Pharmacological agents targeting autophagy and their effects on lipolysis in human adipocytes

Qing Xu, Edwin Cm Mariman, Ellen E Blaak, Johan We Jocken*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Adipose tissue of metabolically compromised humans with obesity is often characterized by impaired regulation of autophagy pathway. However, data on the role of autophagy in human adipocyte lipid catabolism is scarce. Therefore, we investigated the effect of pharmacological agents (including 3-methyladenine (3MA), bafilomycin A1 (BAF), chloroquine (CQ) and lalistat-2 (L-stat), that target different stages of the autophagy pathway on lipid hydrolysis in differentiated human multipotent adipose-derived stem cells (hMADs). Glycerol and fatty acid release were measured as marker of lipid hydrolysis following starvation and β-adrenergic stimulation. Microtubule-associated protein light chain 3 ratio (LC3II/LC3I) and HSL phosphorylation (pHSL) were analyzed by Western blot. Our data indicate that pharmacological inhibition of the autophagy pathway reduced lipid hydrolysis in human adipocytes, although to a limited extent (10-15%). However, further research is needed to reveal the exact mechanism of action of these pharmacological agents and their interplay with cytosolic lipid breakdown in human adipocytes.

Original languageEnglish
Article number111555
Number of pages7
JournalMolecular and Cellular Endocrinology
Volume544
DOIs
Publication statusPublished - 15 Mar 2022

Keywords

  • ADIPOGENESIS
  • ADIPOSE-TISSUE
  • Autophagy
  • Autophagy pharmacological inhibitors
  • DEGRADATION
  • DELETION
  • FUSION
  • GUIDELINES
  • Human adipocyte
  • INHIBITION
  • LIPID DROPLET PROTEINS
  • Lipolysis
  • OBESITY
  • PERILIPIN FAMILY

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