title: Increased de novo lipogenesis is a distinct characteristic of individuals with nonalcoholic fatty liver disease.
abstract: OBJECTIVE
  There have been few studies of 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 subjects 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 (LowLF, n = 11) of liver fat. 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 (nonesterified) fatty acid (FFA) and triacylglycerol flux and lipogenesis.
  
  
  RESULTS
  Subjects with HighLF (18.4% ± 3.6%) had higher plasma levels of FFAs during the nighttime and higher 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 FFAs (414 ± 195 μmol/min for HighLF vs 358 ± 105 μmol/min for LowLF; P = .41) or production of very-low-density lipoprotein triacylglycerol from FFAs (4.06 ± 2.57 μmol/min vs 4.34 ± 1.82 μmol/min; P = .77). In 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 subjects with NAFLD and control subjects, we confirmed that those with NAFLD have increased synthesis of fatty acids. Subjects with NAFLD also had higher nocturnal plasma levels of FFAs and did not suppress the contribution from de novo lipogenesis on fasting. These findings indicate that lipogenesis might be a therapeutic target for NAFLD.
authors: Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, Texas.
authors: Jennifer E
authors: JE
authors: Lambert
authors: Division of Endocrinology, University of Texas Southwestern Medical Center, Dallas, Texas.
authors: Maria A
authors: MA
authors: Ramos-Roman
authors: Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, Texas.
authors: Jeffrey D
authors: JD
authors: Browning
authors: Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, Texas. Electronic address: Parksej@missouri.edu.
authors: Elizabeth J
authors: EJ
authors: Parks
mesh_terms: D016022:Case-Control Studies; D015897:Comorbidity; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005234:Fatty Liver / Q000453:epidemiology / Q000503:physiopathology*; D005260:Female; D006801:Humans; D006949:Hyperlipidemias / Q000453:epidemiology / Q000503:physiopathology*; D050155:Lipogenesis / Q000502:physiology*; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D024821:Metabolic Syndrome / Q000503:physiopathology; D065626:Non-alcoholic Fatty Liver Disease
chemical_list: D005230:Fatty Acids, Nonesterified
keywords: Diabetes; Fatty Acid Kinetics; Lipid Metabolism; Obesity