Palmitoleic acid reduces high fat diet-induced liver inflammation by promoting PPAR-gamma-independent M2a polarization of myeloid cells

Author(s):Show less -

Souza, Camila O. ^[1] ; Teixeira, Alexandre A. S. ^[1] ; Biondo, Luana Amorim ^[1] ; Silveira, Loreana Sanches ^[1] ; de Souza Breda, Cristiane N. ^[2] ; Braga, Tarcio T. ^[2] ; Camara, Niels O. S. ^[2] ; Belchior, Thiago ^[3] ; Festuccia, William T. ^[3] ; Diniz, Tiego A. ^[1] ; Ferreira, Glaucio Monteiro ^[4] ; Hirata, Mario Hiroyuki ^[4] ; Chaves-Filho, Adriano B. ^[3] ; Yoshinaga, Marcos Y. ^[5] ; Miyamoto, Sayuri ^[5] ; Calder, Philip C. ^{[6, 7, 8, 9]} ; Sethi, Jaswinder K. ^{[6, 7, 8, 9]} ; Rosa Neto, Jose C. ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Cell & Dev Biol, Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Sao Paulo, SP - Brazil

^[3] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Sao Paulo, SP - Brazil

^[4] Univ Sao Paulo, Fac Pharmaceut Sci, Dept Pharm, Lab Mol Biol Appl Diag LBMAD, Sao Paulo, SP - Brazil

^[5] Univ Sao Paulo, Inst Chem, Dept Biochem, Sao Paulo, SP - Brazil

^[6] Univ Southampton, Fac Med, Human Dev & Hlth, Southampton, Hants - England

^[7] Univ Southampton, Natl Inst Hlth Res, Southampton Biomed Res Ctr, Southampton, Hants - England

^[8] Univ Hosp Southampton Natl Healthh Serv NHS Fdn T, Southampton, Hants - England

^[9] Univ Southampton, Inst Life Sci, Southampton, Hants - England

• Document type: Journal article
• Source: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS; v. 1865, n. 10 OCT 2020.
• Web of Science Citations: 0

Abstract

Palmitoleic acid (POA, 16:1n-7) is a lipokine that has potential nutraceutical use to treat non-alcoholic fatty liver disease. We tested the effects of POA supplementation (daily oral gavage, 300 mg/Kg, 15 days) on murine liver inflammation induced by a high fat diet (HFD, 59% fat, 12 weeks). In HFD-fed mice, POA supplementation reduced serum insulin and improved insulin tolerance compared with oleic acid (OA, 300 mg/Kg). The livers of POA-treated mice exhibited less steatosis and inflammation than those of OA-treated mice with lower inflammatory cytokine levels and reduced toll-like receptor 4 protein content. The anti-inflammatory effects of POA in the liver were accompanied by a reduction in liver macrophages (LM, CD11c(+); F4/80(+); CD86(+)), an effect that could be triggered by peroxisome proliferator activated receptor (PPAR)-gamma, a lipogenic transcription factor upregulated in livers of POA-treated mice. We also used HFD-fed mice with selective deletion of PPAR-gamma in myeloid cells (PPAR-gamma KOLyzCre+) to test whether the beneficial anti-inflammatory effects of POA are dependent on macrophages PPAR-gamma. POA-mediated improvement of insulin tolerance was tightly dependent on myeloid PPAR-gamma, while POA anti-inflammatory actions including the reduction in liver inflammatory cytokines were preserved in mice bearing myeloid cells deficient in PPAR-gamma. This overlapped with increased CD206(+) (M2a) cells and downregulation of CD86(+) and CD11c(+) liver macrophages. Moreover, POA supplementation increased hepatic AMPK activity and decreased expression of the fatty acid binding scavenger receptor, CD36. We conclude that POA controls liver inflammation triggered by fat accumulation through induction of M2a macrophages independently of myeloid cell PPAR-gamma. (AU)

• FAPESP's process: 13/04765-1 - Palmitoleic acid supplementation effects on immune-metabolics alterations induced by high fat diet on PPAR knockout mice
• Grantee: Camila Oliveira de Souza
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 19/06172-4 - Post-doctorate fellow in search of new drugs against Hypercholesterolemia, based on specific genetic and epigenetic markers of the Brazilian population
• Grantee: Glaucio Monteiro Ferreira
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 19/24112-9 - Novel HMG-CoA reductase inhibitors development by integrating dyslipidemic patients' genetic studies and molecular modelling
• Grantee: Glaucio Monteiro Ferreira
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• FAPESP's process: 15/19530-5 - Involvement of the nutrient sensor mTOR in the development of obesity associated chronic metabolic diseases
• Grantee: William Tadeu Lara Festuccia
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 16/01409-8 - The caracterization of antiinflammatory effect of palmitoleic acid suplemmentation in hepatic inflammation; The role of PPARs.
• Grantee: José Cesar Rosa Neto
• Support Opportunities: Regular Research Grants