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

Abstract

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

Biliary lipid secretion in cholesterol gallstone disease. The effect of cholecystectomy and obesity.

“…Instead, the cholesterol secretion rate is increased and directly related to the extent of obesity. This high cholesterol output into bile agrees with the increased cholesterol turnover documented in obesity (43,44), the source of which presumably arises in the liver or intestine rather than from adipose tissue (45).…”

Regulation of ABCA1 expression and cholesterol efflux during adipose differentiation of 3T3-L1 cells

“…Rather, it has been suggested that adipose tissue might be a sink for circulating cholesterol, which could help to buffer the high levels of circulating cholesterol frequently found in obese states. Because adipose tissue cholesterol content is strongly correlated with fat cell size in humans or rodents (23,25), we have proposed that intracellular cholesterol in adipocytes might act as a cell size-dependent intracellular signal, and might serve as a sensor for the level of intracellular triglyceride stores (28). In that view, the low ability of adipocytes for cholesterol efflux fits with cholesterol being a signaling molecule in fat cells, linked to the levels of energy stores.…”

“…Thus, in addition to its well-known function in the managing of energy stores in the form of triacylglycerol, adipose tissue also contains the largest pool of cholesterol in the body. In fat tissue, cholesterol synthesis is extremely low (25), and most cholesterol is taken up from the circulation and is deposited in the free nonesterified form. In this regard, cholesterol storage in fat can be considered a "buffering" process, which might help to avoid hypercholesterolemia.…”

Parameters of the three-pool model of the turnover of plasma cholesterol in normal and hyperlipidemic humans.

“…The positive correlation between Ms and adiposity is consistent with the finding that adipose tissue cholesterol appears to be an important part of the most slowly turning over compartment, pool 3 (34). Schreibman and Dell have reported recently cholesterol turnover studies of 10-20 wk duration in which a threepool model was fit simultaneously to both plasma and adipocyte specific activity-time curves (34). In five of six subjects, the kinetics of adipose tissue cholesterol closely fit that of the slowly turning over pool 3.…”