Cited by 1,069Liver Disease Diagnosis and TreatmentLipid metabolism and biosynthesisLipid metabolism and disorders

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Increased De Novo Lipogenesis Is a Distinct Characteristic of Individuals With Nonalcoholic Fatty Liver Disease

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Lambert, Jennifer E., Ramos–Roman, Maria A., Browning, Jeffrey D., Parks, Elizabeth J.·2014·Gastroenterology

DOI 10.1053/j.gastro.2013.11.049PMC PMC6276362

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Abstract

Background & aims 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.

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Effects of UBE3A on Cell and Liver Metabolism through the Ubiquitination of PDHA1 and ACAT1
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Zhuyu Pill Alleviates Nonalcoholic Fatty Liver Disease by Regulating Bile Acid Metabolism through the Gut–Liver Axis
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Nonalcoholic Fatty Liver Disease and the Intestinal Microbiome: An Inseparable Link
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“19 Activated insulin receptors substrate 2 (IRS-2) influences DNL by regulating of SREBP-1c.”
Background
Association between Impaired Ketogenesis and Metabolic-Associated Fatty Liver Disease
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Cardiovascular Risk Reduction in Metabolic Dysfunction-Associated Steatotic Liver Disease and Metabolic Dysfunction-Associated Steatohepatitis
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Self-citation
TTC39B destabilizes retinoblastoma protein promoting hepatic lipogenesis in a sex-specific fashion
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Background
Is the Fatty Acids Profile in Blood a Good Predictor of Liver Changes? Correlation of Fatty Acids Profile with Fatty Acids Content in the Liver
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Increased incidence of non‐alcoholic fatty liver disease in male rat offspring exposed to fluoxetine during fetal and neonatal life involves the NLRP3 inflammasome and augmented de novo hepatic lipogenesis
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Molecular Genealogy of Metabolic-associated Hepatocellular Carcinoma
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“93,94 This increase in lipogenesis may provide the necessary substrates for cell membrane formation and energy production in intrahepatic tumor cells.”
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“Hepatic DNL is increased in people with MASLD 41 and those with peripheral insulin resistance.”
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BackgroundInfluential
Native polypeptide vglycin prevents nonalcoholic fatty liver disease in mice by activating the AMPK pathway
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Non-alcoholic Fatty Liver Disease and Depression: Evidence for Genotype × Environment Interaction in Mexican Americans
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Apigenin Suppresses MED28-Mediated Cell Growth in Human Liver Cancer Cells
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Obesity and Nonalcoholic Fatty Liver Disease
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The Tailgate Study: Differing metabolic effects of a bout of excessive eating and drinking
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Value of MRI and MRS fat measurements to complement conventional screening methods for childhood obesity
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“Furthermore, impaired hepatic fatty acid oxidation and a decrease in proteins inducing lipid oxidation, eg, adiponectin, result in accumulation of fat within the liver.(6) Together with altered glucose metabolism, this overflow of free fatty acids to the liver is responsible for the upregulation of proinflammatory sig…”
Background
Exploring the interplay between metabolic dysfunction-associated fatty liver disease and gut dysbiosis: Pathophysiology, clinical implications, and emerging therapies
Al‐Busafi, S. A., Alwassief, A., Madian, A., Atalla, H., Alboraie, M. A. A., Elbahrawy, A., & Eslam, M. (2025) · World Journal of Hepatology · doi:10.4254/wjh.v17.i8.108730 · Cited by 10
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Karapanagiotidi, F., Boutari, C., & Sinakos, E. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27041933 · Cited by 10
Association with the plasma atherogenic index with hepatic steatosis and fibrosis in the US population
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“[32,37] When IR manifests in an organism, TG accumulates within hepatocytes within liver.”
Background
Glycated haemoglobin is a major predictor of disease severity in patients with NAFLD
Colosimo, S., Miller, H., Koutoukidis, D. A., Marjot, T., Tan, G. D., Harman, D. J., Aithal, G. P., Manousou, P., Forlano, R., Parker, R., et al. (2024) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2024.111820 · Cited by 11
Zhimu-Huangbai herb-pair ameliorates hepatic steatosis in mice by regulating IRE1α/XBP1s pathway to inhibit SREBP-1c
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“Although low lipogenic rates mimic human physiology, 5,7,56,57 such low rates also impose a limitation on the dynamic range of our measurements.”
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“Furthermore, individuals with MASLD exhibit increased DNL, thereby exacerbating hepatic steatosis [45,46].”
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BackgroundInfluential
Combined Transcriptomic and Lipidomic Analysis Reveals Dysregulated Genes Expression and Lipid Metabolism Profiles in the Early Stage of Fatty Liver Disease in Rats
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“Several studies report that the content of free FAs in plasma increases in patients with NAFLD (24, 33).”
Background
Assessing the validity of plasma phospholipid fatty acids as biomarkers of dairy fat intake using data from a randomized controlled intervention trial
Bethancourt, H. J., Schmidt, K. A., Cromer, G., Burhans, M. S., Kuzma, J. N., Hagman, D. K., Fernando, I., Murray, M., Utzschneider, K. M., Holte, S., et al. (2022) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqac029 · Cited by 10

Authors: Lambert, J. E., Ramos–Roman, M. A., Browning, J. D., & Parks, E. J.
Affiliations: The University of Texas Southwestern Medical Center (US)
Corresponding author: Parks, Elizabeth J.
ORCID: Parks, Elizabeth J.
Venue: Gastroenterology
Publisher: Elsevier BV
Published: 2014-03
Volume: 146
Issue: 3
Pages: 726-735
ISSN: 0016-5085 (ISSN-L)
DOI: 10.1053/j.gastro.2013.11.049
PMC: PMC6276362
OpenAlex: W2139351004
Cited by: 1,069
References: 58
Citations by year: 2026: 67 · 2025: 111 · 2024: 110 · 2023: 108 · 2022: 124 · 2021: 111 · 2020: 106 · 2019: 92 · 2018: 75 · 2017: 47 · 2016: 49 · 2015: 45 · 2014: 23
FWCI: 28.42
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Gastroenterology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health (RL1DK081187, UL1DE019584, UL1-RR024982)
National Center for Advancing Translational Sciences (RL1DK081187, UL1DE019584, UL1-RR024982)
Topics: Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
Keywords: de novo lipogenesis, non-alcoholic fatty liver disease, fatty acid synthesis, triglyceride synthesis, liver fat, metabolic syndrome, insulin sensitivity, stable isotope tracer studies, hepatic lipid metabolism, insulin
MeSH terms: Fatty Acids, Nonesterified, Fatty Liver, Female, Humans, Hyperlipidemias, Liver, Magnetic Resonance Imaging, Male, Comorbidity, Case-Control Studies, Metabolic Syndrome, Lipogenesis, Non-alcoholic Fatty Liver Disease

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Increased De Novo Lipogenesis Is a Distinct Characteristic of Individuals With Nonalcoholic Fatty Liver Disease

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