, LUANA A.; SILVEIRA, LOREANA S.; CALDER, PHILIP C.; ROSA NETO, JOSE C.. Palmitoleic acid reduces the inflammation in LPS-stimulated macrophages by inhibition of NF kappa B, independently of PPARs. Clinical and Experimental Pharmacology and Physiology, v. 44, n. 5, p. 566-575, MAY 2017. (16/01409-8, 13/04765-1)