PPAR gamma is a major regulator of branched-chain amino acid blood levels and catabolism in white and brown adipose tissues

Autor(es):Mostrar menos -

Blanchard, Pierre-Gilles ^[1] ; Moreira, Rafael J. ^[2] ; Castro, Erique ^[2] ; Caron, Alexandre ^[1] ; Cote, Marie ^[1] ; Andrade, Maynara L. ^[2] ; Oliveira, Tiago E. ^[2] ; Ortiz-Silva, Milene ^[2] ; Peixoto, Albert S. ^[2] ; Dias, France Anne ^[3] ; Gelinas, Yves ^[1] ; Guerra-Sa, Renata ^[3] ; Deshaies, Yves ^[1] ; Festuccia, William T. ^[2]

Afiliação do(s) autor(es)

^[1] Laval Univ, Quebec Heart & Lung Inst, Fac Med, Dept Med, Quebec City, PQ - Canada

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Ave Prof Lineu Prestes 1524, BR-05508000 Sao Paulo - Brazil

^[3] Univ Fed Ouro Preto, Dept Biol Sci, ICEB, Ouro Preto - Brazil

• Tipo de documento: Artigo Científico
• Fonte: METABOLISM-CLINICAL AND EXPERIMENTAL; v. 89, p. 27-38, DEC 2018.
• Citações Web of Science: 5

Resumo

Objective: We investigated whether PPAR gamma modulates adipose tissue BCAA metabolism, and whether this mediates the attenuation of obesity-associated insulin resistance induced by pharmacological PPAR gamma activation. Methods: Mice with adipocyte deletion of one or two PPAR gamma copies fed a chow diet and rats fed either chow, or high fat (HF) or HF supplemented with BCAA (HF/BCAA) diets treated with rosiglitazone (30 or 15 mg/kg/day, 14 days) were evaluated for glucose and BCAA homeostasis. Results: Adipocyte deletion of one PPAR gamma copy increased mice serum BCAA and reduced inguinal white (iWAT) and brown (BAT) adipose tissue BCAA incorporation into triacylglycerol, as well as mRNA levels of branched chain aminotransferase (BCAT)2 and branched-chain alpha-Retoacid dehydrogenase (BCKDH) complex subunits. Adipocyte deletion of two PPAR gamma copies induced lipodystrophy, severe glucose intolerance and markedly increased serum BCAA. Rosiglitazone abolished the increase in serum BCAA induced by adipocyte PPAR gamma deletion. In rats, HF increased serum BCAA, such levels being further increased by BCAA supplementation. Rosiglitazone, independently of diet, lowered serum BCAA and upregulated iWAT and BAT BCAT and BCKDH activities. This was associated with a reduction in mTORC1-dependent inhibitory serine phosphorylation of IRS1 in skeletal muscle and whole-body insulin resistance evaluated by HOMA-IR. Conclusions: PPAR gamma, through the regulation of both BAT and iWAT BCAA catabolism in lipoeutrophic mice and muscle insulin responsiveness and proteolysis in lipodystrophic mice, is a major determinant of circulating BCAA levels. PPAR gamma agonism, therefore, may improve whole-body and muscle insulin sensitivity by reducing blood BCAA, alleviating mTORC1-mediated inhibitory IRS1 phosphorylation. (C) 2018 Elsevier Inc. All rights reserved. (AU)

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• Modalidade de apoio: Auxílio à Pesquisa - Regular