Sex-Specific Differences in Hepatic Fat Oxidation and Synthesis May Explain the Higher Propensity for NAFLD in Men

J Clin Endocrinol Metab. 2015 Dec;100(12):4425-33. doi: 10.1210/jc.2015-2649. Epub 2015 Sep 28.


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.

Participants and methods: 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.

Results: 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).

Conclusions: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Hydroxybutyric Acid / metabolism
  • Adult
  • Aged
  • Carbon Dioxide / metabolism
  • Dietary Fats / metabolism
  • Fasting / metabolism
  • Fatty Acids / biosynthesis
  • Female
  • Humans
  • Lipid Metabolism*
  • Lipids / biosynthesis*
  • Lipogenesis / genetics
  • Lipoproteins, VLDL / blood
  • Liver / metabolism*
  • Male
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease / metabolism*
  • Oxidation-Reduction
  • Palmitates / metabolism
  • Postprandial Period
  • Sex Characteristics
  • Triglycerides / blood


  • Dietary Fats
  • Fatty Acids
  • Lipids
  • Lipoproteins, VLDL
  • Palmitates
  • Triglycerides
  • Carbon Dioxide
  • 3-Hydroxybutyric Acid