Deuterium metabolic imaging reveals greater liver fat contribution from lipogenesis in South Asian men than European men: a potential mechanism underlying elevated type 2 diabetes risk

Abstract Aims/hypothesis South Asian individuals are up to six times more likely to develop type 2 diabetes than individuals from other ethnic groups, often at a younger age and lower BMI. It has been shown that liver fat accumulates more readily in South Asian individuals, and this is thought to be a key driving factor contributing to the insulin resistance and diabetes in this population. However, 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 quantify DNL-derived liver fat and used it in a proof-of-concept case–control study, hypothesising that there would be greater liver fat contribution from DNL in South Asian individuals than in European individuals. Methods A total of seven South Asian and six European participants, matched for age and BMI, underwent deuterium magnetic resonance scans at baseline and after 5 days of 2 H water enrichment, from which the fractional and absolute amounts of liver fat from DNL (DNL MR ) were calculated. Proton magnetic resonance spectroscopy ( 1 H-MRS) and MRI were used to determine lipid quantity and composition. Results Our method allowed precise quantification of 2 H-labelled liver lipids (intraclass correlation coefficient [ICC]>0.956), which enabled us to accurately detect changes in liver fat due to DNL. Both fractional and absolute DNL MR were higher in South Asian participants than in European participants (both p =0.041). DNL MR correlated with liver fat content (fractional r s =0.874, absolute r s =0.888; both p =0.001), as well as the saturation ratio of both liver fat (fractional r s =0.692, absolute r s =0.748; both p <0.05) and visceral adipose tissue (fractional r s =0.648, absolute r s =0.708; both p <0.01). Liver fat content correlated with insulin resistance (HOMA-IR) ( r s =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 South Asian individuals. The novel methodology used to quantify DNL provides a powerful tool for studying DNL-derived liver fat in human metabolic disorders including diabetes.