ABHD4 regulates adipocyte differentiation in vitro but does not affect adipose tissue lipid metabolism in mice.

Autor:	Seramur ME; Department of Internal Medicine, Section on Molecular Medicine, Wake Forest University School of Medicine, Winston Salem, NC, USA., Sink S; Department of Internal Medicine, Section on Molecular Medicine, Wake Forest University School of Medicine, Winston Salem, NC, USA., Cox AO; Wake Forest Baptist Comprehensive Cancer Center Proteomics and Metabolomics Shared Resource, Wake Forest University School of Medicine, Winston Salem, NC, USA., Furdui CM; Department of Internal Medicine, Section on Molecular Medicine, Wake Forest University School of Medicine, Winston Salem, NC, USA., Key CC; Department of Internal Medicine, Section on Molecular Medicine, Wake Forest University School of Medicine, Winston Salem, NC, USA. Electronic address: cchuang@wakehealth.edu.
Jazyk:	angličtina
Zdroj:	Journal of lipid research [J Lipid Res] 2023 Aug; Vol. 64 (8), pp. 100405. Date of Electronic Publication: 2023 Jun 22.
DOI:	10.1016/j.jlr.2023.100405
Abstrakt:	Alpha/beta hydrolase domain-containing protein 4 (ABHD4) catalyzes the deacylation of N-acyl phosphatidyl-ethanolamine (NAPE) and lyso-NAPE to produce glycerophospho-N-acyl ethanolamine (GP-NAE). Through a variety of metabolic enzymes, NAPE, lyso-NAPE, and GP-NAE are ultimately converted into NAE, a group of bioactive lipids that control many physiological processes including inflammation, cognition, food intake, and lipolysis (i.e., oleoylethanolamide or OEA). In a diet-induced obese mouse model, adipose tissue Abhd4 gene expression positively correlated with adiposity. However, it is unknown whether Abhd4 is a causal or a reactive gene to obesity. To fill this knowledge gap, we generated an Abhd4 knockout (KO) 3T3-L1 pre-adipocyte. During adipogenic stimulation, Abhd4 KO pre-adipocytes had increased adipogenesis and lipid accumulation, suggesting Abhd4 is responding to (a reactive gene), not contributing to (not a causal gene), adiposity, and may serve as a mechanism for protecting against obesity. However, we did not observe any differences in adiposity and metabolic outcomes between whole-body Abhd4 KO or adipocyte-specific Abhd4 KO mice and their littermate control mice (both male and female) on chow or a high-fat diet. This might be because we found that deletion of Abhd4 did not affect NAE such as OEA production, even though Abhd4 was highly expressed in adipose tissue and correlated with fasting adipose OEA levels and lipolysis. These data suggest that ABHD4 regulates adipocyte differentiation in vitro but does not affect adipose tissue lipid metabolism in mice despite nutrient overload, possibly due to compensation from other NAPE and NAE metabolic enzymes. Competing Interests: Conflict of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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