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

Objectives: 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. Design: Insulin sensitivity (SI), plasma adipocytokine levels, intramyocellular lipid (IMCL), and the expression of candidate genes in adipose tissue and muscle were measured in AA and Caucasian women. Setting: This study was performed in an ambulatory general clinical research center. Subjects: Subjects were healthy, nondiabetic AA and Caucasian women. Interventions: There were no interventions. Main Outcome Measures: Comparison of S-I, IMCL, plasma adiponectin, and the expression of candidate genes regulating adipogenesis, lipogenesis, and inflammation in adipose tissue and muscle. Results: 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 (PPAR gamma) and lipin-1 beta 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-coenzymeAdesaturase-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. Conclusion: AA women demonstrated lower expression of several PPAR gamma-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. (J Clin Endocrinol Metab 95: 4441-4448, 2010)