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
AUTHORS (5)
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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