Increased de novo Lipogenesis is a Distinct Characteristic of Individuals with Nonalcoholic Fatty Liver Disease

By J. Lambert, M. Ramos-Roman, J. Browning, E. Parks. Gastroenterology, 2013

975 citations recorded by the source corpus.

BACKGROUND & AIMS: There have been few studies on the role of de novo lipogenesis in the development of nonalcoholic fatty liver disease (NAFLD). We used isotope analyses to compare de novo lipogenesis and fatty acid flux between individuals with NAFLD and those without, matched for metabolic factors (controls). METHODS: We studied subjects with metabolic syndrome and/or levels of alanine aminotransferase and aspartate aminotransferase >30 mU/L, using magnetic resonance spectroscopy to identify those with high levels (HighLF, n=13) or low levels of intrahepatic triacylglycerol (LowLF, n=11). Clinical and demographic information was collected from all participants, and insulin sensitivity was measured using the insulin-modified intravenous glucose tolerance test. Stable isotopes were administered and gas chromatography with mass spectrometry was used to analyze free (non-esterified) fatty acid (FFA) and triacylglycerol flux and lipogenesis. RESULTS: Individuals with HighLF (18.4%±3.6%) had higher plasma levels of FFA during the nighttime and concentrations of insulin than subjects with LowLF (3.1%±2.7%; P=.04 and P<.001, respectively). No differences were observed between groups in adipose flux of FFA (414±195 μmol/min for HighLF vs 358±105 μmol/min for LowLF; P=.41) or production of very low-density lipoprotein triacylglycerols from FFA (4.06±2.57 μmol/min vs 4.34±1.82 μmol/min; P=.77). By contrast, subjects with HighLF had more than 3-fold higher rates of de novo fatty acid synthesis than subjects with LowLF (2.57±1.53 μmol/min vs 0.78±0.42 μmol/min; P=.001). As a percentage of triacylglycerol palmitate, de novo lipogenesis was 2-fold higher in subjects with HighLF (23.2%±7.9% vs 10.1 %±6.7%; P<.001); this level was independently associated with the level of intrahepatic triacylglycerol (r=0.53; P=.007). CONCLUSIONS: By administering isotopes to individuals with NAFLD and control subjects, we confirmed that those with NAFLD increase synthesis of fatty acids. Subjects with NAFLD also had higher nocturnal plasma levels of FFA and did not suppress the contribution from de novo lipogenesis upon fasting. These findings indicate that lipogenesis might be a therapeutic target for NAFLD.

Subfields: Endocrinology, Diabetes and Metabolism, Epidemiology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/7afdb578fd737ddaa641e3bb4315c307856d0a05

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Citations in the corpus

Palmitic Acid: Physiological Role, Metabolism and Nutritional Implications (2017, background): “In an experiment where isolated rat hepatocytes were subjected to oxidative stress, Giron-Calle et al. (Giron-Calle et al., 1997) demonstrated that TAG could serve as an expendable FA reserve, providing a limited but very dynamic pool of PUFA for the resynthesis of PL (Giron-Calle et al., 1997).”
Insulin resistance drives hepatic de novo lipogenesis in nonalcoholic fatty liver disease. (2019, methodology): “Studies using this approach reported that DNL accounts for 15% to 26% of IHTGpalmitate production in people with NAFLD (12, 14-16) and 1% to 10% of IHTG-palmitate production in people who are either lean or obese with normal IHTG content (14, 17-20).”
Molecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease (2018, background): “7%, n = 11) while being matched for adiposity and circulating lipids [39].”
The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD). (2016, neutral): “levels of FFAs [25].”