Hepatic Fatty Acid Balance and Hepatic Fat Content in Humans With Severe Obesity

J Clin Endocrinol Metab. 2019 Dec 1;104(12):6171-6181. doi: 10.1210/jc.2019-00875.


Objective: Nonalcoholic fatty liver disease can lead to hepatic inflammation/damage. Understanding the physiological mechanisms that contribute to excess hepatic lipid accumulation may help identify effective treatments.

Design: We recruited 25 nondiabetic patients with severe obesity scheduled for bariatric surgery. To evaluate liver export of triglyceride fatty acids, we measured very-low-density lipoprotein (VLDL)-triglyceride secretion rates the day prior to surgery using an infusion of autologous [1-14C]triolein-labeled VLDL particles. Ketone body response to fasting and intrahepatic long-chain acylcarnitine concentrations were used as indices of hepatic fatty acid oxidation. We measured intraoperative hepatic uptake rates of plasma free fatty acids using a continuous infusion of [U-13C]palmitate, combined with a bolus dose of [9,10-3H]palmitate and carefully timed liver biopsies. Total intrahepatic lipids were measured in liver biopsy samples to determine fatty liver status. The hepatic concentrations and enrichment from [U-13C]palmitate in diacylglycerols, sphingolipids, and acyl-carnitines were measured using liquid chromatography/tandem mass spectrometry.

Results: Among study participants with fatty liver disease, intrahepatic lipid was negatively correlated with VLDL-triglyceride secretion rates (r = -0.92, P = 0.01) but unrelated to hepatic free fatty acid uptake or indices of hepatic fatty acid oxidation. VLDL-triglyceride secretion rates were positively correlated with hepatic concentrations of saturated diacylglycerol (r = 0.46, P = 0.02) and sphingosine-1-phosphate (r = 0.44, P = 0.03).

Conclusion: We conclude that in nondiabetic humans with severe obesity, excess intrahepatic lipid is associated with limited export of triglyceride in VLDL particles rather than increased uptake of systemic free fatty acids.

Publication types

  • Clinical Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Bariatric Surgery
  • Fatty Acids / metabolism*
  • Fatty Acids, Nonesterified / blood
  • Female
  • Humans
  • Lipid Metabolism*
  • Lipoproteins, VLDL / blood
  • Liver / metabolism*
  • Liver / pathology
  • Male
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease / etiology
  • Non-alcoholic Fatty Liver Disease / metabolism
  • Obesity, Morbid / complications
  • Obesity, Morbid / metabolism*
  • Obesity, Morbid / pathology
  • Obesity, Morbid / surgery
  • Sphingolipids / metabolism
  • Triglycerides / blood
  • Young Adult


  • Fatty Acids
  • Fatty Acids, Nonesterified
  • Lipoproteins, VLDL
  • Sphingolipids
  • Triglycerides
  • very low density lipoprotein triglyceride