1Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, UK.
2Oxford Centre for Clinical Magnetic Resonance Research, University of Oxford, Oxford, UK.
3Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, UK.
4National Institute for Health Research Oxford Biomedical Research Centre, Oxford University Hospital Trusts, UK.
CONTEXT AND OBJECTIVE:
In most populations a greater proportion of men have hepatic steatosis than women. Sex-specific differences in hepatic dietary fatty acid (FA) metabolism have not been well characterized. We compared fasting and postprandial hepatic FA synthesis (de novo lipogenesis (DNL)) and oxidation in men and women.
and Methods: Fasting and postprandial hepatic FA metabolism was studied in twenty-two healthy men (n=11) and women with similar age, BMI and liver fat content using metabolic substrates labelled with stable-isotope tracers (2H2O and [U13C]palmitate). Dietary FA oxidation was assessed by appearance of 13C into plasma 3-hydroxybutyrate (3OHB) and breath CO2 as markers of liver and whole-body FA oxidation, respectively.
Despite similar liver fat content, fasting and postprandial plasma triacylglycerol (TG) concentrations were significantly (P<0.05) higher in men compared to women. The appearance of 13C from dietary FA into plasma 3OHB and breath CO2 was greater (P<0.05) in women compared to men. Although the contribution of DNL into very low density lipoprotein (VLDL)-TG was similar (∼10%) in the fasting state, there was a divergence in pattern over the course of the study, with men maintaining a higher contribution of DNL to VLDL-TG than women (P=0.006 time x sex interaction).
The combination of lower dietary FA oxidation and a prolonged increase in DNL observed in men may represent partitioning of FA into esterification and storage pathways within the liver leading to greater VLDL-TG production and predispose to the sex difference in hepatic steatosis.