Fatty acid synthase gene expression in human adipose tissue: association with obesity and type 2 diabetes

Aims/hypothesis Increased expression and activity of the lipogenic pathways in adipose tissue may contribute to the development of obesity. As a central enzyme in lipogenesis, the gene encoding fatty acid synthase (FASN) was identified as a candidate gene for determining body fat. In the present study we tested the hypothesis that increased FASN expression links metabolic alterations of excess energy intake, including hyperinsulinaemia, dyslipidaemia and altered adipokine profile to increased body fat mass. Subjects and methods In paired samples of visceral and subcutaneous adipose tissue from 196 participants (lean or obese), we investigated whether FASN mRNA expression (assessed by PCR) in adipose tissue is increased in obesity and related to visceral fat accumulation, measures of insulin sensitivity (euglycaemic-hyperinsulinaemic clamp) and glucose metabolism. Results FASN mRNA expression was increased by 1.7-fold in visceral vs subcutaneous fat. Visceral adipose tissue FASN expression was correlated with FASN protein levels, subcutaneous FASN expression, visceral fat area, fasting plasma insulin, serum concentrations of IL-6, leptin and retinol-binding protein 4 (RBP4), and inversely with measures of insulin sensitivity, independently of age, sex and BMI. Moreover, we found significant correlations between FASN expression and markers of renal function, including serum creatinine and urinary albumin excretion. Conclusions/interpretation Increased FASN gene expression in adipose tissue is linked to visceral fat accumulation, impaired insulin sensitivity, increased circulating fasting insulin, IL-6, leptin and RBP4, suggesting an important role of lipogenic pathways in the causal relationship between consequences of excess energy intake and the development of obesity and type 2 diabetes.