The DOI matches its Crossref record; 50 of the 51 references it cites were found in a registry or an index.
Dietary fructose feeds hepatic lipogenesis via microbiota-derived acetate
Open accessAbstract
Consumption of fructose has risen markedly in recent decades owing to the use of sucrose and high-fructose corn syrup in beverages and processed foods 1, and this has contributed to increasing rates of obesity and non-alcoholic fatty liver disease 2-4. Fructose intake triggers de novo lipogenesis in the liver 4-6, in which carbon precursors of acetyl-CoA are converted into fatty acids. The ATP citrate lyase (ACLY) enzyme cleaves cytosolic citrate to generate acetyl-CoA, and is upregulated after consumption of carbohydrates 7. Clinical trials are currently pursuing the inhibition of ACLY as a treatment for metabolic diseases 8. However, the route from dietary fructose to hepatic acetyl-CoA and lipids remains unknown. Here, using in vivo isotope tracing, we show that liver-specific deletion of Acly in mice is unable to suppress fructose-induced lipogenesis. Dietary fructose is converted to acetate by the gut microbiota 9, and this supplies lipogenic acetyl-CoA independently of ACLY 10. Depletion of the microbiota or silencing of hepatic ACSS2, which generates acetyl-CoA from acetate, potently suppresses the conversion of bolus fructose into hepatic acetyl-CoA and fatty acids. When fructose is consumed more gradually to facilitate its absorption in the small intestine, both citrate cleavage in hepatocytes and microorganism-derived acetate contribute to lipogenesis. By contrast, the lipogenic transcriptional program is activated in response to fructose in a manner that is independent of acetyl-CoA metabolism. These data reveal a two-pronged mechanism that regulates hepatic lipogenesis, in which fructolysis within hepatocytes provides a signal to promote the expression of lipogenic genes, and the generation of microbial acetate feeds lipogenic pools of acetyl-CoA.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“an animal study found that dietary fructose could be converted to microbial acetate by the gut microbiota, which may enhance hepatic lipogenesis by supplying lipogenic acetyl-CoA independently of ATP citrate lyase.96”
From Dietary sugar consumption and health: umbrella review (2023) · cites this paper as [96]
The cited source says what the claim attributes to it.
In the citing paper
“In mice, dietary fructose is metabolized by gut microbes into acetate, serving as a source of acetyl-CoA for lipid synthesis [61].”
From The Gut–Brain–Microbiota Connection and Its Role in Autism Spectrum Disorders (2025) · cites this paper as [61]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
MetaboAnalyst 4.0: towards more transparent and integrative metabolomics analysis
Chong, J., Soufan, O., Li, C., Caraus, I., Li, S., Bourque, G., Wishart, D. S., & Xia, J. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky310 · Cited by 3,637
Donnelly, 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
Consumption of high-fructose corn syrup in beverages may play a role in the epidemic of obesity
Bray, G. A., Nielsen, S. J., & Popkin, B. M. (2004) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/79.4.537 · Cited by 1,990
Nadkarni, M. A., Martin, F. E., Jacques, N. A., & Hunter, N. (2002) · Microbiology · doi:10.1099/00221287-148-1-257 · Cited by 1,931
Postic, C., Shiota, M., Niswender, K. D., Jetton, T. L., Chen, Y., Moates, J. M., Shelton, K. D., Lindner, J., Cherrington, A. D., & Magnuson, M. A. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.1.305 · Cited by 1,302
Lambert, J. E., Ramos–Roman, M. A., Browning, J. D., & Parks, E. J. (2014) · Gastroenterology · doi:10.1053/j.gastro.2013.11.049 · Cited by 1,069
Donohoe, D. R., Collins, L. B., Wali, A., Bigler, R., Sun, W., & Bultman, S. J. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.08.033 · Cited by 993
Fructose and sugar: A major mediator of non-alcoholic fatty liver disease
Jensen, T., Abdelmalek, M. F., Sullivan, S. A., Nadeau, K. J., Cree‐Green, M., Roncal, C., Nakagawa, T., Kuwabara, M., Sato, Y., Kang, D., et al. (2018) · Journal of Hepatology · doi:10.1016/j.jhep.2018.01.019 · Cited by 993
Role of Dietary Fructose and Hepatic De Novo Lipogenesis in Fatty Liver Disease
Softic, S., Cohen, D. E., & Kahn, C. R. (2016) · Digestive Diseases and Sciences · doi:10.1007/s10620-016-4054-0 · Cited by 709
The Small Intestine Converts Dietary Fructose into Glucose and Organic Acids
Jang, C., Hui, S., Lu, W., Cowan, A. J., Morscher, R. J., Lee, G., Liu, W., Tesz, G. J., Birnbaum, M. J., & Rabinowitz, J. D. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2017.12.016 · Cited by 639
Self-citation
Cited by
Sorted by citations
Inflammation in obesity, diabetes, and related disorders
Rohm, T. V., Meier, D. T., Olefsky, J. M., & Donath, M. Y. (2022) · Immunity · doi:10.1016/j.immuni.2021.12.013 · Cited by 2,066
Bian, X., Liu, R. R., Meng, Y., Xing, D., Xu, D., & Lu, Z. (2020) · The Journal of Experimental Medicine · doi:10.1084/jem.20201606 · Cited by 1,037
Modulation of cellular processes by histone and non-histone protein acetylation
Shvedunova, M., & Akhtar, A. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00441-y · Cited by 1,007
Gut-liver axis: Pathophysiological concepts and clinical implications
Tilg, H., Adolph, T. E., & Trauner, M. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.09.017 · Cited by 843
Metabolic reprogramming and epigenetic modifications on the path to cancer
Sun, L., Zhang, H., & Gao, P. (2021) · Protein & Cell · doi:10.1007/s13238-021-00846-7 · Cited by 818
“…bodies (Xia et al., 2017; Hopkins et al., 2018), choline (Romano et al., 2017), arginine (PoilletPerez et al., 2018), glutamine (Ishak Gabra et al., 2020), fructose (Goncalves et al., 2019; Zhao et al., 2020), or cysteine (Badgley et al., 2020) mediates the progression of multiple types of cancer.”
BackgroundLipid metabolism in cancer: New perspectives and emerging mechanisms
Broadfield, L. A., Pane, A. A., Talebi, A., Swinnen, J. V., & Fendt, S. (2021) · Developmental Cell · doi:10.1016/j.devcel.2021.04.013 · Cited by 793
Short-chain fatty acids in diseases
Zhang, D., Jian, Y., Zhang, Y., Li, Y., Gu, L.-T., Sun, H.-H., Liu, M., Zhou, H., Wang, Y., & Xu, Z. (2023) · Cell Communication and Signaling · doi:10.1186/s12964-023-01219-9 · Cited by 813
A Global View of the Interplay between Non-Alcoholic Fatty Liver Disease and Diabetes
Stefan, N., & Cusi, K. (2022) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(22)00003-1 · Cited by 593
Gut–liver axis: barriers and functional circuits
Pabst, O., Hornef, M. W., Schaap, F. G., Cerovic, V., Clavel, T., & Bruns, T. (2023) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-023-00771-6 · Cited by 488
“…substrate 212 ; acetate acts as a precursor in lipogenesis and cholesterol biosynthesis in the liver and propionate is used for gluconeogenesis 213,214 ; improvement of epithelial barrier function, enhanced mucus thickness and release of antimicrobial peptides 87,209 ; and reciprocal…”
BackgroundYin, K., Wang, Y., Zhao, H., Wang, D., Guo, M., Mu, M., Liu, Y., Nie, X., Li, B., Li, J., et al. (2021) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2021.145758 · Cited by 447
Multiple Parallel Hits Hypothesis in Nonalcoholic Fatty Liver Disease: Revisited After a Decade
Tilg, H., Adolph, T. E., & Moschen, A. R. (2020) · Hepatology · doi:10.1002/hep.31518 · Cited by 455
“(78) Fructose intake triggers de novo lipogenesis in the liver, and this process also involves microbiota-derived acetate.(79) A recent study in 10 healthy subjects, however, with excess isocaloric fructose consumption for 8 weeks showed no detrimental metabolic effects including the liver.”
BackgroundLipogenesis inhibitors: therapeutic opportunities and challenges
Batchuluun, B., Pinkosky, S. L., & Steinberg, G. R. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00367-2 · Cited by 419
The links between gut microbiota and obesity and obesity related diseases
Geng, J., Ni, Q., Sun, W., Li, L., & Feng, X. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.112678 · Cited by 422
Precision medicine in the era of artificial intelligence: implications in chronic disease management
Subramanian, M., Wojtusciszyn, A., Favre, L., Boughorbel, S., Shan, J., Letaief, K. B., Pitteloud, N., & Chouchane, L. (2020) · Journal of Translational Medicine · doi:10.1186/s12967-020-02658-5 · Cited by 362
“A recent elegant study has revealed that intestinal microbiota plays a major role in converting the dietary fructose to acetate, which in turn activates the hepatic lipogenesis [48, 49].”
BackgroundDietary sugar consumption and health: umbrella review
Huang, Y., Chen, Z., Chen, B., Li, J., Yuan, X., Li, J., Wang, W., Dai, T., Chen, H., Wang, Y., et al. (2023) · BMJ · doi:10.1136/bmj-2022-071609 · Cited by 348
“96 Intermediate products such as diacylglycerols generated during the process of lipogenesis may impair insulin signalling in the liver and peripheral tissues and then lead to insulin resistance.”
BackgroundFinley, L. W. S. (2023) · Cell · doi:10.1016/j.cell.2023.01.038 · Cited by 343
Acetyl-CoA metabolism in cancer
Guertin, D. A., & Wellen, K. E. (2023) · Nature Reviews Cancer · doi:10.1038/s41568-022-00543-5 · Cited by 303
Self-citationMolecular aspects of fructose metabolism and metabolic disease
Herman, M. A., & Birnbaum, M. J. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2021.09.010 · Cited by 315
Vallianou, N. G., Christodoulatos, G. S., Karampela, Ι., Tsilingiris, D., Magkos, F., Stratigou, T., Kounatidis, D. C., & Dalamaga, Μ. (2021) · Biomolecules · doi:10.3390/biom12010056 · Cited by 305
Hong, Y., Sheng, L., He, X., Zhong, J., Ma, J., 赵爱华, Zheng, X., Gu, Y., Yao, J., Li, Y., et al. (2021) · Gut Microbes · doi:10.1080/19490976.2021.1930874 · Cited by 287
“for lipid production.(39) These findings provide a new perspective on the relationship between diet, flora and host metabolism in fatty liver and other metabolic diseases.”
BackgroundSelf-citationBacteroides utilization for dietary polysaccharides and their beneficial effects on gut health
Cheng, J., Hu, J., Geng, F., & Nie, S. (2022) · Food Science and Human Wellness · doi:10.1016/j.fshw.2022.04.002 · Cited by 291
Geidl-Flueck, B., Hochuli, M., Németh, Á., Eberl, A., Derron, N., Köfeler, H. C., Tappy, L., Berneis, K., Spinas, G. A., & Gerber, P. A. (2021) · Journal of Hepatology · doi:10.1016/j.jhep.2021.02.027 · Cited by 238
“acetate.(14) Contrasting with our hypothesis, fructose and sucrose likewise increase the FSR.”
BackgroundInfluentialHur, J., Otegbeye, E., Joh, H.-K., Nimptsch, K., Ng, K., Ogino, S., Meyerhardt, J. A., Chan, A. T., Willett, W. C., Wu, K., et al. (2021) · Gut · doi:10.1136/gutjnl-2020-323450 · Cited by 229
Integrative metabolism in MASLD and MASH: Pathophysiology and emerging mechanisms
Steinberg, G. R., Valvano, C. M., De Nardo, W., & Watt, M. J. (2025) · Journal of Hepatology · doi:10.1016/j.jhep.2025.02.033 · Cited by 240
Zhang, S., Zhao, J., Xie, F., He, H., Johnston, L. J., Dai, X., Wu, C., & Ma, X. (2021) · Obesity Reviews · doi:10.1111/obr.13316 · Cited by 223
Gut bacterial nutrient preferences quantified in vivo
Zeng, X., Xing, X., Gupta, M., Keber, F. C., Lopez, J. G., Lee, Y.-C. J., Roichman, A., Wang, L., Neinast, M. D., Donia, M. S., et al. (2022) · Cell · doi:10.1016/j.cell.2022.07.020 · Cited by 208
Self-citationInhibition of ATP-citrate lyase improves NASH, liver fibrosis, and dyslipidemia
Morrow, M. R., Batchuluun, B., Wu, J., Ahmadi, E., Leroux, J. M., Mohammadi-Shemirani, P., Desjardins, E. M., Wang, Z., Tsakiridis, E. E., Lavoie, D. C. T., et al. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.05.004 · Cited by 199
Moonlighting functions of metabolic enzymes and metabolites in cancer
Pan, C., Li, B., & Simon, M. C. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.08.031 · Cited by 198
Im, Y. R., Hunter, H., de Gracia Hahn, D., Duret, A., Cheah, Q., Dong, J., Fairey, M., Hjalmarsson, C., Li, A., Lim, H. K., et al. (2021) · Hepatology · doi:10.1002/hep.31897 · Cited by 195
Western diets and chronic diseases
Adolph, T. E., & Tilg, H. (2024) · Nature Medicine · doi:10.1038/s41591-024-03165-6 · Cited by 224
“…mediated by adaptive immunity 159,164,165 , by metabolic responses in hepatocytes 160,201 and by gut microbial fructose metabolism into acetate 162 . d , A fructose-enriched diet and fructose metabolism promote intestinal tumor growth 198 , similar to a high-fat diet 192 , partly by…”
Fructose reprogrammes glutamine-dependent oxidative metabolism to support LPS-induced inflammation
Jones, N., Blagih, J., Zani, F., Rees, A., Hill, D. G., Jenkins, B., Bull, C. J., Moreira, D., Bantan, A., Cronin, J., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-21461-4 · Cited by 190
Acetyl-CoA Metabolism and Histone Acetylation in the Regulation of Aging and Lifespan
Bradshaw, P. C. (2021) · Antioxidants · doi:10.3390/antiox10040572 · Cited by 189
“This acetate was converted into acetyl-CoA by hepatic ACSS2 contributing to increased fatty acid synthesis and fatty liver [75].”
Moffett, J. R., Puthillathu, N., Vengilote, R., Jaworski, D. M., & Namboodiri, A. M. A. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.580167 · Cited by 190
“small intestine, but rather, some passes on to the colon where it is fermented into short-chain fatty acids, especially acetate (Zhao et al., 2020).”
Background“Sweet death”: Fructose as a metabolic toxin that targets the gut-liver axis
Febbraio, M. A., & Karin, M. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2021.09.004 · Cited by 185
“, 2020), using comparatively low amounts of fructose, found that enterocyte-specific KHK-C deficiency was not protective, but hepatic steatosis was quite low in these experiments, as also observed previously (Zhao et al., 2020).”
BackgroundResultInfluentialThe small intestine shields the liver from fructose-induced steatosis
Jang, C., Wada, S., Yang, S. H., Gosis, B. S., Zeng, X., Zhang, Z., Shen, Y., Lee, G., Arany, Z. P., & Rabinowitz, J. D. (2020) · Nature Metabolism · doi:10.1038/s42255-020-0222-9 · Cited by 175
Self-citationMuriel, P., López‐Sánchez, P., & Ramos‐Tovar, E. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22136969 · Cited by 171
“Similarly, diets enriched with fructose alter the composition of the short-chain fatty acids in the gut, inducing a high microbial production of butyrate, acetate or propionate by the intestinal microbiota, therefore increasing the production of acetyl-CoA from acetate, which contributes to lipogenesis [82].”
BackgroundShort-chain fatty acids activate acetyltransferase p300
Thomas, S. P., & Denu, J. M. (2021) · eLife · doi:10.7554/elife.72171 · Cited by 168
Developing dietary interventions as therapy for cancer
Taylor, S. R., Falcone, J. N., Cantley, L. C., & Goncalves, M. D. (2022) · Nature reviews. Cancer · doi:10.1038/s41568-022-00485-y · Cited by 168
Fructose contributes to the Warburg effect for cancer growth
Nakagawa, T., Lanaspa, M. A., Millán, Í. S., Fini, M. A., Rivard, C. J., Sánchez‐Lozada, L. G., Andrés-Hernando, A., Tolan, D. R., & Johnson, R. J. (2020) · Cancer & Metabolism · doi:10.1186/s40170-020-00222-9 · Cited by 151
“showed using mice that dietary fructose is converted to acetate by the gut microbiota [40].”
BackgroundIizuka, K., Takao, K., & Yabe, D. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.587189 · Cited by 159
“ChREBP also induces Acss2 expression (Figure 1) (14, 29, 33).”
BackgroundMitochondria-rough-ER contacts in the liver regulate systemic lipid homeostasis
Anastasia, I., Ilacqua, N., Raimondi, A., Lemieux, P., Ghandehari‐Alavijeh, R., Faure, G., Mekhedov, S., Williams, K. J., Caicci, F., Valle, G., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.108873 · Cited by 157
NAD precursors cycle between host tissues and the gut microbiome
Chellappa, K., McReynolds, M. R., Lu, W., Zeng, X., Makarov, M., Hayat, F., Mukherjee, S., Bhat, Y. R., Lingala, S. R., Shima, R. T., et al. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.11.004 · Cited by 146
Self-citationThe Role of Gut–Liver Axis in Gut Microbiome Dysbiosis Associated NAFLD and NAFLD-HCC
Song, Q., & Zhang, X. (2022) · Biomedicines · doi:10.3390/biomedicines10030524 · Cited by 154
“However, there is a controversial study showing microbiota-derived acetate can promote hepatic lipogenesis [40].”
BackgroundFougerat, A., Montagner, A., Loiseau, N., Guillou, H., & Wahli, W. (2020) · Cells · doi:10.3390/cells9071638 · Cited by 150
“This pathway results in lipogenic pools of acetyl-CoA [67].”
BackgroundDietary Fructose and Fructose-Induced Pathologies
Jung, S., Bae, H., Song, W., & Jang, C. (2022) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-062220-025831 · Cited by 158
Self-citationRecent advances in fructose intake and risk of hyperuricemia
Zhang, C., Li, L., Zhang, Y., & Zeng, C. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.110795 · Cited by 145
Wang, J., Yang, Y., Shao, F., Meng, Y., Guo, D. S., He, J., & Lu, Z. (2024) · Nature Metabolism · doi:10.1038/s42255-024-01037-4 · Cited by 144
Acetylcarnitine shuttling links mitochondrial metabolism to histone acetylation and lipogenesis
Izzo, L., Trefely, S., Demetriadou, C., Drummond, J. M., Mizukami, T., Kuprasertkul, N., Farria, A. T., Nguyen, P. T., Murali, N., Reich, L. N., et al. (2023) · Science Advances · doi:10.1126/sciadv.adf0115 · Cited by 140
“Last, although glucose use for fatty acid synthesis is strongly suppressed in the absence of ACLY, it is not fully blocked in vitro or in vivo ( 4 , 6 ).”
Self-citationIntestinal dysbiosis in nonalcoholic fatty liver disease (NAFLD): focusing on the gut–liver axis
Han, H. L., Jiang, Y., Wang, M., Melaku, M., Liu, L., Zhao, Y. M., Everaert, N., Yi, B., & Zhang, H. (2021) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2021.1966738 · Cited by 135
Serine catabolism generates liver NADPH and supports hepatic lipogenesis
Zhang, Z., TeSlaa, T. A., Xu, X., Zeng, X., Yang, L., Xing, G., Tesz, G. J., Clasquin, M. F., & Rabinowitz, J. D. (2021) · Nature Metabolism · doi:10.1038/s42255-021-00487-4 · Cited by 130
Self-citationShort‐chain fatty acids: bridges between diet, gut microbiota, and health
Wang, L., He, L., Xu, L., & Li, S. (2024) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.16619 · Cited by 146
Joh, H.-K., Lee, D. H., Hur, J., Nimptsch, K., Chang, Y., Joung, H., Zhang, X., Rezende, L. F. M., Lee, J. E., Ng, K., et al. (2021) · Gastroenterology · doi:10.1053/j.gastro.2021.03.028 · Cited by 122
Zhou, P., Chang, W.-Y., Gong, D.-A., Xia, J. L., Chen, W., Huang, L., Liu, R., Liu, Y., Chen, C., Wang, K., et al. (2023) · Cell Metabolism · doi:10.1016/j.cmet.2023.09.009 · Cited by 122
Amino acid is a major carbon source for hepatic lipogenesis
Liao, Y., Chen, Q., Liu, L., Huang, H., Sun, J., Bai, X., Jin, C., Li, H., Sun, F., Xiao, X., et al. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2024.10.001 · Cited by 133
MASH: the nexus of metabolism, inflammation, and fibrosis
Steinberg, G. R., Carpentier, A. C., & Wang, D. (2025) · Journal of Clinical Investigation · doi:10.1172/jci186420 · Cited by 135
“These actions on multiple cell types within the liver may explain in part the discordant findings between beneficial effects with pharmacological inhibitors and the benign or detrimental findings with hepatocyte-selective genetic inhibition of these targets (109, 143–145).”
InfluentialSchnabl, B., Damman, C. J., & Carr, R. M. (2025) · Journal of Clinical Investigation · doi:10.1172/jci186423 · Cited by 133
“In short, excess carbohydrate consumption can significantly disrupt the intestinal barrier and should be avoided (24).”
Zhang, Y., Cao, M., Li, Y., Dai, G.-C., Lu, P., Zhang, M., Bai, L., Chen, X.-X., Zhang, C., Shi, L., et al. (2022) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2022.2047005 · Cited by 113
The key role of altered tubule cell lipid metabolism in kidney disease development
Lee, L. E., Doke, T., Mukhi, D., & Suszták, K. (2024) · Kidney International · doi:10.1016/j.kint.2024.02.025 · Cited by 120
The Microbiota and the Gut–Brain Axis in Controlling Food Intake and Energy Homeostasis
Romaní‐Pérez, M., Bullich‐Vilarrubias, C., López‐Almela, I., Liébana-García, R., Olivares, M., & Sanz, Y. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22115830 · Cited by 117
“Gavage of [13C]fructose in mice reveals that high doses of fructose saturate the fructose-to-glucose conversion in the small intestine, enhancing fructose utilization by the microbiota in the colon via the hexokinase pathway to further generate tricarboxylic acid cycle (TCA) intermediates, such as essential amino acid…”
BackgroundThe role of ChREBP in carbohydrate sensing and NAFLD development
Régnier, M., Carbinatti, T., Parlati, L., Benhamed, F., & Postic, C. (2023) · Nature Reviews Endocrinology · doi:10.1038/s41574-023-00809-4 · Cited by 101
Beisner, J., Gonzalez‐Granda, A., Basrai, M., Damms-Machado, A., & Bischoff, S. C. (2020) · Nutrients · doi:10.3390/nu12113444 · Cited by 106
“Keywords: fructose; microbiota; host-microbe interactions; obesity; metabolic syndrome; NAFLD”
BackgroundInfluentialKrause, N., & Wegner, A. (2020) · Cells · doi:10.3390/cells9122635 · Cited by 103
“Recently, Zhao and colleagues, however, showed that the microbiome contributes to the supply of lipogenic acetyl-CoA by converting fructose to acetate [81].”
BackgroundMethodInfluentialHou, Y., Wei, W., Guan, X., Liu, Y., Bian, G., He, D., Fan, Q., Cai, X., Zhang, Y., Wang, G., et al. (2021) · Nature Communications · doi:10.1038/s41467-020-20673-4 · Cited by 101
Gut and Vaginal Microbiomes in PCOS: Implications for Women’s Health
Gu, Y., Zhou, G., Zhou, F., Li, Y. O., Wu, Q., He, H., Zhang, Y., Ma, C., Ding, J., & Hua, K. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.808508 · Cited by 106
“The gut microbiota is proved to be involved in the production of acetate (21), butyrate, and propionate (22), which are main short-chain fatty acids with effect of antiinflammatory, anticarcinogenic, and immunomodulatory.”
BackgroundYang, Z., Su, H., Lv, Y., Tao, H., Jiang, Y., Ni, Z., Peng, L., & Chen, X. (2022) · Food Research International · doi:10.1016/j.foodres.2022.112309 · Cited by 102
Research progress in the role and mechanism of Leucine in regulating animal growth and development
Rehman, S. U., Ali, R., Zhang, H., Zafar, M. H., & Wang, M. (2023) · Frontiers in Physiology · doi:10.3389/fphys.2023.1252089 · Cited by 113
The pathophysiology of MASLD: an immunometabolic perspective
Schwärzler, J., Grabherr, F., Grander, C., Adolph, T. E., & Tilg, H. (2023) · Expert Review of Clinical Immunology · doi:10.1080/1744666x.2023.2294046 · Cited by 107
Endothelium‐derived lactate is required for pericyte function and blood–brain barrier maintenance
Lee, H., Xu, Y., Zhu, X., Jang, C., Choi, W., Bae, H., Wang, W., He, L., Jin, S., Arany, Z. P., et al. (2022) · The EMBO Journal · doi:10.15252/embj.2021109890 · Cited by 97
“The liquid chromatography-MS (LC – MS) analysis was performed as previously described (Zhao et al , 2020).”
Self-citationDiet-induced gut dysbiosis and inflammation: Key drivers of obesity-driven NASH
Kang, G. G., Trevaskis, N. L., Murphy, A. J., & Febbraio, M. A. (2023) · iScience · doi:10.1016/j.isci.2022.105905 · Cited by 94
High-Fructose Diet Increases Inflammatory Cytokines and Alters Gut Microbiota Composition in Rats
Wang, Y., Qi, W., Song, G., Pang, S., Peng, Z., Li, Y., & Wang, P. (2020) · Mediators of Inflammation · doi:10.1155/2020/6672636 · Cited by 103
“Evidence showed that consumption of HFCS in beverages and processed foods induced development of nonalcoholic fatty liver disease (NAFLD) and chronic inflammation [5].”
BackgroundThe Therapeutic Effect of SCFA-Mediated Regulation of the Intestinal Environment on Obesity
You, H., Tan, Y., Yu, D., Qiu, S., Bai, Y., He, J., Cao, H., Che, Q., Guo, J., & Su, Z. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2022.886902 · Cited by 99
A key genetic factor governing arabinan utilization in the gut microbiome alleviates constipation
Zhang, C., Yu, L., Ma, C., Jiang, S., Zhang, Y., Wang, S., Tian, F., Xue, Y., Zhao, J., Zhang, H., et al. (2023) · Cell Host & Microbe · doi:10.1016/j.chom.2023.10.011 · Cited by 98
Early-onset colorectal cancer: Current insights and future directions
Wu, C. W., & Lui, R. N.-S. (2022) · World Journal of Gastrointestinal Oncology · doi:10.4251/wjgo.v14.i1.230 · Cited by 90
Acetyl-CoA synthetase 2(ACSS2): a review with a focus on metabolism and tumor development
Ling, R., Chen, G., Tang, X., Liu, N., Zhou, Y., & Chen, D. (2022) · Discover Oncology · doi:10.1007/s12672-022-00521-1 · Cited by 95
“This acetate is then used to produce acetyl-CoA via hepatic ACSS2, promoting fatty acid synthesis and fostering the formation of fatty liver [46].”
MethodEmerging connections between gut microbiome bioenergetics and chronic metabolic diseases
Daisley, B. A., Koenig, D. W., Engelbrecht, K. C., Doney, L., Hards, K., Al, K. F., Reid, G., & Burton, J. P. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.110087 · Cited by 87
The Role of Fructose in Non-Alcoholic Steatohepatitis: Old Relationship and New Insights
Federico, A., Rosato, V., Masarone, M., Torre, P., Dallio, M., Romeo, M., & Persico, M. (2021) · Nutrients · doi:10.3390/nu13041314 · Cited by 82
Tissue-Specific Fructose Metabolism in Obesity and Diabetes
Helsley, R. N., Moreau, F., Gupta, M. K., Radulescu, A., DeBosch, B. J., & Softic, S. (2020) · Current Diabetes Reports · doi:10.1007/s11892-020-01342-8 · Cited by 80
Gut microbiome in gastrointestinal cancer: a friend or foe?
Liu, Y., Baba, Y., Ishimoto, T., Gu, X. J., Zhang, J., Nomoto, D., Okadome, K., Baba, H., & Qiu, P. (2022) · International Journal of Biological Sciences · doi:10.7150/ijbs.69331 · Cited by 82
“Dietary cholesterol induces an increase in taurocholic acid and a decrease in indole propionic acid which drive the occurrence of NAFLD-HCC [66].”
BackgroundLinks between gut microbiome composition and fatty liver disease in a large population sample
Ruuskanen, M. O., Åberg, F. O., Männistö, V., Havulinna, A. S., Méric, G., Liu, Y., Loomba, R. S., Vázquez‐Baeza, Y., Tripathi, A., Valsta, L. M., et al. (2021) · Gut Microbes · doi:10.1080/19490976.2021.1888673 · Cited by 78
Dysregulation of Lipid and Glucose Metabolism in Nonalcoholic Fatty Liver Disease
Bhat, N., & Mani, A. (2023) · Nutrients · doi:10.3390/nu15102323 · Cited by 85
“Furthermore, gut microbiota-derived acetate has recently been shown to increase DNL in response to dietary fructose [46].”
BackgroundA Review of the Relationship between Gut Microbiome and Obesity
Zsálig, D., Berta, A., Tóth, V., Szabó, Z., Klara, S. M., Figler, M., Pusztafalvi, H., & Polyák, É. (2023) · Applied Sciences · doi:10.3390/app13010610 · Cited by 79
“The acetate produced functions as a precursor for acetyl-CoA and fatty acids for de novo lipogenesis in the liver, thus, the overproduction of acetate may contribute to obesity [86].”
Butyrate and obesity: Current research status and future prospect
Peng, K., Dong, W., Luo, T., Tang, H., Zhu, W., Huang, Y., & Yang, X. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1098881 · Cited by 81
“Acetate also contributes to the synthesis of cholesterol and the synthesis of lipids in liver (22, 23).”
BackgroundDeciphering the gut microbiome of grass carp through multi-omics approach
Li, M., Liang, H., Yang, H., Ding, Q., Xia, R., Chen, J., Zhou, W., Yang, Y., Zhang, Z., Yao, Y., et al. (2024) · Microbiome · doi:10.1186/s40168-023-01715-7 · Cited by 79
“Studies have confirmed that the gut microbiota is able to ferment dietary fiber to produce short-chain fatty acids (e.g., acetate) that modulate lipid metabolism in the host [54, 65].”
BackgroundObesogens: How They Are Identified and Molecular Mechanisms Underlying Their Action
Mohajer, N., Du, C. Y., Checkcinco, C., & Blumberg, B. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.780888 · Cited by 72
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
Tappy, L. (2020) · Clinical Nutrition · doi:10.1016/j.clnu.2020.12.022 · Cited by 80
Sun, S., Araki, Y., Hanzawa, F., Umeki, M., Kojima, T., Nishimura, N., Ikeda, S., Mochizuki, S., & Oda, H. (2021) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2021.108621 · Cited by 69
Mannose Treatment: A Promising Novel Strategy to Suppress Inflammation
Zhang, W., Cheng, H., Gui, Y., Zhan, Q., Li, S., Qiao, W., & Tong, A. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.756920 · Cited by 71
“For example, one study reported that glucose-fructose syrup (HFCS) enhances intestinal tumor growth in mice via activation of glycolysis and increased synthesis of fatty acids in tumor cells that support tumor growth (1); Another study found that high fructose intake is associated with increased hepatic fatty acid syn…”
BackgroundIntegrated Multi‐Cohort Analysis of the Parkinson's Disease Gut Metagenome
Boktor, J. C., Sharon, G., Metman, L. V., Hall, D. A., Engen, P. A., Zreloff, Z. J., Hakim, D., Bostick, J. W., Ousey, J. A., Lange, D., et al. (2023) · Movement Disorders · doi:10.1002/mds.29300 · Cited by 67
“Microbial metabolites influence the function of the metabolic, immune, and nervous systems in animals and humans.(46-48) We inferred the microbial metabolic potential of the PD microbiome through MetaCyc pathway abundance.”
BackgroundThe gut–liver axis: host microbiota interactions shape hepatocarcinogenesis
Silveira, M. A. D., Bilodeau, S., Greten, T. F., Wang, X. W., & Trinchieri, G. (2022) · Trends in cancer · doi:10.1016/j.trecan.2022.02.009 · Cited by 69
Lund, P. J., Gates, L. A., Leboeuf, M., Smith, S. A., Chau, L., Lopes, M. D. C., Friedman, E. S., Saiman, Y., Kim, M. S., Shoffler, C. A., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111809 · Cited by 71
The differences in carbohydrate utilization ability between six rounds of Sauce-flavor Daqu
Zhu, Q., Chen, L., Peng, Z., Zhang, Q., Huang, W., Yang, F., Du, G., Zhang, J., & Wang, L. (2022) · Food Research International · doi:10.1016/j.foodres.2022.112184 · Cited by 63
Fang, J., Chen, J., Zheng, J.-L., Zeng, H.-X., Chen, J.-G., Wu, C.-H., Cai, J.-L., Wang, Z., & Zhuang, S. (2023) · Cancer Research · doi:10.1158/0008-5472.can-22-1844 · Cited by 65
The Contribution of Dietary Fructose to Non-alcoholic Fatty Liver Disease
Yu, S., Li, C., Ji, G., & Zhang, L. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.783393 · Cited by 66
“The metabolites of fructose in the intestine, such as SCFA, and amino acid also provide substrates for hepatic DNL, leading to the lipid accumulation in hepatocytes and the increase of circulating fatty acids (Jang et al., 2018; Jahn et al., 2019; Zhao et al., 2020) (Figure 2).”
BackgroundComparison of Different Soluble Dietary Fibers during the In Vitro Fermentation Process
Bai, J., Li, Y., Li, T., Zhang, W., Fan, M., Zhang, K., Qian, H., Zhang, H., Qi, X., & Wang, L. (2021) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.1c00237 · Cited by 62
A small molecule targeting ALOX12-ACC1 ameliorates nonalcoholic steatohepatitis in mice and macaques
Zhang, X., Ji, Y., Cheng, Y., Cheng, Y., Wang, J., Wang, J., Zhao, L., Huang, Y., Sun, D., Xiang, H., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abg8116 · Cited by 61
Zhu, C., Huai, Q., Zhang, X., Dai, H., Li, X., & Wang, H. (2022) · International Journal of Biological Sciences · doi:10.7150/ijbs.78525 · Cited by 59
“Depletion of the microbiota or silencing of hepatic acetate-CoA synthetase 2, which generates acetyl-CoA from acetate, potently suppresses the conversion of bolus fructose into hepatic acetyl-CoA and fatty acids [36].”
BackgroundThe fructose survival hypothesis for obesity
Johnson, R. J., Lanaspa, M. A., Sánchez‐Lozada, L. G., Tolan, D. R., Nakagawa, T., Ishimoto, T., Andrés-Hernando, A., Rodríguez‐Iturbe, B., & Stenvinkel, P. (2023) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2022.0230 · Cited by 64
“The inhibition of aconitase stimulates the enzymes involved in lipogenesis [41,49] while acetate production by the microbiota in response to fructose is used to generate acetyl CoA that provides the substrate.”
BackgroundAdded Fructose in Non-Alcoholic Fatty Liver Disease and in Metabolic Syndrome: A Narrative Review
Coronati, M., Baratta, F., Pastori, D., Ferro, D., Angelico, F., & Ben, M. D. (2022) · Nutrients · doi:10.3390/nu14061127 · Cited by 61
“In addition, in the intestinal lumen, fructose undergoes the gut microbiota action and is converted into acetate, which supplies lipogenic acetyl-CoA independently of the fructolytic metabolic processes [51].”
BackgroundReprogramming 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
Metadata
- Authors
- Zhao, S., Jang, C., Liu, J., Uehara, K., Gilbert, M., Izzo, L., Zeng, X., Trefely, S., Fernandez, S., Carrer, A., Miller, K. D., Schug, Z. T., Snyder, N. W., Gade, T. P., Titchenell, P. M., Rabinowitz, J. D., & Wellen, K. E.
- Affiliations
- University of Pennsylvania (US)
- Princeton University (US)
- Veneto Institute of Molecular Medicine (IT)
- The Wistar Institute (US)
- Temple University (US)
- Corresponding author
- Wellen, Kathryn E.
- ORCID
- Venue
- Nature
- Published
- 2020-03-18
- Volume
- 579
- Issue
- 7800
- Pages
- 586-591
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC7416516
- OpenAlex
- W3012090404
- Cited by
- 553
- References
- 50
- Citations by year
- 2026: 61 · 2025: 90 · 2024: 91 · 2023: 96 · 2022: 91 · 2021: 82 · 2020: 42
- FWCI
- 59.64
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Padua Research Archive (University of Padova) (submittedVersion)
- Funders
- National Cancer Institute (T32CA115299, R01CA174761, F99CA222741, R01CA228339, T32CA009171, P30CA010815)
- National Institute of General Medical Sciences (R01GM132261, T32GM007229, K12GM081259)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK116005, DP1DK113643, K01DK111715, P30DK019525, T32DK007314)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (T32AR053461)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R03HD092630)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Keywords
- dietary fructose, hepatic lipogenesis, de novo lipogenesis, gut microbiota, acetate, acetyl-CoA, ATP citrate lyase, ACSS2, fructolysis, non-alcoholic fatty liver disease, obesity, isotope tracing, lipogenic gene expression, fructose absorption
- MeSH terms
- Gastrointestinal Microbiome, Dietary Sugars, Acetates, Acetyl Coenzyme A, Acetate-CoA Ligase, Animals, ATP Citrate (pro-S)-Lyase, Fatty Acids, Fructose, Gene Expression Regulation, Isotope Labeling, Liver, Male, Substrate Specificity, Citric Acid, Hepatocytes, Lipogenesis, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
