Dataset Information

Fasting hepatic de novo lipogenesis is not reliably assessed using circulating fatty acid markers.

ABSTRACT:

Background

Observational studies often infer hepatic de novo lipogenesis (DNL) by measuring circulating fatty acid (FA) markers; however, it remains to be elucidated whether these markers accurately reflect hepatic DNL.

Objectives

We investigated associations between fasting hepatic DNL and proposed FA markers of DNL in subjects consuming their habitual diet.

Methods

Fasting hepatic DNL was assessed using 2H2O (deuterated water) in 149 nondiabetic men and women and measuring the synthesis of very low-density lipoprotein triglyceride (VLDL-TG) palmitate. FA markers of blood lipid fractions were determined by gas chromatography.

Results

Neither the lipogenic index (16:0/18:2n-6) nor the SCD index (16:1n-7/16:0) in VLDL-TG was associated with isotopically assessed DNL (r = 0.13, P = 0.1 and r = -0.08, P = 0.35, respectively). The relative abundances (mol%) of 14:0, 16:0, and 18:0 in VLDL-TG were weakly (r ≤ 0.35) associated with DNL, whereas the abundances of 16:1n-7, 18:1n-7, and 18:1n-9 were not associated. When the cohort was split by median DNL, only the abundances of 14:0 and 18:0 in VLDL-TG could discriminate between subjects having high (11.5%) and low (3.8%) fasting hepatic DNL. Based on a subgroup, FA markers in total plasma TG, plasma cholesteryl esters, plasma phospholipids, and red blood cell phospholipids were generally not associated with DNL.

Conclusions

The usefulness of circulating FAs as markers of hepatic DNL in healthy individuals consuming their habitual diet is limited due to their inability to discriminate clearly between individuals with low and high fasting hepatic DNL.

SUBMITTER: Rosqvist F

PROVIDER: S-EPMC6367991 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUNDAn increase in intrahepatic triglyceride (IHTG) is the hallmark feature of nonalcoholic fatty liver disease (NAFLD) and is decreased by weight loss. Hepatic de novo lipogenesis (DNL) contributes to steatosis in individuals with NAFLD. The physiological factors that stimulate hepatic DNL and the effect of weight loss on hepatic DNL are not clear.METHODSHepatic DNL, 24-hour integrated plasma insulin and glucose concentrations, and both liver and whole-body insulin sensitivity were determined in individuals who were lean (n = 14), obese with normal IHTG content (n = 26), or obese with NAFLD (n = 27). Hepatic DNL was assessed using the deuterated water method corrected for the potential confounding contribution of adipose tissue DNL. Liver and whole-body insulin sensitivity was assessed using the hyperinsulinemic-euglycemic clamp procedure in conjunction with glucose tracer infusion. Six subjects in the obese-NAFLD group were also evaluated before and after a diet-induced weight loss of 10%.RESULTSThe contribution of hepatic DNL to IHTG-palmitate was 11%, 19%, and 38% in the lean, obese, and obese-NAFLD groups, respectively. Hepatic DNL was inversely correlated with hepatic and whole-body insulin sensitivity, but directly correlated with 24-hour plasma glucose and insulin concentrations. Weight loss decreased IHTG content, in conjunction with a decrease in hepatic DNL and 24-hour plasma glucose and insulin concentrations.CONCLUSIONSThese data suggest hepatic DNL is an important regulator of IHTG content and that increases in circulating glucose and insulin stimulate hepatic DNL in individuals with NAFLD. Weight loss decreased IHTG content, at least in part, by decreasing hepatic DNL.TRIAL REGISTRATIONClinicalTrials.gov NCT02706262.FUNDINGThis study was supported by NIH grants DK56341 (Nutrition Obesity Research Center), DK20579 (Diabetes Research Center), DK52574 (Digestive Disease Research Center), and RR024992 (Clinical and Translational Science Award), and by grants from the Academy of Nutrition and Dietetics Foundation, the College of Natural Resources of UCB, and the Pershing Square Foundation.