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SHR Neuro Cancer Cardio Lipid Metab Microb

Xia, W; Pessentheiner, AR; Hofer, DC; Amor, M; Schreiber, R; Schoiswohl, G; Eichmann, TO; Walenta, E; Itariu, B; Prager, G; Hackl, H; Stulnig, T; Kratky, D; Rülicke, T; Bogner-Strauss, JG.
Loss of ABHD15 Impairs the Anti-lipolytic Action of Insulin by Altering PDE3B Stability and Contributes to Insulin Resistance.
Cell Rep. 2018; 23(7):1948-1961 Doi: 10.1016/j.celrep.2018.04.055 [OPEN ACCESS]
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Leading authors Med Uni Graz: Pessentheiner Ariane Raphaela
Co-authors Med Uni Graz: Amor Melina; Kratky Dagmar; Schoiswohl Gabriele Maria; Schreiber Renate
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Abstract:: Elevated circulating fatty acids (FAs) contribute to obesity-associated metabolic complications, but the mechanisms by which insulin suppresses lipolysis are poorly understood. We show that α/β-hydrolase domain-containing 15 (ABHD15) is required for the anti-lipolytic action of insulin in white adipose tissue (WAT). Neither insulin nor glucose treatments can suppress FA mobilization in global and conditional Abhd15-knockout (KO) mice. Accordingly, insulin signaling is impaired in Abhd15-KO adipocytes, as indicated by reduced AKT phosphorylation, glucose uptake, and de novo lipogenesis. In vitro data reveal that ABHD15 associates with and stabilizes phosphodiesterase 3B (PDE3B). Accordingly, PDE3B expression is decreased in the WAT of Abhd15-KO mice, mechanistically explaining increased protein kinase A (PKA) activity, hormone-sensitive lipase (HSL) phosphorylation, and undiminished FA release upon insulin signaling. Ultimately, Abhd15-KO mice develop insulin resistance. Notably, ABHD15 expression is decreased in humans with obesity and diabetes compared to humans with obesity and normal glucose tolerance, identifying ABHD15 as a potential therapeutic target to mitigate insulin resistance. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
Find related publications in this database (using NLM MeSH Indexing): 3T3-L1 Cells -; Adipose Tissue, White - metabolism; Animals -; Carboxylic Ester Hydrolases - genetics; Carboxylic Ester Hydrolases - metabolism; Cyclic Nucleotide Phosphodiesterases, Type 3 - metabolism; Diet, High-Fat -; Enzyme Stability - drug effects; Fatty Acids - metabolism; Female -; Gene Expression Regulation - drug effects; Glucose - metabolism; Humans -; Insulin - pharmacology; Insulin Resistance -; Lipolysis - drug effects; Male -; Membrane Proteins - deficiency; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice -; Mice, Inbred C57BL -; Mice, Knockout -; Obesity - genetics; Obesity - pathology; Phenotype -