Background and aim: Hormone sensitive lipase (HSL) is the rate-limiting enzyme in triglyceride intracellular lipolysis, generating free fatty acids for energy utilisation. HSL is also expressed in pancreatic beta-cells where its activity may affect insulin secretion. We previously identified an HSL promoter variant, -60C > G, which in vitro exhibits 40% reduced promoter activity.
Methods and results: In this study we examined the association of the HSL -60C > G on fasting lipid, insulin and glucose levels and the response to an oral fat tolerance test and an oral glucose tolerance test in 744 healthy young men participating in the second European Atherosclerosis Study. There was no case control difference in frequency of the rare -60G allele, however there was a North-to-South gradient in the frequency of the -60G allele, ranging from 0.037 (95% CI 0.01-0.07) in the Baltic regions to 0.087 (95% CI 0.05-0.12) in the South of Europe. When the group was analysed as a whole, there was no significant difference in fasting lipid or glucose values, body mass index, waist/hip ratio or blood pressure and no significant heterogeneity between cases and controls. There was, however, a significant association with fasting insulin measures [-60CC (n = 608) 11.95 mU/L vs -60 CG + GG (n = 79) 10.62 mU/L p = 0.01] and with the homeostasis model assessment of insulin resistance (HOMA-IR) (p = 0.04) and the homeostatic assessment of beta-cells function (HOMA-B); (p = 0.008).
Conclusion: Even in these healthy young men, HSL-60 C > G allele was associated with effects on fasting insulin measures, and differences in insulin resistance and beta-cells function.