TY - JOUR
T1 - Oleate-induced formation of fat cells with impaired insulin sensitivity
AU - Xie, Weisheng
AU - Hamilton, James A.
AU - Kirkland, James L.
AU - Corkey, Barbara E.
AU - Guo, Wen
N1 - Funding Information:
This work is supported by the National Institutes of Health grants RO1 DK059261 and HL67188.
PY - 2006/5
Y1 - 2006/5
N2 - Exogenous FA cause lipid accumulation in preadipocytes. We investigated whether the fat cells thus formed are metabolically distinct from adipocytes differentiated with standard methylisobutylxanthine, dexamethasone, and insulin (MDI) hormonal cocktail by comparing their expression of adipogenic genes, accumulation of TAG, lipogenesis, lipolysis, glucose uptake, and the effects of insulin on selected metabolic activities. Cells exposed to oleate began to accumulate TAG in parallel or prior to the induction of adipogenic genes, whereas cells treated with MDI expressed adipogenic genes before TAG accumulation. Oleate-treated fat cells also showed exaggerated basal lipolysis and weak response to insulin in both lipolysis regulation and glucose uptake. These findings were associated with increased basal phosphorylation of perilipin, increased Glut-1 but decreased Glut-4 expression, and reduced insulin-induced Akt phosphorylation. We suggest that this unique fat cell phenotype might be a mimetic of what can happen to fat cells formed in vivo under the influence of circulating FA and might be a useful model for in vitro studies of obesity-related insulin resistance in adipocytes.
AB - Exogenous FA cause lipid accumulation in preadipocytes. We investigated whether the fat cells thus formed are metabolically distinct from adipocytes differentiated with standard methylisobutylxanthine, dexamethasone, and insulin (MDI) hormonal cocktail by comparing their expression of adipogenic genes, accumulation of TAG, lipogenesis, lipolysis, glucose uptake, and the effects of insulin on selected metabolic activities. Cells exposed to oleate began to accumulate TAG in parallel or prior to the induction of adipogenic genes, whereas cells treated with MDI expressed adipogenic genes before TAG accumulation. Oleate-treated fat cells also showed exaggerated basal lipolysis and weak response to insulin in both lipolysis regulation and glucose uptake. These findings were associated with increased basal phosphorylation of perilipin, increased Glut-1 but decreased Glut-4 expression, and reduced insulin-induced Akt phosphorylation. We suggest that this unique fat cell phenotype might be a mimetic of what can happen to fat cells formed in vivo under the influence of circulating FA and might be a useful model for in vitro studies of obesity-related insulin resistance in adipocytes.
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U2 - 10.1007/s11745-006-5096-4
DO - 10.1007/s11745-006-5096-4
M3 - Article
C2 - 16711601
AN - SCOPUS:33646454453
SN - 0024-4201
VL - 41
SP - 267
EP - 271
JO - Lipids
JF - Lipids
IS - 3
ER -