Cardiovascular risk score is linked to subcutaneous adipocyte size and lipid metabolism

OBJECTIVE: Although white adipose tissue mass and distribution correlates with cardiovascular disease, the fat cell-specific perturbations underlying this association are not known. We determined the relationship between adipocyte size and lipid metabolism with cardiovascular risk. DESIGN/SUBJECTS: Adipocyte size as well as spontaneous (basal) and hormone-stimulated effects on adipocyte lipid metabolism (lipolysis and lipogenesis) were investigated in abdominal subcutaneous adipose tissue of 304 men and 775 women. Subjects were classified into five categories according to Adult Treatment Panel III (ATPIII) metabolic syndrome criteria. RESULTS: Adipocyte size increased with increasing ATPIII score (P < 0.0001). For lipolysis, there was a gradual increase in basal and catecholamine-stimulated lipolysis and a decrease in insulin-mediated inhibition of stimulated lipolysis with ATPIII (P < 0.0001). In contrast, the lipolytic action of atrial natriuretic peptide was similar between ATPIII classes. Basal and insulin-stimulated lipogenesis decreased with increasing score (P < 0.0001). Circulating free fatty acid levels were 50% higher in the top risk category (4-5) compared with the lowest score (P < 0.0001). Fat cell size correlated positively with increasing ATPIII score and lipolysis but negatively with lipogenesis. All these differences were independent of age, sex and body weight status (P < 0.0001 to 0.02 after correction). When all functional measures were put together, maximum insulin-stimulated lipogenesis, insulin-antilipolytic sensitivity and basal lipolysis together explained about 20% in the variation of ATPIII in score. CONCLUSIONS: Independently of sex, age and body weight status, a high cardiovascular risk score associates with increased circulating free fatty acid levels and hormone-specific alterations of lipolysis/lipogenesis in enlarged subcutaneous fat cells.