Human adipocyte cholesterol. Concentration, localization, synthesis, and turnover

Abstract

By analysis of 124 specimens in 16 patients, isolated human adipocyte cholesterol concentration is highly correlated with fat cell size but not with plasma cholesterol concentration. Less than 6% of total cholesterol is esterified; after subcellular fractionation, 88% of the cholesterol is recovered in the triglyceride rich supernatant oil. This latter finding supports the observation that fat cell cholesterol is determined by triglyceride content, and hence by fat cell size. After intravenous administration of radioactive cholesterol, the sum of a three exponential equation was fitted simultaneously to both the plasma and adipocyte specific activity time curves in six patients. In five of the six, a slowly turning over pool (pool 3) closely fit the adipocyte data. Two model structures, mammillary and catenary, were fitted to the data. There was no synthesis in pool 3 using a mammillary model but a mean 5.3% of the total body production rate was found in compartment 3 if a catenary model was assumed. Although a catenary model is biologically unlikely, it could not be excluded. Obesity is associated with an increased cholesterol synthetic rate equal to 20 mg/day for each kg of body fat. To test (by an independent method) if this synthesis might be occurring in adipose tissue, human fat cells were obtained under a wide variety of dietary conditions and incubated in vitro with radioactive glucose or acetate. Incorporation of these precursors into sterol could account for no more than 1 mg cholesterol synthesis/kg fat per day. These in vitro data taken together with the in vivo mammillary compartmental analysis data are compatible with the possibility that the excess cholesterol synthesis of obesity occurs in pool 1, most likely from hepatic or intestinal sites.