Rosiglitazone remodels the lipid droplet and britens human visceral and subcutaneous adipocytes ex vivo

Mi Jeong Lee, Sukanta Jash, Jessica E.C. Jones, Vishwajeet Puri, Susan K. Fried

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Treatment with PPAR agonists in vivo improves human adipocyte metabolism, but the cellular mechanisms and possible depot differences in responsiveness to their effects are poorly understood. To examine the ex vivo metabolic effects of rosiglitazone (Rosi), we cultured explants of human visceral (omental) and abdominal subcutaneous adipose tissues for 7 days. Rosi increased mRNA levels of transcriptional regulators of brite/beige adipocytes (PGC1, PRDM16), triglyceride synthesis (GPAT3, DGAT1), and lipolysis (ATGL) similarly in adipose tissues from both depots. In parallel, Rosi increased key modulators of FA oxidation (UCP1, FABP3, PLIN5 protein), rates of FA oxidation, and protein levels of electron transport complexes, suggesting an enhanced respiratory capacity as confirmed in newly differentiated adipocytes. Rosi led to the formation of small lipid droplets (SLDs) around the adipocyte central lipid droplet; each SLD was decorated with redistributed mitochondria that colocalized with PLIN5. SLD maintenance required lipolysis and FA reesterification. Rosi thus coordinated a structural and metabolic remodeling in adipocytes from both visceral and subcutaneous depots that enhanced oxidative capacity. Selective targeting of these cellular mechanisms to improve adipocyte FA handling may provide a new approach to treat metabolic complications of obesity and diabetes.

Original languageEnglish
Pages (from-to)856-868
Number of pages13
JournalJournal of Lipid Research
Volume60
Issue number4
DOIs
StatePublished - 2019

Keywords

  • Adipose depots
  • Fatty acid oxidation
  • Perilipins
  • Protein carbonylation
  • Thiazolidinedione

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