Fatty acid handling protein expression in adipose tissue, fatty acid composition of adipose tissue and serum, and markers of insulin resistance

Objective: Proteins involved in cellular fatty acid (FA) uptake and metabolism may be of relevance in the context of disturbed FA metabolism associated with insulin resistance. Therefore this study investigated relationships between FA handling protein mRNA expression in adipose tissue, FA composition of adipose tissue and serum, and markers of insulin resistance. Subjects: 75 subjects with a range of insulin sensitivities recruited from a cohort of 294 healthy 63-year-old Swedish men. Measurements: Anthropometric and biochemical variables (e.g. waist-hip-ratio (WHR) and homeostasis model assessment (HOMA) index of insulin sensitivity), FA composition of the subcutaneous (s.c.) gluteal adipose tissue, serum nonesterified FA (NEFA) and serum phospholipid compartments (by gas-liquid chromatography; n = 294), and mRNA levels of FA handling proteins (adipocyte and keratinocyte lipid binding proteins, fatty acid transport protein (FATP) -1 and -4, CD36/fatty acid translocase, plasma membrane fatty acid binding protein, and acyl-CoA synthase-1 (ACS1)) in s.c. gluteal adipose tissue (by quantitative real-time polymerase chain reaction; n = 75). Results: ACS1 expression was negatively correlated with measures of insulin resistance and central obesity ( ACS1 versus HOMA: r = -0.28, P < 0.05; ACS1 versus WHR: r = -0.23, P < 0.05), with an opposite trend for FATP4. Further analysis of ACS1 expression levels revealed correlations with adipose tissue 16:0 (r = -0.27, P < 0.05) and NEFA 16: 1 (r = 0.29, P < 0.05), FA composition variables which in turn correlated with HOMA index (r = 0.39, P < 0.001 and r = -0.23, P < 0.05, respectively, n 75). Moreover, NEFA 16:1 predicted ACS1 expression independently of HOMA, WHR and adipose tissue 16:0 in multiple regression analysis (standardized coefficient = 0.27, P < 0.05). Conclusion: Significant associations were found between measures of insulin sensitivity, adipose tissue FA handling protein expression, and specific FA composition variables. Although causal relationships could not be identified these findings suggest a role of FA handling proteins in relation to insulin sensitivity, via their involvement in FA trafficking and metabolism. In particular they indicate links between ACS1 activity, the distribution of 16:0 and 16:1, and insulin sensitivity, which may be of physiological relevance.