A B S T R A C T By analysis of 124 specimens in 16 different 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 fit 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 kilogram 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 togethed with the in vivo mammillary compartmental analysis data are compatible with the possibility that Portions of this work were presented at

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Adipocyte triglyceride, cholesterol, and tocopherol contents were examined in three human obese subjects, all over 150% of ideal weight, who were placed on weight reduction formula diets for 11, 21, and 25 wk, respectively. Body weight decreased from 77 to 63 kg, 188 to 147 kg, and 147 to 99 kg, respectively. All subjects had normal serum cholesterol and triglyceride levels, and these did not vary greatly during weight reduction. Subcutaneous fat was obtained at frequent intervals by needle aspiration from the buttocks before and during weight reduction. Adipocyte size was measured by osmium tetroxide fixation technique, tissue cholesterol content by GLC, tissue triglyceride content by lipid extraction, and tissue tocopherol by thin-layer chromatography. Initial adipocyte size was 0.54, 1.06, and 0.96 micrograms of lipid per cell, respectively (normal 0.60), and the mean cell size decrease during weight reduction was 40%, all due to triglyceride mobilization. Adipocyte cholesterol and tocopherol content did not change significantly during weight reduction. These data are consistent with the concepts that triglycerides but not cholesterol or tocopherol are mobilized from the fat cell during up to 6 months of weight reduction and that independent mechanisms control the efflux of these adipocyte constituents.

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Specific radioactivity (SA) time curves of plasma and skin surface cholesterol collected at several skin areas were recorded in 10 patients on formula diets after single intravenous injections of radioactive cholesterol. Earliest detectable radioactivity on skin surface was found in 4-6 days; depending on the skin site, SA's peaked in 13-75 days. SA's of free cholesterol were almost always higher than those of esterified cholesterol. The general forms of the SA time curves were in keeping with the idea that plasma cholesterol is carried to the skin surface in association with the epidermal and sebaceous cells, whereby (a) cholesterol synthesized de novo is mixed with derived from plasma and (b) appearances of plasma cholesterol on the skin surface is delayed by a time factor that corresponds to the movement of epidermal and sebaceous cells from the basal layer to the skin surface. The shorter mean transit times of plasma cholesterol on skin areas rich in sebaceous glands (22-24 days on the head) than on those poor in these glands (38 days on forearms and 72 days on feet) suggest that cholesterol passes faster through the sebaceous glands than through the epidermis, and faster through thin than thick epidermis. The fraction of skin surface cholesterol (f) that is derived from plasma cholesterol was estimated by three independent methods, and comparable results were obtained. Values of f were lower on skin areas rich in sebaceous glands (0.29-0.46 on forehead) than on areas poor in these glands (0.41-0.70 for forearms; 0.60 on feet) and lower for esterified (0.27-0.33) than for free (0.39-0.48) cholesterol. These data suggest that higher proportions of sebaceous gland and of esterified cholesterol, respectively, are synthesized de novo than epidermal and of free cholesterol. In two patients it was possible to calculate that f of total skin surface cholesterol was 0.49 and 0.37, respectively, and that the maximum amount of plasma cholesterol lost through the skin was 29 and 22 mg/day, respectively. Knowing the total daily excretion of total neutral and acidic steroids in feces in these patients, and assuming a total daily urinary steroid excretion 50 mg, we estimated that no more than 3.2% of total steroid excretion occurred via the skin.