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Liver ACOX1 regulates levels of circulating lipids that promote metabolic health through adipose remodeling.
Lu, Dongliang; He, Anyuan; Tan, Min; Mrad, Marguerite; El Daibani, Amal; Hu, Donghua; Liu, Xuejing; Kleiboeker, Brian; Che, Tao; Hsu, Fong-Fu; Bambouskova, Monika; Semenkovich, Clay F; Lodhi, Irfan J.
Afiliação
  • Lu D; Division of Endocrinology, Metabolism & Lipid Research, Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • He A; Division of Endocrinology, Metabolism & Lipid Research, Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Tan M; School of Life Sciences, Anhui Medical University, Hefei, 230032, China.
  • Mrad M; Division of Endocrinology, Metabolism & Lipid Research, Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • El Daibani A; Division of Endocrinology, Metabolism & Lipid Research, Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Hu D; Center for Clinical Pharmacology, Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Liu X; Division of Endocrinology, Metabolism & Lipid Research, Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Kleiboeker B; Division of Endocrinology, Metabolism & Lipid Research, Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Che T; Division of Endocrinology, Metabolism & Lipid Research, Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Hsu FF; Center for Clinical Pharmacology, Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Bambouskova M; Division of Endocrinology, Metabolism & Lipid Research, Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Semenkovich CF; Division of Endocrinology, Metabolism & Lipid Research, Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Lodhi IJ; Division of Endocrinology, Metabolism & Lipid Research, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Nat Commun ; 15(1): 4214, 2024 May 17.
Article em En | MEDLINE | ID: mdl-38760332
ABSTRACT
The liver gene expression of the peroxisomal ß-oxidation enzyme acyl-coenzyme A oxidase 1 (ACOX1), which catabolizes very long chain fatty acids (VLCFA), increases in the context of obesity, but how this pathway impacts systemic energy metabolism remains unknown. Here, we show that hepatic ACOX1-mediated ß-oxidation regulates inter-organ communication involved in metabolic homeostasis. Liver-specific knockout of Acox1 (Acox1-LKO) protects mice from diet-induced obesity, adipose tissue inflammation, and systemic insulin resistance. Serum from Acox1-LKO mice promotes browning in cultured white adipocytes. Global serum lipidomics show increased circulating levels of several species of ω-3 VLCFAs (C24-C28) with previously uncharacterized physiological role that promote browning, mitochondrial biogenesis and Glut4 translocation through activation of the lipid sensor GPR120 in adipocytes. This work identifies hepatic peroxisomal ß-oxidation as an important regulator of metabolic homeostasis and suggests that manipulation of ACOX1 or its substrates may treat obesity-associated metabolic disorders.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Acil-CoA Oxidase / Metabolismo dos Lipídeos / Fígado / Obesidade Limite: Animals Idioma: En Revista: Nat Commun Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Acil-CoA Oxidase / Metabolismo dos Lipídeos / Fígado / Obesidade Limite: Animals Idioma: En Revista: Nat Commun Ano de publicação: 2024 Tipo de documento: Article