Liver ACOX1 regulates levels of circulating lipids that promote metabolic health through adipose remodeling.

Autor: 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.; School of Life Sciences, Anhui Medical University, Hefei, 230032, China., Tan M; Division of Endocrinology, Metabolism & Lipid Research, Washington University School of Medicine, St. Louis, MO, 63110, USA., Mrad M; Division of Endocrinology, Metabolism & Lipid Research, Washington University School of Medicine, St. Louis, MO, 63110, USA., El Daibani A; Center for Clinical Pharmacology, Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, 63110, USA., Hu D; Division of Endocrinology, Metabolism & Lipid Research, 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; Center for Clinical Pharmacology, Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, 63110, USA., Hsu FF; Division of Endocrinology, Metabolism & Lipid Research, 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.; Department of Cell Biology and Physiology; 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. ilodhi@wustl.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 May 17; Vol. 15 (1), pp. 4214. Date of Electronic Publication: 2024 May 17.
DOI: 10.1038/s41467-024-48471-2
Abstrakt: The liver gene expression of the peroxisomal β-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 β-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 β-oxidation as an important regulator of metabolic homeostasis and suggests that manipulation of ACOX1 or its substrates may treat obesity-associated metabolic disorders.
(© 2024. The Author(s).)
Databáze: MEDLINE
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