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Increased De Novo Lipogenesis Is a Distinct Characteristic of Individuals With Nonalcoholic Fatty Liver Disease
Open accessAbstract
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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“Postprandial DNL contributes to 15-26% of liver TAGs in individuals with MASLD49,56 vs. 1-6% in the fasting state in healthy individuals.48”
From Lipid metabolism in MASLD and MASH: From mechanism to the clinic (2024) · cites this paper as [49]
Experimental — accuracy not yet measuredIn the citing paper
“Fasting DNL correlated with plasma TAG concentrations48 and was higher in individuals with MASLD.49”
From Lipid metabolism in MASLD and MASH: From mechanism to the clinic (2024) · cites this paper as [49]
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Citations
Cites
Prevalence of Hepatic Steatosis in An Urban Population in the United States: Impact of Ethnicity
Browning, J. D., Szczepaniak, L. S., Dobbins, R., Nuremberg, P., Horton, J. D., Cohen, J. C., Grundy, S. M., & Hobbs, H. H. (2004) · Hepatology · doi:10.1002/hep.20466 · Cited by 3,664
Self-citationDonnelly, K. L., Smith, C. I., Schwarzenberg, S. J., Jessurun, J., Boldt, M. D., & Parks, E. J. (2005) · Journal of Clinical Investigation · doi:10.1172/jci23621 · Cited by 3,604
Self-citationNonalcoholic Fatty Liver Disease
Marchesini, G., Brizi, M., Bianchi, G., Tomassetti, S., Bugianesi, E., Lenzi, M., McCullough, A. J., Natale, S., Forlani, G., & Melchionda, N. (2001) · Diabetes · doi:10.2337/diabetes.50.8.1844 · Cited by 2,581
Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities
Sanyal, A. J., Campbell–Sargent, C., Mirshahi, F., Rizzo, W. B., Contos, M. J., Sterling, R. K., Luketic, V. A., Shiffman, M. L., & Clore, J. N. (2001) · Gastroenterology · doi:10.1053/gast.2001.23256 · Cited by 2,078
Triglyceride accumulation protects against fatty acid-induced lipotoxicity
Listenberger, L. L., Han, X., Lewis, S. E., Cases, S., Farese, R. V., Ory, D. S., & Schaffer, J. E. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0630588100 · Cited by 2,075
Stanhope, K. L., Schwarz, J. M., Keim, N. L., Griffen, S. C., Bremer, A. A., Graham, J. L., Hatcher, B., Cox, C. L., Dyachenko, A., Zhang, W., et al. (2009) · Journal of Clinical Investigation · doi:10.1172/jci37385 · Cited by 1,765
McGarry, J. D. (2002) · Diabetes · doi:10.2337/diabetes.51.1.7 · Cited by 1,435
Charlton, M., Burns, J. M., Pedersen, R. A., Watt, K. D. S., Heimbach, J. K., & Dierkhising, R. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.06.061 · Cited by 1,115
Disordered lipid metabolism and the pathogenesis of insulin resistance.
Savage, D. B., Petersen, K. F., & Shulman, G. I. (2007) · Physiological Reviews · doi:10.1152/physrev.00024.2006 · Cited by 1,107
Shimano, H., Horton, J. D., Hammer, R. E., Shimomura, I., Brown, M. S., & Goldstein, J. L. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118951 · Cited by 817
Cited by
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Items 201–300 of 998
Lau, L. H. S., & Wong, S. H. (2018) · Advances in experimental medicine and biology · doi:10.1007/978-981-10-8684-7_9 · Cited by 93
ATP-citrate lyase: genetics, molecular biology and therapeutic target for dyslipidemia
Burke, A. C., & Huff, M. W. (2017) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000390 · Cited by 91
Barb, D., Kalavalapalli, S., Leiva, E. G., Bril, F., Huot-Marchand, P., Dzen, L., Rosenberg, J. T., Junien, J., Broqua, P., Rocha, A. O., et al. (2025) · Journal of Hepatology · doi:10.1016/j.jhep.2024.12.045 · Cited by 101
Tan, Y., Kim, J., Cheng, J., Ong, M., Lao, W., Jin, X., Lin, Y.-G., Xiao, L., Zhu, X., & Qu, X. (2017) · World Journal of Gastroenterology · doi:10.3748/wjg.v23.i21.3805 · Cited by 91
Clinical assessment of hepatic de novo lipogenesis in non-alcoholic fatty liver disease
Paglialunga, S., & Dehn, C. A. (2016) · Lipids in Health and Disease · doi:10.1186/s12944-016-0321-5 · Cited by 93
“Augmented hepatic DNL rates are now considered a causal factor in the development of NAFLD [5, 20, 27].”
BackgroundmiR-192-5p regulates lipid synthesis in non-alcoholic fatty liver disease through SCD-1
Liu, X., Cao, H., Wang, B., Xin, F., Zhang, R.-N., Zhou, D., Yang, R., Zhao, Z., Pan, Q., & Fan, J. (2017) · World Journal of Gastroenterology · doi:10.3748/wjg.v23.i46.8140 · Cited by 90
Hepatic ketogenic insufficiency reprograms hepatic glycogen metabolism and the lipidome
d’Avignon, D. A., Puchalska, P., Erçal, B., Chang, Y., Martin, S. E., Graham, M. J., Patti, G. J., Han, X., & Crawford, P. A. (2018) · JCI Insight · doi:10.1172/jci.insight.99762 · Cited by 89
Hepatic Insulin Resistance Is Not Pathway Selective in Humans With Nonalcoholic Fatty Liver Disease
ter Horst, K. W., Vatner, D. F., Zhang, D., Cline, G. W., Ackermans, M. T., Nederveen, A. J., Verheij, J., Demirkiran, A., van Wagensveld, B. A., Dallinga-Thie, G. M., et al. (2021) · Diabetes Care · doi:10.2337/dc20-1644 · Cited by 88
Orlicky, D. J., Libby, A. E., Bales, E. S., McMahan, R. H., Monks, J., Rosa, F. G. L., & McManaman, J. L. (2018) · The Journal of Physiology · doi:10.1113/jp277140 · Cited by 88
“Thus, additional studies of the effects of hepatic Plin2 expression on the levels and activities of hepatic DNL enzymes and lipid flux (Lambert et al. 2014) will be needed to precisely establish the functional importance of Plin2 in regulating the effects of obesity on DNL and fatty acid uptake,…”
BackgroundPathogenesis of Insulin Resistance and Atherogenic Dyslipidemia in Nonalcoholic Fatty Liver Disease
Akhtar, D. H., Iqbal, U., Vazquez‐Montesino, L. M., Dennis, B. B., & Ahmed, A. (2019) · Journal of Clinical and Translational Hepatology · doi:10.14218/jcth.2019.00028 · Cited by 89
“Fructose is exclusively metabolized by the liver and thus, is converted into triglycerides via DNL.”
BackgroundWhy Do So Many Nonalcoholic Steatohepatitis Trials Fail?
Ratziu, V., & Friedman, S. L. (2023) · Gastroenterology · doi:10.1053/j.gastro.2020.05.046 · Cited by 88
Nikolaou, N., Gathercole, L., Marchand, L., Althari, S., Dempster, N. J., Green, C., van de Bunt, M., McNeil, C. A., Arvaniti, A., Hughes, B. A., et al. (2019) · Metabolism · doi:10.1016/j.metabol.2019.153947 · Cited by 86
“Fatty acid delivery from adipose tissue lipolysis, arising as a consequence of adipose tissue insulin resistance, remains the predominant source of TAG within hepatocytes, however, TAG synthesis via DNL increases in importance with NAFLD severity [34,35].”
BackgroundCohen, C. C., Li, K. W., Alazraki, A. L., Beysen, C., Carrier, C., Cleeton, R. L., Dandan, M., Figueroa, J., Knight‐Scott, J., Knott, C. J., et al. (2021) · Journal of Clinical Investigation · doi:10.1172/jci150996 · Cited by 86
“Specifically, hepatic DNL was measured using a 7-day labeling protocol, which more accurately assesses the contribution of DNL to the slowly turning over storage pool of TG in the liver (11, 12, 24).”
BackgroundMethodZhang, M., Chi, X., Qu, N., & Wang, C. (2018) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2018.03.127 · Cited by 85
Zheng, Z., Zhang, X., Liu, X.-X., Jin, X., Dai, L., Cheng, H., Jing, D., Thu, P. M., Zhang, M., Li, H., et al. (2019) · Theranostics · doi:10.7150/thno.36505 · Cited by 85
“Notably, in patients with non-alcoholic fatty liver disease (NAFLD), triglyceride turnover rates were not increased [13], while DNL accounts more than 20% of liver TG, 3-5 times higher than healthy populations [14, 15].”
BackgroundGreen, C., Pramfalk, C., Charlton, C. A., Gunn, P. J., Cornfield, T., Pavlides, M., Karpe, F., & Hodson, L. (2020) · BMJ Open Diabetes Research & Care · doi:10.1136/bmjdrc-2019-000871 · Cited by 85
Fernandes‐da‐Silva, A., Miranda, C. S., Santana-Oliveira, D. A., Oliveira-Cordeiro, B., Rangel-Azevedo, C., Silva-Veiga, F. M., Martins, F. F., & Souza‐Mello, V. (2021) · European Journal of Nutrition · doi:10.1007/s00394-021-02542-y · Cited by 86
Beyond the X Factor: Relevance of Sex Hormones in NAFLD Pathophysiology
Torre, S. D. (2021) · Cells · doi:10.3390/cells10092502 · Cited by 91
Vetrano, E., Rinaldi, L., Mormone, A., Giorgione, C., Galiero, R., Caturano, A., Nevola, R., Marfella, R., & Sasso, F. C. (2023) · Biomedicines · doi:10.3390/biomedicines11020468 · Cited by 94
“This pathway is an important contributor to hepatic lipid accumulation in the pathogenesis of NAFLD [28,29].”
BackgroundRao, G., Peng, X., Li, X., An, K., He, H., Fu, X., Li, S., & An, Z. (2023) · Frontiers in Medicine · doi:10.3389/fmed.2023.1294267 · Cited by 93
Navarro, L. A., Wree, A., Povero, D., Berk, M. P., Eguchi, A., Ghosh, S., Papouchado, B. G., ERZURUM, S. C., & Feldstein, A. E. (2014) · Journal of Hepatology · doi:10.1016/j.jhep.2014.09.015 · Cited by 84
“Indeed, an increase in DNL is found in different experimental models of NAFLD as well as in patients with NAFLD [38].”
Hydes, T., Ravi, S., Loomba, R. S., & Gray, M. E. (2020) · Clinical and Molecular Hepatology · doi:10.3350/cmh.2020.0067 · Cited by 90
“The secretion of adipokines (adiponectin, resistin, leptin, visfatin) and pro-inflammatory cytokines (interleukins and tissue necrosis factor α) from VAT induce a state of systemic low-grade chronic inflammation which can promote the onset of NAFLD and NASH.18-20 Randomized controlled trial data The findings from key…”
BackgroundInfluentialKord‐Varkaneh, H., Salehi‐Sahlabadi, A., Tinsley, G. M., Santos, H. O., & Hekmatdoost, A. (2022) · Nutrition · doi:10.1016/j.nut.2022.111847 · Cited by 89
Williams, K. J., & Wu, X. (2016) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2016.02.004 · Cited by 83
“Note that overactive de-novo lipogenesis in the liver can be harmful (red in Figure 3A), by promoting non-alcoholic fatty liver disease and oversecretion of large VLDL1, a key C-TRL in metabolic dyslipoproteinemia [135, 137, 140, 210, 276, 277, 419-421].”
BackgroundInfluentialIntestinal TGR5 agonism improves hepatic steatosis and insulin sensitivity in Western diet-fed mice
Finn, P. D., Rodriguez, D. J., Kohler, J. N., Jiang, Z., Wan, S., Blanco, E. J., King, A. J., Chen, T., Bell, N., Dragoli, D. R., et al. (2019) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00300.2018 · Cited by 82
“However, their use has until now been associated with undesirable side effects, such as excessive gallbladder filling and blockade of gallbladder emptying, caused by systemic TGR5 agonism in off-target tissues (5, 8, 14, 20, 23, 25).”
BackgroundTruong, X. T., & Lee, D. H. (2025) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2025.0644 · Cited by 84
“Patients with MASLD show a marked increase in hepatic DNL and elevated nocturnal plasma FFA levels [60,69,70].”
InfluentialIsorhamnetin Alleviates Steatosis and Fibrosis in Mice with Nonalcoholic Steatohepatitis
Ganbold, M., Owada, Y., Ozawa, Y., Shimamoto, Y., Ferdousi, F., Tominaga, K., Zheng, Y., Ohkohchi, N., & Isoda, H. (2019) · Scientific Reports · doi:10.1038/s41598-019-52736-y · Cited by 81
Dysregulated Lipid Metabolism Precedes Onset of Psychosis
Dickens, A. M., Sen, P., Kempton, M. J., Barrantes‐Vidal, N., Iyegbe, C. O., Nordentoft, M., Pollak, T. A., Riecher‐Rössler, A., Ruhrmann, S., Sachs, G., et al. (2020) · Biological Psychiatry · doi:10.1016/j.biopsych.2020.07.012 · Cited by 79
Berardo, C., Pasqua, L. G. D., Cagna, M., Richelmi, P., Vairetti, M., & Ferrigno, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21249646 · Cited by 89
“Several studies have demonstrated that an elevated rate of hepatic DNL is a characteristic feature of NAFLD both in animal models and in patients [73,74].”
BackgroundSmith, B. K., Ford, R. J., Desjardins, E. M., Green, A. E., Hughes, M. C., Houde, V. P., Day, E. A., Marcinko, K., Crane, J. D., Mottillo, E. P., et al. (2016) · Diabetes · doi:10.2337/db16-0564 · Cited by 79
“NAFLD is associated with increased rates of hepatic DNL (43,44), and this report is the first to show that DNL can be suppressed in vivo with an acute, therapeutically relevant dose of salsalate.”
BackgroundDagorn, P. G., Foretz, M., Steinberg, G. R., Batchuluun, B., Zawistowska‐Deniziak, A., Lambooij, J. M., Guigas, B., Carling, D., Monternier, P., Moller, D. E., et al. (2021) · Hepatology Communications · doi:10.1002/hep4.1799 · Cited by 78
Mancina, R. M., Matikainen, N., Maglio, C., Söderlund, S., Lundbom, N. M. I., Hakkarainen, A., Rametta, R., Mozzi, E., Fargion, S. R., Valenti, L. V. C., et al. (2015) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-4464 · Cited by 77
“It has recently been reported that DNL was 3-fold higher in subjects with NAFLD, suggesting DNL was the key feature associated with fatty liver (4).”
BackgroundIvashkin, V. T., Maevskaya, M. V., Жаркова, М. С., Kotovskaya, Y. V., Ткачева, О. Н., Troshina, E. A., Shestakova, M. V., Maev, I. V., Breder, V. V., Geyvandova, N. I., et al. (2022) · Russian Journal of Gastroenterology Hepatology Coloproctology · doi:10.22416/1382-4376-2022-32-4-104-140 · Cited by 86
Physiological Suppression of Lipotoxic Liver Damage by Complementary Actions of HDAC3 and SCAP/SREBP
Papazyan, R., Sun, Z., Kim, Y. H., Titchenell, P. M., Hill, D. A., Lu, W., Damle, M., Wan, M., Zhang, Y., Briggs, E. R., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.10.012 · Cited by 80
“Furthermore, in addition to lipogenesis, abnormal fatty acid uptake, oxidation, and secretion can also contribute to fatty liver formation (Donnelly et al., 2005; Lambert et al., 2014; Sunny et al., 2011).”
BackgroundA comprehensive review on high -fat diet-induced diabetes mellitus: an epigenetic view
Prasad, M., Rajagopal, P., Devarajan, N., Veeraraghavan, V. P., Palanisamy, C. P., Cui, B., Patil, S., & Jayaraman, S. (2022) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2022.109037 · Cited by 83
Rosso, C., Mezzabotta, L., Gaggini, M., Salomone, F., Gambino, R., Marengo, A., Saba, F., Vanni, E., Younes, R., Saponaro, C., et al. (2015) · Hepatology · doi:10.1002/hep.28287 · Cited by 76
High glycemic index metabolic damage – a pivotal role of GIP and GLP-1
Pfeiffer, A. F. H., & Keyhani-Nejad, F. (2018) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2018.03.003 · Cited by 74
“Increased de novo lipogenesis from sugars contributes to hepatic fat content and is elevated in patients with hepatic steatosis [31,32].”
Hepatic glycogenesis antagonizes lipogenesis by blocking S1P via UDPG
Chen, J., Zhou, Y., Liu, Z., Lu, Y. H., Jiang, Y., Cao, K., Zhou, N., Wang, D., Zhang, C., Zhou, N., et al. (2024) · Science · doi:10.1126/science.adi3332 · Cited by 78
“Our findings are consistent with the notion of increased lipogenesis as a distinct characteristic of NAFLD ( 51 ).”
ResultGunn, P. J., Green, C., Pramfalk, C., & Hodson, L. (2017) · Physiological Reports · doi:10.14814/phy2.13532 · Cited by 74
“…of TAG can result from elevated delivery or synthesis of fatty acids (FAs), reduced secretion or oxidation of FAs, or both: several of these processes have been shown to be perturbed in individuals with NAFLD (Diraison et al. 2003; Fabbrini et al. 2008; Lambert et al. 2014; Green et al. 2015b).”
BackgroundResultHo, C., Gao, Y., Zheng, D., Liu, Y., Shan, S., Fang, B., Zhao, Y., Song, D., Zhang, Y., & Li, Q. (2019) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.14380 · Cited by 73
Beyond Body Weight-Loss: Dietary Strategies Targeting Intrahepatic Fat in NAFLD
Worm, N. (2020) · Nutrients · doi:10.3390/nu12051316 · Cited by 78
Rational combination therapy for NASH: Insights from clinical trials and error
Ratziu, V., & Charlton, M. (2023) · Journal of Hepatology · doi:10.1016/j.jhep.2022.12.025 · Cited by 71
Dong, Y., Lv, Q., Li, S., Wu, Y., Li, L., Li, J., Zhang, F., Sun, X., & Tong, N. (2017) · Clinics and Research in Hepatology and Gastroenterology · doi:10.1016/j.clinre.2016.11.009 · Cited by 71
Fructose drives de novo lipogenesis affecting metabolic health
Geidl, B., & Gerber, P. A. (2023) · Journal of Endocrinology · doi:10.1530/joe-22-0270 · Cited by 84
Lambert, J. E., Parnell, J. A., Eksteen, B., Raman, M., Bomhof, M. R., Rioux, K. P., Madsen, K. L., & Reimer, R. A. (2015) · BMC Gastroenterology · doi:10.1186/s12876-015-0400-5 · Cited by 73
“Plasma will be ultracentrifugated to isolate total TG-rich lipoproteins, which at fasting will be primarily VLDL arising from the liver [12, 108].”
BackgroundMethodSelf-citationDietary carbohydrates and fatty liver disease
Chiu, S., Mulligan, K. M., & Schwarz, J. (2018) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0000000000000469 · Cited by 72
Kupriyanova, Y., Zaharia, O., Bobrov, P., Karusheva, Y., Burkart, V., Szendroedi, J., Hwang, J., Roden, M., Roden, M., Al‐Hasani, H., et al. (2020) · Journal of Hepatology · doi:10.1016/j.jhep.2020.11.030 · Cited by 75
Dual-5α-Reductase Inhibition Promotes Hepatic Lipid Accumulation in Man
Hazlehurst, J., Oprescu, A. I., Nikolaou, N., Guida, R. D., Grinbergs, A., Davies, N. P., Flintham, R., Armstrong, M. J., TAYLOR, A. E. R., Hughes, B. A., et al. (2015) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-2928 · Cited by 71
Quantitative flux analysis in mammals
Bartman, C., TeSlaa, T. A., & Rabinowitz, J. D. (2021) · Nature Metabolism · doi:10.1038/s42255-021-00419-2 · Cited by 73
Cree‐Green, M., Bergman, B. C., Coe, G. V., Newnes, L., Baumgartner, A., Bacon, S. D., Scherzinger, A. L., Pyle, L. L., & Nadeau, K. J. (2016) · Obesity · doi:10.1002/oby.21651 · Cited by 70
“Limited studies in adults with NAFLD have indicated that upregulated lipogenesis and FFA delivery are the primary contributors to HS (16,28).”
BackgroundInfluentialThe immune landscape in nonalcoholic steatohepatitis
Narayanan, S., Surette, F. A., & Hahn, Y. S. (2016) · Immune Network · doi:10.4110/in.2016.16.3.147 · Cited by 64
“Hepatic steatosis is further exacerbated by the upregulation of de novo lipogenesis, which occurs despite a parallel rise in insulin resistance (2).”
BackgroundOne-Carbon Metabolism in Fatty Liver Disease and Fibrosis: One-Carbon to Rule Them All
da Silva, R. P., Eudy, B. J., & Rafael, D. (2020) · Journal of Nutrition · doi:10.1093/jn/nxaa032 · Cited by 70
Gerges, S. H., Wahdan, S. A., Elsherbiny, D. A., & El‐Demerdash, E. (2021) · Life Sciences · doi:10.1016/j.lfs.2021.119220 · Cited by 76
Polysaccharides influence human health via microbiota-dependent and -independent pathways
Gan, L., Wang, J., & Guo, Y. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2022.1030063 · Cited by 77
Fatty acids in non-alcoholic steatohepatitis: Focus on pentadecanoic acid
Yoo, W., Gjuka, D., Stevenson, H. L., Song, X., Shen, H., Yoo, S. Y., Wang, J., Fallon, M. B., Ioannou, G. N., Harrison, S. A., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0189965 · Cited by 69
von Loeffelholz, C., Coldewey, S. M., & Birkenfeld, A. L. (2021) · Cells · doi:10.3390/cells10071822 · Cited by 70
Li, N., Yin, L., Shang, J., Liang, M., Liu, Z., Yang, H., Qiang, G., Du, G., & Yang, X. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115113 · Cited by 71
Regulation of hepatic lipogenesis by the zinc finger protein Zbtb20
Liu, G., Zhou, L., Zhang, H., Chen, R., Zhang, Y., Li, L., Lu, J.-Y., Jiang, H., Liu, D., Qi, S., et al. (2017) · Nature Communications · doi:10.1038/ncomms14824 · Cited by 68
Bempedoic acid: effects on lipoprotein metabolism and atherosclerosis
Burke, A. C., Telford, D. E., & Huff, M. W. (2018) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000565 · Cited by 67
Xiao, M., Lin, J.-S., Li, Y., Liu, M., Deng, Y., Wang, C., & Chen, Y. (2019) · Public Health Nutrition · doi:10.1017/s1368980019002568 · Cited by 67
“Excess glucose, fructose and amino acids are converted to TAG in the liver via de novo lipogenesis, which increases in NAFLD(32).”
BackgroundBergman, A. J., Carvajal‐Gonzalez, S., Tarabar, S., Saxena, A. R., Esler, W. P., & Amin, N. B. (2020) · Clinical Pharmacology in Drug Development · doi:10.1002/cpdd.782 · Cited by 68
Zhao, X., Xiaoli, Zong, H., Abdulla, A., Yang, E. S. T., Wang, Q., Ji, J., Pessin, J. E., Das, B. C., & Yang, F. (2014) · Diabetes · doi:10.2337/db13-0835 · Cited by 69
“Although fatty acids from diets and adipose tissue lipolysis support reesterification in the liver to drive triglyceride synthesis, up to 30% of hepatic fatty acids are from de novo lipogenesis in NAFLD, but less than 5% in normal individuals (5; 6).”
BackgroundInsulin Regulates Hepatic Triglyceride Secretion and Lipid Content via Signaling in the Brain
Scherer, T., Lindtner, C., O’Hare, J., Hackl, M. T., Zieliński, E., Freudenthaler, A., Baumgartner-Parzer, S. M., Tödter, K., Heeren, J., Krššák, M., et al. (2016) · Diabetes · doi:10.2337/db15-1552 · Cited by 72
“Increased hepatic triglyceride (TG) synthesis can be the result of 1) increased de novo lipogenesis in the liver (2), 2) increased delivery of fatty acid (FA) to the liver due to excessive dietary lipid intake and/or unrestrained lipolysis in white adipose tissue (WAT) (3), and 3) decreased hepatic lipid oxidation (4).”
BackgroundMetabolic subtypes of patients with NAFLD exhibit distinctive cardiovascular risk profiles
Martínez‐Arranz, I., Bruzzone, C., Noureddin, M., Gil‐Redondo, R., Mincholé, I., Bizkarguenaga, M., Arretxe, E., Iruarrizaga‐Lejarreta, M., Fernández‐Ramos, D., Lopitz‐Otsoa, F., et al. (2022) · Hepatology · doi:10.1002/hep.32427 · Cited by 65
Brg1 regulates pro-lipogenic transcription by modulating SREBP activity in hepatocytes
Li, N., Li, M., Hong, W., Shao, J., Xu, H., Shimano, H., Lu, J. L., & Xu, Y. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2018.05.022 · Cited by 65
Significance of Simple Steatosis: An Update on the Clinical and Molecular Evidence
Mazzolini, G. D., Sowa, J., Atorrasagasti, C., Kücükoglu, Ö., Syn, W., & Canbay, A. E. (2020) · Cells · doi:10.3390/cells9112458 · Cited by 65
“Patients with high liver fat content exhibit at least threefold higher levels of DNL when compared with individuals with low liver fat content despite similar levels of FFA flux from the adipose tissue; therefore, DNL is a major contributor to the development of steatosis, apart from lipolysis [65].”
BackgroundTriglycerides in Nonalcoholic Fatty Liver Disease: Guilty Until Proven Innocent
Semova, I., & Biddinger, S. B. (2021) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2020.12.001 · Cited by 69
Treviño, S., Velázquez-Vázquez, D., Sánchez‐Lara, E., Díaz, A., Flores-Hernández, J. Á., Pérez-Benı́tez, A., Brambila, E., & Vergara, E. G. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/6058705 · Cited by 65
“It is important to emphasize that insulin signaling is associated with hepatic lipogenesis and mobility of triglycerides into VLDL; therefore, low levels of the hormone in DM1 early models produce lower levels of serum triglycerides, although these are accumulated in liver, as shown Table 1 [28–30].”
BackgroundCyclophilin D deficiency attenuates mitochondrial perturbation and ameliorates hepatic steatosis
Wang, X., Du, H., Shao, S., Bo, T., Yu, C., Chen, W., Zhao, L., Li, Q., Wang, L., Liu, X., et al. (2018) · Hepatology · doi:10.1002/hep.29788 · Cited by 66
“In all of the hypothesis, fat accumulation in the liver (steatosis) is thought to be the early stage of NAFLD (5) and may process to end stage liver disease (6).”
Sex-based differences in hepatic and skeletal muscle triglyceride storage and metabolism
Beaudry, K. M., & Devries, M. C. (2019) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/apnm-2018-0635 · Cited by 69
“Increased rates of DNL are hypothesized to be involved in Page 12 of 39 https://mc06.manuscriptcentral.com/apnm-pubs Applied Physiology, Nutrition, and Metabolism Draft 13 the development of NAFLD (Lambert et al. 2014) with a greater amount of DNL-produced TGs being incorporated into VLDLs (15”
BackgroundDysregulation of hepatic metabolism with obesity: factors influencing glucose and lipid metabolism
Nagarajan, S. R., Cross, E., Sanna, F., & Hodson, L. (2021) · Proceedings of The Nutrition Society · doi:10.1017/s0029665121003761 · Cited by 68
“In support of this hypothesis, studies by Lambert et al.((46)) and Smith et al.”
InfluentialTargeting mitochondria to oppose the progression of nonalcoholic fatty liver disease
Grattagliano, I., Montezinho, L. P., Oliveira, P. J., Frühbeck, G., Gómez‐Ambrosi, J., Montecucco, F., Carbone, F., Wieckowski, M. R., Wang, D. Q. ‐., & Portincasa, P. (2018) · Biochemical Pharmacology · doi:10.1016/j.bcp.2018.11.020 · Cited by 66
“binding protein (ChREBP) and sterol regulatory element-binding protein 1 (SREBP1) which will further increase intrahepatic lipid supply by about 25% [37,38].”
BackgroundThe mitochondrial pyruvate carrier at the crossroads of intermediary metabolism
Yiew, N. K. H., & Finck, B. N. (2022) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00074.2022 · Cited by 64
Steatosis and NASH in type 2 diabetes
Hu, M., Phan, F., Bourron, O., Ferré, P., & Foufelle, F. (2017) · Biochimie · doi:10.1016/j.biochi.2017.10.019 · Cited by 65
Tumor suppressor ZHX2 inhibits NAFLD–HCC progression via blocking LPL-mediated lipid uptake
Wu, Z., Ma, H., Wang, L., Song, X., Zhang, J., Liu, W., Ge, Y., Sun, Y., Yu, X., Wang, Z., et al. (2019) · Cell Death and Differentiation · doi:10.1038/s41418-019-0453-z · Cited by 63
Liver Pyruvate Kinase Promotes NAFLD/NASH in Both Mice and Humans in a Sex-Specific Manner
Krishnan, K. C., Floyd, R. R., Sabir, S., Jayasekera, D. W., León‐Mimila, P., Jones, A. E., Cortez, A. A., Shravah, V., Péterfy, M., Stiles, L., et al. (2020) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2020.09.004 · Cited by 62
Reyes-Caballero, H., Rao, X., Sun, Q., Warmoes, M. O., Lin, P., Sussan, T. E., Park, B., Fan, T. W. ‐., Maiseyeu, A., Rajagopalan, S., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-53716-y · Cited by 64
Chen, Y., Chiu, C.-C., Hung, S., Huang, W.-C., Lee, Y.-P., Liu, J.-Y., Huang, Y.-T., Chen, T.-H., & Chuang, H.-L. (2019) · Nutrition Research · doi:10.1016/j.nutres.2019.07.001 · Cited by 60
Ju, U.-I., Jeong, D., Seo, J., Park, J. B., Park, J., Suh, K., Kim, J. B., & Chun, Y. (2020) · Cell Death and Disease · doi:10.1038/s41419-020-2472-6 · Cited by 60
Beals, J. W., Smith, G. I., Shankaran, M., Fuchs, A. G., Schweitzer, G. G., Yoshino, J., Field, T., Matthews, M. D., Nyangau, E., Morozov, D., et al. (2021) · Hepatology · doi:10.1002/hep.31822 · Cited by 64
Tsilingiris, D., Tzeravini, E., Koliaki, C. C., Dalamaga, Μ., & Kokkinos, A. D. (2021) · Current Obesity Reports · doi:10.1007/s13679-021-00434-0 · Cited by 60
“Furthermore, the increased ATP production may facilitate the unwanted effect of its utilization in aberrantly activated energy-demanding procedures such as de novo lipogenesis [153] or gluconeogenesis [121, 131], despite increased insulin levels.”
BackgroundBae, U., Park, J., Park, I. W., Chae, B. M., Oh, M., Jung, S., Ryu, G.-S., Chae, S., & Park, B. (2018) · The American Journal of Chinese Medicine · doi:10.1142/s0192415x18500325 · Cited by 61
Parafati, M., Kirby, R. J., Khorasanizadeh, S., Rastinejad, F., & Malany, S. (2018) · Disease Models & Mechanisms · doi:10.1242/dmm.033530 · Cited by 64
“Studies in humans revealed the importance of de novo lipogenesis in the excessive hepatic accumulation of TAG, contributing to about a quarter of liver lipids in patients affected by NAFLD (Donnelly et al., 2005; Lambert et al., 2014).”
Lee, Y., Hu, S., Park, Y., & Lee, J. (2019) · Preventive Nutrition and Food Science · doi:10.3746/pnf.2019.24.2.103 · Cited by 62
“Obese subjects with liver steatosis have ∼3-fold higher rates of de novo lipogenesis than those without liver steatosis (Lambert et al., 2014).”
BackgroundHepatocyte Injury and Hepatic Stem Cell Niche in the Progression of Non-Alcoholic Steatohepatitis
Overi, D., Carpino, G., Franchitto, A., Onori, P., & Gaudio, E. (2020) · Cells · doi:10.3390/cells9030590 · Cited by 62
“Insulin resistance has a prominent role in these processes by favoring an increased lipolytic response to the meal, and by inducing the expression of lipogenic pathways in the liver [24,25,27,31,32].”
BackgroundGuerra, S., Mocciaro, G., & Gastaldelli, A. (2021) · European Journal of Clinical Investigation · doi:10.1111/eci.13695 · Cited by 61
Maevskaya, M. V., Kotovskaya, Y. V., Ivashkin, V. T., Ткачева, О. Н., Troshina, E. A., Shestakova, M. V., Breder, V. V., Geyvandova, N. I., Doshchitsin, V. L., Dudinskaya, Е. N., et al. (2022) · Terapevticheskii arkhiv · doi:10.26442/00403660.2022.02.201363 · Cited by 66
Nonalcoholic Fatty Liver Disease and Omega-3 Fatty Acids: Mechanisms and Clinical Use
Spooner, M. H., & Jump, D. Β. (2023) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-061021-030223 · Cited by 63
“NAFLD patients with increased hepatic palmitoleic acid (C16:1, ω 7) and cis-vaccenic acid (18:1, ω 7) reflect the involvement of Scd1 and Elovl5 in MUFA synthesis (59, 72, 76).”
Mitochondria‐Mediated Pathogenesis and Therapeutics for Non‐Alcoholic Fatty Liver Disease
Li, Z., Li, Y., Zhang, H., Guo, J., Lam, C. W. K., Wang, C., & Zhang, W. (2019) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201900043 · Cited by 64
El-Derany, M. O., & AbdelHamid, S. G. (2021) · Biochemical Pharmacology · doi:10.1016/j.bcp.2021.114624 · Cited by 64
Adaptive and maladaptive roles for ChREBP in the liver and pancreatic islets
Katz, L. S., Baumel-Alterzon, S., Scott, D. K., & Herman, M. A. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.100623 · Cited by 60
The Biological Clock: A Pivotal Hub in Non-alcoholic Fatty Liver Disease Pathogenesis
Mazzoccoli, G., Cosmo, S. D., & Mazza, T. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.00193 · Cited by 62
“…de novo lipogenesis, driven by hyperinsulinemia and unwarranted carbohydrate intake causing triglycerides overload, may not be balanced by adequate increases in very low density lipoprotein (VLDL) secretion and changes in levels of β-oxidation (Lambert et al., 2014; Titchenell et al., 2017).”
BackgroundNi, W., Lin, S., Bian, S., Zheng, W., Qu, L., Fan, Y., Lu, C., Xiao, M., & Zhou, P. (2020) · Cell Death and Disease · doi:10.1038/s41419-020-03075-8 · Cited by 59
Zhang, C., Teng, Y., Li, F., Ho, W., Bai, X., Xu, X., & Zhang, X. (2023) · ACS Nano · doi:10.1021/acsnano.3c03217 · Cited by 63
The role of hepatic lipid composition in obesity‐related metabolic disease
Willis, S. A., Bawden, S., Malaikah, S., Sargeant, J. A., Stensel, D. J., Aithal, G. P., & King, J. A. (2021) · Liver International · doi:10.1111/liv.15059 · Cited by 63
Amin, N. B., Darekar, A., Anstee, Q. M., Wong, V. W., Tacke, F., Vourvahis, M., Lee, D. S., Charlton, M., Alkhouri, N., Nakajima, A., et al. (2022) · BMJ Open · doi:10.1136/bmjopen-2021-056159 · Cited by 57
Reprogramming of Hepatic Metabolism and Microenvironment in Nonalcoholic Steatohepatitis
Rui, L., & Lin, J. D. (2022) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-062220-105200 · Cited by 59
Tian, S., Lei, Y., Zhao, F., Che, J., Wu, Y.-H., Lei, P., Kang, Y. E., & Shan, Y. (2024) · Food & Function · doi:10.1039/d4fo01059k · Cited by 60
Insulin/Snail1 axis ameliorates fatty liver disease by epigenetically suppressing lipogenesis
Liu, Y., Jiang, L., Sun, C., IRELAND, N. M., Shah, Y. M., Liu, Y., & Rui, L. (2018) · Nature Communications · doi:10.1038/s41467-018-05309-y · Cited by 57
Hepatic fat as clinical outcome and therapeutic target for nonalcoholic fatty liver disease
Pelusi, S., & Valenti, L. V. C. (2018) · Liver International · doi:10.1111/liv.13972 · Cited by 59
Metadata
- 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)
- 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
- 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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