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  • Title: Hepatic Fatty Acid Balance and Hepatic Fat Content in Humans With Severe Obesity.
    Author: Lytle KA, Bush NC, Triay JM, Kellogg TA, Kendrick ML, Swain JM, Gathaiya NW, Hames KC, Jensen MD.
    Journal: J Clin Endocrinol Metab; 2019 Dec 01; 104(12):6171-6181. PubMed ID: 31408176.
    Abstract:
    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.
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