ASC-1 transporter-dependent amino acid uptake is required for the efficient thermogenic response of human adipocytes to adrenergic stimulation.

Abstract

Brown and beige adipocytes dissipate energy by uncoupling protein 1 (UCP1)-dependent and UCP1-independent thermogenesis, which may be utilized to develop treatments against obesity. We have found that mRNA and protein expression of the alanine/serine/cysteine transporter-1 (ASC-1) was induced during adipocyte differentiation of human brown-prone deep neck and beige-competent subcutaneous neck progenitors, and SGBS preadipocytes. cAMP stimulation of differentiated adipocytes led to elevated uptake of serine, cysteine, and glycine, in parallel with increased oxygen consumption, augmented UCP1-dependent proton leak, increased creatine-driven substrate cycle-coupled respiration, and upregulation of thermogenesis marker genes and several respiratory complex subunits; these outcomes were impeded in the presence of the specific ASC-1 inhibitor, BMS-466442. Our data suggest that ASC-1-dependent consumption of serine, cysteine, and glycine is required for efficient thermogenic stimulation of human adipocytes.

• Authors: Rini Arianti, Boglárka Ágnes Vinnai, Beáta B Tóth, Abhirup Shaw, Éva Csősz, Attila Vámos, Ferenc Győry, Pamela Fischer-Posovszky, Martin Wabitsch, Endre Kristóf, László Fésüs
• Journal: FEBS letters (FEBS Lett) Vol. 595 Issue 16 Pg. 2085-2098 (08 2021) ISSN: 1873-3468 [Electronic] England
• PMID: 34197627 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

Chemical References

• Adrenergic Agents
• Amino Acid Transport System y+
• Amino Acids
• SLC7A10 protein, human

Topics

• Adipocytes (drug effects, metabolism)
• Adrenergic Agents (pharmacology)
• Amino Acid Transport System y+ (metabolism)
• Amino Acids (metabolism)
• Biological Transport (drug effects)
• Humans
• Thermogenesis (drug effects)