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

adipose depots Adult Male 0301 basic medicine 0303 health sciences perilipins thiazolidinedione QD415-436 Lipid Droplets Middle Aged Biochemistry protein carbonylation Rosiglitazone 03 medical and health sciences Phenotype Adipose Tissue Adipocytes Humans Hypoglycemic Agents Female Oxidation-Reduction fatty acid oxidation Aged
DOI: 10.1194/jlr.m091173 Publication Date: 2019-02-20T01:07:01Z
ABSTRACT
Treatment with PPARγ 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 (PGC1α, 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.
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