Synthesis of fatty acids and cholesterol by liver, adipose tissue and intestinal mucosa from obese and control patients.

Abstract

Biopsies of adipose tissue, liver and small bowel mucosa obtained from grossly obese and control subjects were used to study absolute rates of fatty acid, cholesterol, and other nonsaponifiable lipid synthesis using glucose as substrate and 3H2O as the isotopic marker. Fatty acid synthesis in subcutaneous adipose tissue expressed on a cell basis was greater in obese than control subjects and was stimulated by a high concentration of insulin (1000 micro U/ml), but not by a lower amount (100 micro U/ml). Fatty acid synthesis in omental adipose tissue exceeded by 3-fold that of subcutaneous fat. Fatty acid synthesis in obese liver was twice that of control liver and 20 times greater than obese adipose tissue. In terms of total organ activity fatty acid synthesis in fat tissue equalled or exceeded that of liver in both obese and control subjects. The cholesterol content of obese adipose tissue 1.86 +/- 0.11 mg/g exceeded that of controls 1.47 +/- 0.07 mg/g. All tissues examined synthesized cholesterol and nonsaponifiable lipids, liver greater than adipose tissue greater than small bowel mucosa. Nonsaponifiable lipid synthesis per gram of adipose tissue or liver was similar in obese and control tissue. The synthesis of total nonsaponifiable lipids including sterols, hydrocarbons and squalene was appreciable in adipose tissue and was approximately 15% of that of liver. However, cholesterol synthesis in the liver exporessed in terms of total organ activity was 50 times that in adipose tissue. The study demonstrates by direct comparison that liver is the dominant cholesterogenic organ in man and also shows that adipose tissue is a significant site of formation of fatty acids and nonsaponifiable lipids.