Abstract

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. Fasting and postprandial hepatic FA metabolism was studied in 22 healthy men (n = 11) and women with similar age, body mass index, and liver fat content using metabolic substrates labeled with stable-isotope tracers ((2)H2O and [U(13)C]palmitate). Dietary FA oxidation was assessed by appearance of (13)C into plasma 3-hydroxybutyrate 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 < .05) higher in men compared with women. The appearance of (13)C from dietary FA into plasma 3-hydroxybutyrate and breath CO2 was greater (P < .05) in women compared with 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 = .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.

Highlights

  • Despite similar liver fat content, fasting and postprandial plasma triacylglycerol (TG) concentrations were significantly (P Ͻ .05) higher in men compared with women

  • The contribution of de novo lipogenesis (DNL) into very low-density lipoprotein (VLDL)-TG was similar (ϳ10%) 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 ϭ .006 time x sex interaction)

  • The combination of lower dietary fatty acid (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. (J Clin Endocrinol Metab 100: 4425– 4433, 2015)

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Summary

Introduction

Despite similar liver fat content, fasting and postprandial plasma triacylglycerol (TG) concentrations were significantly (P Ͻ .05) higher in men compared with women. The appearance of 13C from dietary FA into plasma 3-hydroxybutyrate and breath CO2 was greater (P Ͻ .05) in women compared with men. The contribution of DNL into very low-density lipoprotein (VLDL)-TG was similar (ϳ10%) 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 ϭ .006 time x sex interaction)

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