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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Hepatic Mitochondrial Oxidative Metabolism and Lipogenesis Synergistically Adapt to Mediate Healthy Embryonic-to-Neonatal Transition in Chicken
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Huangqin decoction alleviates lipid metabolism disorders and insulin resistance in nonalcoholic fatty liver disease by triggering Sirt1/NF-κB pathway
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Low Screening Rates Despite a High Prevalence of Significant Liver Fibrosis in People with Diabetes from Primary and Secondary Care
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Stable isotope-based flux studies in nonalcoholic fatty liver disease
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Hyperoside modulates bile acid and fatty acid metabolism, presenting a potentially promising treatment for non-alcoholic fatty liver disease
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Helminth infection and helminth-derived products: A novel therapeutic option for non-alcoholic fatty liver disease
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Branched-chain amino acids alter cellular redox to induce lipid oxidation and reduce de novo lipogenesis in the liver
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Amorphous solid dispersion augments the bioavailability of phloretin and its therapeutic efficacy via targeting mTOR/SREBP-1c axis in NAFLD mice
Chhimwal, J., Dhritlahre, R. K., Anand, P., Ruchika, Patial, V., Saneja, A., & Padwad, Y. S. (2023) · Biomaterials Advances · doi:10.1016/j.bioadv.2023.213627 · Cited by 17
Mitigating Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD): The Role of Bioactive Phytoconstituents in Indian Culinary Spices
Barbhuiya, P. A., Ahmed, A., Dutta, P. P., Sen, S., & Pathak, M. P. (2025) · Current Nutrition Reports · doi:10.1007/s13668-024-00598-w · Cited by 18
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Isocaloric manipulation of macronutrients within a high-carbohydrate/moderate-fat diet induces unique effects on hepatic lipogenesis, steatosis and liver injury
Pierce, A. A., Duwaerts, C. C., Soon, R. K., Siao, K., Grenert, J. P., Fitch, M. D., Hellerstein, M. K., Beysen, C., Turner, S., & Maher, J. J. (2015) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2015.10.020 · Cited by 17
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Carbohydrates and diet patterns in nonalcoholic fatty liver disease in children and adolescents
Sekkarie, A., Welsh, J. A., & Vos, M. B. (2018) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0000000000000476 · Cited by 17
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Stimulation of endogenous pulsatile growth hormone secretion by activation of growth hormone secretagogue receptor reduces the fat accumulation and improves the insulin sensitivity in obese mice
Huang, Z., Lu, X., Huang, L., Zhang, C., Veldhuis, J. D., Cowley, M. A., & Chen, C. (2020) · The FASEB Journal · doi:10.1096/fj.202001924rr · Cited by 16
Intact Fasting Insulin Identifies Nonalcoholic Fatty Liver Disease in Patients Without Diabetes
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Artemether Ameliorates Non-Alcoholic Steatohepatitis by Repressing Lipogenesis, Inflammation, and Fibrosis in Mice
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BackgroundInfluential
Childhood Fructoholism and Fructoholic Liver Disease
Ribeiro, A., Igual‐Perez, M., Silva, E. S., & Sokal, E. M. (2018) · Hepatology Communications · doi:10.1002/hep4.1291 · Cited by 17
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Beta-3-adrenergic Receptor rs4994 Polymorphism Is a Potential Biomarker for the Development of Nonalcoholic Fatty Liver Disease in Overweight/Obese Individuals
Sakamoto, Y., Oniki, K., Kumagae, N., Morita, K., Otake, K., Ogata, Y., & Saruwatari, J. (2019) · Disease Markers · doi:10.1155/2019/4065327 · Cited by 17
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Background
The Obscure Effect of Tribulus terrestris Saponins Plus Inulin on Liver Morphology, Liver Fatty Acids, Plasma Glucose, and Lipid Profile in SD Rats with and without Induced Type 2 Diabetes Mellitus
Misiakiewicz-Has, K., Maciejewska, D., Rzeszotek, S., Pilutin, A., Kolasa, A., Szumilas, P., Stachowska, E., & Wiszniewska, B. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22168680 · Cited by 16
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Growth dynamics and differential accumulation of picrosides and its precursor metabolites in callus cell lines of Picrorhiza kurroa with distinct anti-steatotic potential
Partap, M., Chhimwal, J., Kumar, P., Kumar, D., Padwad, Y. S., & Warghat, A. R. (2022) · Process Biochemistry · doi:10.1016/j.procbio.2022.06.002 · Cited by 16
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Metabolomics to identify fingerprints of carotid atherosclerosis in nonobese metabolic dysfunction-associated fatty liver disease
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“Increased de novo lipogenesis is a distinct characteristic of individuals with MAFLD [33].”
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Hepatocyte FBXW7-dependent activity of nutrient-sensing nuclear receptors controls systemic energy homeostasis and NASH progression in male mice
Xia, H., Dufour, C. R., Medkour, Y., Scholtes, C., Chen, Y., Guluzian, C., B'Chir, W., & Giguère, V. (2023) · Nature Communications · doi:10.1038/s41467-023-42785-3 · Cited by 17
“In this manuscript authors, attempt to dive deeper into the phenotype, integrating various -omics analysis, analysis of multiple organs and indicate a potential function of nutrient sensing nuclear receptors ERRa and PPARa during the progression to NASH.”
High sucrose intake exacerbates airway inflammation through pathogenic Th2 and Th17 response in ovalbumin (OVA)-induced acute allergic asthma in C57BL/6 mice
Kim, H. J., Dinh, D. T. T., Yang, J., Herath, K. H. I. N. M., Seo, S. H., Son, Y., Kang, I., & Jee, Y. (2023) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2023.109504 · Cited by 16
Lipoprotein Combine Index as a Better Marker for NAFLD Identification Than Traditional Lipid Parameters
Qiu, J., Huang, X., Kuang, M., Yang, R., Li, J., Sheng, G., & Zou, Y. (2024) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s462181 · Cited by 18
Liver metabolism in human MASLD: A review of recent advancements using human tissue metabolomics
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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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