Nutritional regulation of the fatty acid synthase (FAS) gene in human adipose tissue

We have recently repotted expression of lipoganic enzymes in human adipocytes. However, nutritional regulation of these enzymes has never been reported in human adipose tissue. To address mis issue, we used cultured human adipose tissue to investigate regulation of a key lipogenic enzyme, FAS by carbohydrates (glucose) and polyunsaturated fatty acids (linoleate). Human Adipose tissue was obtained from liposucticns, rinsed in Hanks Buffer then cultured in glucose-free DMEM for 24 hours. To investigate regulation of FAS by glucose, cultured adipose tissue was subsequently treated with 0, 5 or 25 mM glucose for 6 days. To investigate regulation of FAS by linoleate, cultures were treated with bov&ie serum albumin (control) or 200uM linoleic acid-albumin for 6 days in glucose supplemented media. Cells were then harvested and assayed for FAS enzyme activity which was normalized to DNA content. Glucose at 5mM did not significantly increase FAS activity compared to the control group of no glucose. However, glucose at 25mM induced a 2-fold increase in FAS activity (P< 0001) Treatment of cultures with 200uM of linoleic acid depressed FAS activity by 70% (P< 0001 ) These results demonstrate that FAS expression was induced by glucose and suppressed by linoleic acid in human adipose tissue. Further studies are necessary to determine mechanisms involved in regulation of human FAS gene by these nutrients.