Lipolytic Products Activate Peroxisome Proliferator-activated Receptor (PPAR) and in Brown Adipocytes to Match Fatty Acid Oxidation with Supply (original) (raw)
2012, Journal of Biological Chemistry
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PPAR-γ response element activity in intact primary human adipocytes: effects of fatty acids
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Objective: We studied the activity and regulation of the peroxisome proliferator-activated receptor-␥ response element (PPRE) in primary human adipocytes. Methods: We transfected primary human adipocytes with a plasmid-encoding firefly luciferase cDNA under control of a PPRE from the acyl-coenzyme A oxidase gene by using our newly developed electroporation-based method. Several fatty acids were added to the fat cells to study potential activation of peroxisome proliferator-activated receptor-␥. Results: Cells responded maximally to 5 M of rosiglitazone at a 5.1 Ϯ 1.4-fold over basal increase in luciferase activity. There was a positive correlation between body mass index and the response to 5 M of rosiglitazone (r ϭ 0.36, P ϭ 0.03). Patients with type 2 diabetes had similar basal PPRE activity but responded more strongly to 5 M of rosiglitazone than did non-diabetic subjects (10.2 Ϯ 5-fold and 5.4 Ϯ 1-fold over basal increase, respectively, P Ͻ 0.0001). Among saturated fatty acids, lauric acid was without effect, but 10 M of palmitic or stearic acid increased PPRE activity 20% to 35% above basal levels. Monounsaturated palmitoleic acid at 1 M induced a PPRE transcriptional activity that corresponded to half the therapeutic levels of rosiglitazone. Conclusion: Adipocytes from obese subjects and patients with type 2 diabetes responded particularly strongly to the effect of rosiglitazone on PPRE. Because fatty acids in the diet can affect the transcriptional activity of peroxisome proliferator-activated receptor-␥ over decades, the stimulation induced by stearic and palmitoleic acids can affect insulin sensitivity and, hence, cardiovascular morbidity and mortality in humans.
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