Insulin Resistance in African-American and Caucasian Women: Differences in Lipotoxicity, Adipokines, and Gene Expression in Adipose Tissue and Muscle

Abstract

We tested whether African-American (AA) women are different from Caucasian women in regard to lipotoxicity, adipokines, and gene expression in adipose tissue and muscle. Insulin sensitivity (S(I)), plasma adipocytokine levels, intramyocellular lipid (IMCL), and the expression of candidate genes in adipose tissue and muscle were measured in AA and Caucasian women. This study was performed in an ambulatory general clinical research center. Subjects were healthy, nondiabetic AA and Caucasian women. There were no interventions. Comparison of S(I), IMCL, plasma adiponectin, and the expression of candidate genes regulating adipogenesis, lipogenesis, and inflammation in adipose tissue and muscle. AA had lower plasma adiponectin and IMCL when compared with Caucasian women with similar S(I). In sc adipose tissue (SAT), the expression of genes involved in adipogenesis including peroxisomal proliferator-activated receptor-gamma (PPARgamma) and lipin-1beta were also reduced in SAT of AA subjects (19%, P = 0.06, and 25%, P = 0.05, respectively). Similarly, 1-acylglycerol-3-phosphate acyltransferase 2 (AGPAT 2), stearoyl-coenzyme A desaturase-1 (SCD1), and CD36 mRNA expression was significantly reduced in SAT by 19, 54, and 28% respectively (P < 0.01 for all) in AA compared with Caucasian women. Yet the expression of CD68 in SAT was similar in both ethnic groups. Gene expression studies in muscle revealed a 31% reduction in expression of AGPAT 2 and a 72% reduction in SCD1 genes in AA. AA women demonstrated lower expression of several PPARgamma-responsive genes in adipose tissue, lower plasma adiponectin, and decreased IMCL levels as compared with Caucasians, which suggests that African-Americans may be protected from lipotoxicity. Together these data suggest significant ethnic differences in the pathophysiology of insulin resistance.