Deuterium metabolic imaging reveals greater liver fat contribution from lipogenesis in South Asians than Europeans: A potential mechanism underlying elevated type 2 diabetes risk

Abstract

Aim/Hypothesis South Asians (SA) are up to six times more likely to develop type 2 diabetes, often at a younger age and lower BMI than other ethnic groups. It has been shown that liver fat accumulates more readily in SA, and this is thought to be a key driving factor contributing to the insulin resistance and diabetes in SA but the mechanisms underlying this phenomenon remain unclear. Understanding the role of de novo lipogenesis (DNL) in liver fat accumulation has been hampered by a lack of non-invasive techniques to quantify DNL-derived liver fat. We developed a method to do this and used it in a proof-of-concept case-control study hypothesizing a greater liver fat contribution from DNL in SA than Europeans (E). Methods 7 SA and 6 E subjects matched for age and body mass index had deuterium magnetic resonance scans at baseline and after 5 days 2H water enrichment, from which the fractional and absolute amount of liver fat from DNL (DNLMR) were calculated. 1H MRS and MRI provided lipid quantity and composition. Results We first showed that our method was able to make precise 2H liver lipid measurements (ICC>0.95) which enabled us to accurately detect changes due to DNL. Both fractional and absolute DNLMR were higher in SA vs E (both p=0.04). DNLMR correlated with liver fat content (fractional rs=0.87, absolute rs=0.88; both p=0.001), as well as the saturation ratio of both liver fat (rs=0.75) and visceral adipose tissue (rs=0.71, both p<0.01). Liver fat content correlated with insulin resistance (HOMA-IR) (rs=0.659, p=0.014). Conclusions/interpretation DNL or related factors may play a pivotal role in driving the increased liver fat and risk of diabetes in SA. The novel methodology used to quantify DNL provides a powerful tool for studying DNL-derived liver fat in human metabolic disorders including diabetes.