Relationship between Human Adipose Tissue Agouti and Fatty Acid Synthase (FAS)

The human homologue of the murine obesity gene, agouti, is expressed in adipose tissue. We have shown that recombinant agouti protein regulates adipocyte lipogenesis and lipolysis coordinately and promotes lipid storage via a [Ca.sup.2+]-dependent mechanism in vitro, which may contribute to agouti-induced obesity. However, little is known about agouti's physiologic function in humans. We first studied the agouti content in human mature adipocytes vs. preadipocytes. The agouti content of human mature adipocytes was five times as abundant as in preadipocytes (19.18 [+ or -] 2.46 vs. 4.07 [+ or -] 0.51 pg/[micro]g protein, P [is less than] 0.005), suggesting that agouti is up-regulated during adipocyte differentiation. We next studied the relationship of agouti mRNA and protein to fatty acid synthase (FAS) mRNA and activity in adipose tissue obtained from nonobese and mildly obese patients (body mass index range, 21-31 kg/[m.sup.2]). Agouti protein was correlated with FAS activity (r = 0.782, P [is less than] 0.005). Similarly, human adipose tissue agouti mRNA level was also correlated with FAS mRNA level (r = 0.846, P [is less than] 0.001). These data suggest that agouti may be another adipocyte-produced factor that modulates adipocyte lipid metabolism via a paracrine/autocrine mechanism. J. Nutr. 130: 2478-2481, 2000. KEY WORDS: * agouti * fatty acid synthase * adipose tissue * adipocyte differentiation * obesity * humans