Cited by 577Diet, Metabolism, and DiseaseLipid metabolism and biosynthesisLiver Disease Diagnosis and Treatment

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 access

Zhao, Steven, Jang, Cholsoon, Liu, Joyce, Uehara, Kahealani, Gilbert, Michael, Izzo, Luke, Zeng, Xianfeng, Trefely, Sophie, Fernandez, Sully, Carrer, Alessandro, Miller, Katelyn D., Schug, Zachary T., Snyder, Nathaniel W., Gade, Terence P., Titchenell, Paul M., Rabinowitz, Joshua D., Wellen, Kathryn E.·2020·Nature

DOI 10.1038/s41586-020-2101-7PMC PMC7416516

Open this paper in CoChat — free account

Abstract

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.

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

Crossref · 10.1038/s41586-020-2101-7

Cites

50 of 51 references verified1 citation errors · 0 not checkable

Statistics

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?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

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
Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease
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
Determination of bacterial load by real-time PCR using a broad-range (universal) probe and primers set
Nadkarni, M. A., Martin, F. E., Jacques, N. A., & Hunter, N. (2002) · Microbiology · doi:10.1099/00221287-148-1-257 · Cited by 1,931
Dual Roles for Glucokinase in Glucose Homeostasis as Determined by Liver and Pancreatic β Cell-specific Gene Knock-outs Using Cre Recombinase
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
Increased de novo lipogenesis is a distinct characteristic of individuals with nonalcoholic fatty liver disease
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
The Warburg Effect Dictates the Mechanism of Butyrate-Mediated Histone Acetylation and Cell Proliferation
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

Show all 50 references

Sorted by citations

Items 201–300 of 577

Acetate and succinate benefit host muscle energetics as exercise‐associated post‐biotics
Ismaeel, A., Valentino, T. R., Burke, B. I., Goh, J. Z., Saliu, T. P., Albathi, F. A., Owen, A. M., McCarthy, J. J., & Wen, Y. (2023) · Physiological Reports · doi:10.14814/phy2.15848 · Cited by 26
“Microbial-derived SCFAs, including acetate, have been shown to benefit multiple host organs (Perry et al., 2016; Zhao et al., 2020; Zheng et al., 2021), including muscle mass and function (Lahiri et al., 2019; Sakakida et al., 2022).”
Background
Hawthorn total flavonoids ameliorate hyperlipidemia through AMPK / SREBP1 ‐c and PPAR α/ PGC ‐1α/ CPT ‐ 1A pathway activation and gut microbiota modulation
Zheng, L., Lü, Z., Ma, Y., Cui, P., Zhang, X., Gan, J., & Li, G. (2025) · Journal of the Science of Food and Agriculture · doi:10.1002/jsfa.14188 · Cited by 22
“38 In addition, some studies have demonstrated that probiotics can accelerate bile acid circulation, consume more cholesterol for the synthesis of bile acid, and signi ﬁ cantly improve the distribution of lipids in serum and liver.”
Dual inhibition of hepatic ACLY and ACSS2: A synergistic approach to combat NAFLD through lipogenesis reduction and mitochondrial enhancement
Zhang, M., Ji, J., Lei, Y., Qin, F., Tao, Y., Li, N., Bian, J., Li, Z., Lai, M., & Qiu, Z. (2025) · Pharmacological Research · doi:10.1016/j.phrs.2025.107706 · Cited by 23
Special correlation between diet and MASLD: positive or negative?
Liu, J., Li, C., Yang, Y., Li, J., Sun, X., Zhang, Y., Liu, R., Chen, F., & Li, X. (2025) · Cell & Bioscience · doi:10.1186/s13578-025-01382-1 · Cited by 29
“…by upregulating malic enzyme 1 and acyl-CoA synthetase long-chain family member 1, which promoted hepatic de novo lipogenesis (DNL) and triglyceride accumulation, while enhancing Acyl-CoA synthetase short-chain family member 2-mediated acetate-to-acetyl-CoA conversion to amplify lipogenesis [90].”
Self-citation
Regulation of the gut barrier by carbohydrates from diet – Underlying mechanisms and possible clinical implications
Bischoff, S. C., Kaden-Volynets, V., Rosa, L. F., Guseva, D., & Seethaler, B. (2021) · International Journal of Medical Microbiology · doi:10.1016/j.ijmm.2021.151499 · Cited by 23
The Impact of Gut Microbiome on Maternal Fructose Intake-Induced Developmental Programming of Adult Disease
Hsu, C., Yu, H., Chan, J. Y. H., Wu, K. L. H., Lee, W., & Tain, Y. (2022) · Nutrients · doi:10.3390/nu14051031 · Cited by 23
“Fructose is absorbed in the gut through facilitated glucose transporters 5 (Glut 5) and Glut 2 [6] and almost entirely metabolized in the liver [12].”
Background
High-fat diet-induced gut microbiota alteration promotes lipogenesis by butyric acid/miR-204/ACSS2 axis in chickens
Chen, C., Chen, W., Ding, H., Wu, P., Zhang, G., Xie, K., & Zhang, T. (2023) · Poultry Science · doi:10.1016/j.psj.2023.102856 · Cited by 23
“Although previous studies have demonstrated the significant roles of gut microbiota in regulating animal lipogenesis and fat deposition (Zhao et al., 2020; Chen et al., 2021; Heo et al., 2023), there is a paucity of studies examining the correlations between gut microbiota and chicken lipogenesis.”
Result
The Impact and Burden of Dietary Sugars on the Liver
Huneault, H. E., Tovar, A. R., Sanchez-Torres, C., Welsh, J. A., & Vos, M. B. (2023) · Hepatology Communications · doi:10.1097/hc9.0000000000000297 · Cited by 27
“[56] Acetate can enter the portal circulation and be converted to acetyl-CoA by acetyl-CoA synthetase in the liver, potentially providing more carbon sources for de novo lipogenesis.”
Background
NASH, Fibrosis and Hepatocellular Carcinoma: Lipid Synthesis and Glutamine/Acetate Signaling
Sunami, Y. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21186799 · Cited by 24
“Acss2 using an adeno-associated viral (AAV) hairpin targeting Acss2 suppresses FA synthesis from fructose [93].”
Method
Organismal Fructose Metabolism in Health and Non-Alcoholic Fatty Liver Disease
Skenderian, S., Park, G. S. H., & Jang, C. (2020) · Biology · doi:10.3390/biology9110405 · Cited by 24
“Using antibiotics treatment and the liver-specific knockdown of Acyl-coenzyme A synthetase short-chain family member 2 (ACSS2), which is the essential enzyme for acetate catabolism, they showed that depletion of the microbiota or suppression of ACSS2 dramatically reduced fructose carbon incorporation into hepatic acet…”
BackgroundInfluentialSelf-citation
Dual inhibition of ACLY and ACSS2 by EVT0185 reduces steatosis, hepatic stellate cell activation, and fibrosis in mouse models of MASH
Steinberg, G. R., Gautam, J., Lally, J., Fayyazi, R., Grasset, E., Bhattacharya, D., Fidelito, G., Ahmadi, E., Townsend, L. K., Batchuluun, B., et al. (2026) · Cell Metabolism · doi:10.1016/j.cmet.2025.11.015 · Cited by 23
Bacillus licheniformis FA6 Affects Zebrafish Lipid Metabolism through Promoting Acetyl-CoA Synthesis and Inhibiting β-Oxidation
Chen, S., Ye, W., Clements, K. D., Zan, Z., Zhao, W., Zou, H., Wang, G., & Wu, S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms24010673 · Cited by 24
“The SCFA acetate is transported to the liver to generate acetyl-CoA through activity of acyl-CoA synthase short-chain family member 2, and acetate is also an important source for lipogenesis in the liver [12,13].”
Background
Activation of acetyl-CoA synthetase 2 mediates kidney injury in diabetic nephropathy
Lu, J., Li, X. Q., Chen, P. P., Zhang, J. X., Liu, L., Wang, G. H., Liu, X. Q., Jiang, T. T., Wang, M. Y., Liu, W. T., et al. (2023) · JCI Insight · doi:10.1172/jci.insight.165817 · Cited by 24
“Previous studies have revealed the epigenetically mediated potential of ACSS2 in gene expression concerning energy metabolism (21, 22).”
Background
Metabolic Insights into Caffeine’s Anti-Adipogenic Effects: An Exploration through Intestinal Microbiota Modulation in Obesity
Fortunato, I. M., Pereira, Q. C., Oliveira, F. D. S., Alvarez, M. C., dos Santos, T. W., & Ribeiro, M. L. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25031803 · Cited by 24
“Its exacerbated increase may be involved in obesity and liver diseases related to non-alcoholic fats [74–77].”
Background
Mechanisms and therapeutic insights into MASH-associated fibrosis
Zhu, Y., & Cai, B. (2025) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2025.09.004 · Cited by 24
A rapid juvenile murine model of nonalcoholic steatohepatitis (NASH): Chronic intermittent hypoxia exacerbates Western diet-induced NASH
Zhou, J., Zhao, Y., Guo, Y., Zhao, Y., Liu, H., Ren, J., Li, J.-R., & Ji, E. (2021) · Life Sciences · doi:10.1016/j.lfs.2021.119403 · Cited by 21
The intestinal-hepatic axis: a comprehensive review on fructose metabolism and its association with mortality and chronic metabolic diseases
Dong, Y., Li, W., & Yin, J. (2023) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2023.2253468 · Cited by 23
“These experiments also revealed that fructose catabolism in hepatocytes stimulated hepatic lipogenesis gene expression, while microorganisms metabolized fructose to produce acetyl-CoA, providing nutrients for lipid synthesis in the liver (S. Zhao et al. 2020).”
Interindividual differences in aronia juice tolerability linked to gut microbiome and metabolome changes—secondary analysis of a randomized placebo-controlled parallel intervention trial
Lackner, S., Mahnert, A., Moissl‐Eichinger, C., Madl, T., Habisch, H., Meier‐Allard, N., Kumpitsch, C., Lahousen, T., Kohlhammer-Dohr, A., Mörkl, S., et al. (2024) · Microbiome · doi:10.1186/s40168-024-01774-4 · Cited by 26
“Despite potential induction of hepatic de novo lipogenesis by high fructose ingestion and microbial fermentation of fructose to acetate in the gut [99], our study suggests to exclude the influence of fructose on lipoprotein alteration in our cohort.”
Background
Morroniside delays the progression of non-alcoholic steatohepatitis by promoting AMPK-mediated lipophagy
Zhang, C., Tong, Q., Liu, K., Mao, T., Song, Y., Qu, Y., Chen, X., & Qiu, Z. (2024) · Phytomedicine · doi:10.1016/j.phymed.2024.155703 · Cited by 20
Dietary Strategies to Modulate Gut Microbiota in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
Perazza, F., Leoni, L., Selvatici, B., Girolami, F., Bonalumi, A., Beretta, A., Ferri, S., Petroni, M. L., Piscaglia, F., Ravaioli, F., et al. (2025) · Nutrients · doi:10.3390/nu17111906 · Cited by 25
“In a paper published in Nature , authors showed that acetate is strongly connected with hepatic de novo lipogenesis, in particular, as a result of the microbial metabolism of fructose [46].”
The role of probiotics, prebiotics, and postbiotics: cellular and molecular pathways activated on glial cells in Alzheimer’s disease
Patricio-Martínez, A., Patricio, F., Macuil-Chapuli, E., Martínez-Juárez, E. Á., Flores-Díaz, S., Cedillo-Ramirez, M. L., & Limón, I. D. (2025) · Frontiers in Neuroscience · doi:10.3389/fnins.2025.1598011 · Cited by 23
Gut Microbial Genes and Metabolism for Methionine and Branched-Chain Amino Acids in Diabetic Nephropathy
Kim, J. E., Nam, H., Park, J. I., Cho, H., Lee, J., Kim, H., Kim, D. K., Joo, K. W., Kim, D. K., Kim, B. S., et al. (2023) · Microbiology Spectrum · doi:10.1128/spectrum.02344-22 · Cited by 21
“The metabolic roles of the gut microbiome have recently been recognized (24, 25), which may have effects on various disease conditions and immunoregulation (26–28).”
Background
Nutrient regulation of development and cell fate decisions
Tu, W. B., Christofk, H. R., & Plath, K. (2023) · Development · doi:10.1242/dev.199961 · Cited by 23
Fructose aggravates copper-deficiency-induced non-alcoholic fatty liver disease
Jiang, X. M., Hu, R., Huang, Y., Xu, Y., Zheng, Z., Shi, Y., Miao, J., & Liu, Y. (2023) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2023.109402 · Cited by 19
Fructose regulates the pentose phosphate pathway and induces an inflammatory and resolution phenotype in Kupffer cells
Lodge, M., Scheidemantle, G. M., Adams, V. R., Cottam, M. A., Richard, D., Breuer, D., Thompson, P. M., Shrestha, K., Liu, X., & Kennedy, A. J. (2024) · Scientific Reports · doi:10.1038/s41598-024-54272-w · Cited by 26
“Although the literature has summarized the effects of fructose on hepatocytes, it remains unknown how fructose directly impacts the function and phenotype of macrophages 31,32 .”
Background
Imaging Approaches for the Study of Metabolism in Real Time Using Genetically Encoded Reporters
Chandris, P., Giannouli, C. C., & Panayotou, G. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.725114 · Cited by 19
Hidden in the Fat: Unpacking the Metabolic Tango Between Metabolic Dysfunction-Associated Steatotic Liver Disease and Metabolic Syndrome
Boulos, M., Mousa, R. S., Jeries, N., Simaan, E., Alam, K., Bulus, B., & Assy, N. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26073448 · Cited by 22
“…beverages (SSBs), particularly those that contain fructose, which are associated with elevated DNL. Fatty acid synthase and acetyl-CoA carboxylase alpha (ACACA) (which codes for ACC1) are two genes in the DNL pathway that have been demonstrated to be upregulated by fructose consumption [247].”
Effect of different types of sugar on gut physiology and microbiota in overfed goose
Lu, C., Wei, R., Deng, D., Luo, Z. Y., Abdulai, M., Liu, H., Kang, B., Hu, S., Li, L., Xu, H., et al. (2021) · Poultry Science · doi:10.1016/j.psj.2021.101208 · Cited by 19
Inulin mitigates high fructose-induced gut dysbiosis and metabolic dysfunction in mice
Wei, S., Wang, J., Wang, C., Wang, Y., & Jin, M. (2022) · Journal of Functional Foods · doi:10.1016/j.jff.2022.105236 · Cited by 19
Excessive consumption of the sugar rich longan fruit promoted the development of nonalcoholic fatty liver disease via mediating gut dysbiosis
Huang, H., Li, M., Wang, Y., Wu, X., Wang, Q., Shen, J., Xiao, Z., 赵曰水, Du, F., Li, J., et al. (2022) · Food Frontiers · doi:10.1002/fft2.185 · Cited by 18
Metabolic reprogramming by Acly inhibition using SB-204990 alters glucoregulation and modulates molecular mechanisms associated with aging
Sola‐García, A., Cáliz‐Molina, M. Á., Espadas, I., Petr, M. A., Panadero‐Morón, C., González-Morán, D., Martín-Vázquez, M. E., Narbona‐Pérez, Á. J., López–Noriega, L., Martínez-Corrales, G., et al. (2023) · Communications Biology · doi:10.1038/s42003-023-04625-4 · Cited by 21
The role of small intestinal bacterial overgrowth in obesity and its related diseases
Yao, Q., Yu, Z., Meng, Q., Chen, J., Liu, Y., Song, W., Ren, X., Zhou, J., & Chen, X. (2023) · Biochemical Pharmacology · doi:10.1016/j.bcp.2023.115546 · Cited by 19
Fructose-induced metabolic reprogramming of cancer cells
Ting, K. K. Y. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1375461 · Cited by 21
“All ﬁ gures are created with Biorender.com. shown that microbial-derived acetate post fructose metabolism by gut-microbiota is the primary source that supplies the lipogenic pools of acetyl-CoA, a process independent of ACLY activities (13).”
Background
Type 3 Diabetes: Linking Insulin Resistance to Cognitive Decline
Chapple, B. E., Bayliss, E., Woodfin, S., Smith, M., Winter, J., & Moore, W. (2025) · Diseases · doi:10.3390/diseases13110359 · Cited by 22
“Hepatic steatosis is characterized by excess lipid accumulation and is associated with insulin resistance [157,158].”
The gut-liver axis in hepatobiliary diseases
Ichikawa, M., Okada, H., Nakamoto, N., Taniki, N., Chu, P., & Kanai∥, T. (2024) · Inflammation and Regeneration · doi:10.1186/s41232-023-00315-0 · Cited by 19
The central role of mitochondrial metabolism in hepatic steatosis
Win, S., Than, T. A., Kaplowitz, N., Wong, N., Arya, A., Win, Z. T., Win, S. H., Phyu, E., Kuemerle, C., Suh, J., et al. (2024) · Exploration of Digestive Diseases · doi:10.37349/edd.2024.00039 · Cited by 18
Are all sugars equal? Role of the food source in physiological responses to sugars with an emphasis on fruit and fruit juice
Gonzalez, J. T. (2024) · European Journal of Nutrition · doi:10.1007/s00394-024-03365-3 · Cited by 24
“However, rodent data indicate that dietary sugars may increase hepatic de novo lipogenesis via the production of acetate by the gut microbiome [71].”
Background
High dietary Fructose Drives Metabolic Dysfunction-Associated Steatotic Liver Disease via Activating ubiquitin-specific peptidase 2/11β-hydroxysteroid dehydrogenase type 1 Pathway in Mice
Li, C., Li, M., Wei, S., Zhou, W., Zhang, Z., Ji, G., & Zhang, L. (2024) · International Journal of Biological Sciences · doi:10.7150/ijbs.97309 · Cited by 25
“Within the alimentary tract, dietary fructose is swiftly assimilated through intestinal uptake and directed towards hepatic metabolism 10 .”
Background
The current findings on the gut-liver axis and the molecular basis of NAFLD/NASH associated with gut microbiome dysbiosis
Sharma, S., Tiwari, N., & Tanwar, S. S. (2025) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-025-04069-z · Cited by 24
“Depletion of gut microbiota or suppression of hepatic ACSS2 significantly reduces the conversion of fructose to hepatic acetyl-CoA and fatty acids (Zhao et al. 2020).”
ACSS2 and metabolic diseases: from lipid metabolism to therapeutic target
El-Kurjieh, A., Al-Arab, R., Hachem, Q. A., Ibrahim, J.-N., & Kobeissy, P. H. (2025) · Lipids in Health and Disease · doi:10.1186/s12944-025-02491-z · Cited by 17
“Thus, ACSS2 plays a role in DNL upon excess fructose consumption, contributing to the accumulation of triglyceride in the liver [59].”
Influential
Dietary fructose as a metabolic risk factor
Sindhunata, D. P., Meijnikman, A. S., Gerdes, V. E. A., & Nieuwdorp, M. (2022) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00439.2021 · Cited by 17
Sex Difference is a Determinant of Gut Microbes and Their Metabolites SCFAs/MCFAs in High Fat Diet Fed Rats
Shi, Y. Q., Lin, W., Lin, X., Wu, S., Yue, F., Xia, K., & Zhang, D. (2022) · Current Microbiology · doi:10.1007/s00284-022-03025-x · Cited by 19
Genetic Loss of Sucrase-Isomaltase Function: Mechanisms, Implications, and Future Perspectives
Senftleber, N. K., Ramne, S., Moltke, I., Jørgensen, M. E., Albrechtsen, A., Hansen, T. F., & Andersen, M. K. (2023) · The Application of Clinical Genetics · doi:10.2147/tacg.s401712 · Cited by 17
Opportunities and Challenges for Inhibitors Targeting Citrate Transport and Metabolism in Drug Discovery
Zhang, L., Hu, W., Qiu, Z., Li, Z., & Bian, J. (2023) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.3c00179 · Cited by 17
The fructose survival hypothesis as a mechanism for unifying the various obesity hypotheses
Johnson, R. J., Sánchez‐Lozada, L. G., & Lanaspa, M. A. (2023) · Obesity · doi:10.1002/oby.23920 · Cited by 20
“A microbiome connection is also apparent, as fructose metabolism generates acetate in the gut that helps drive lipogenesis [68].”
Background
Regulation of nutrient uptake by AMP-activated protein kinase
Alghamdi, F. B., Alshuweishi, Y., & Salt, I. P. (2020) · Cellular Signalling · doi:10.1016/j.cellsig.2020.109807 · Cited by 18
Analysis of sex differences in dietary copper-fructose interaction-induced alterations of gut microbial activity in relation to hepatic steatosis
Song, M., Yuan, F., Li, X., Ma, X., Yin, X., Rouchka, E. C., Zhang, X., Deng, Z., Prough, R. A., & McClain, C. J. (2021) · Biology of Sex Differences · doi:10.1186/s13293-020-00346-z · Cited by 17
“Second, fructose metabolism in hepatocytes activates a signal leading to lipogenic gene expression [66].”
Background
Are fat and sugar just as detrimental in old age?
Valencia, A. P., Nagaraj, N., Osman, D. H., Rabinovitch, P. S., & Marcinek, D. J. (2021) · GeroScience · doi:10.1007/s11357-021-00390-6 · Cited by 18
Is liver steatosis a disease or the emperor’s new clothes?
Krag, A. A., Tacke, F., Israelsen, M. E., & Younossi, Z. M. (2026) · Journal of Hepatology · doi:10.1016/j.jhep.2025.12.026 · Cited by 16
Suppression of uric acid and lactate production by sodium acetate ameliorates hepatic triglyceride accumulation in fructose-insulin resistant pregnant rats
Oyabambi, A. O., Olaniyi, K. S., Soladoye, A. O., & Olatunji, L. A. (2020) · Environmental Toxicology and Pharmacology · doi:10.1016/j.etap.2020.103452 · Cited by 16
Dramatic Suppression of Lipogenesis and No Increase in Beta-Oxidation Gene Expression Are among the Key Effects of Bergamot Flavonoids in Fatty Liver Disease
Parafati, M., Russa, D. L., Lascala, A., Crupi, F., Riillo, C., Fotschki, B., Mollace, V., & Janda, E. (2024) · Antioxidants · doi:10.3390/antiox13070766 · Cited by 16
“Most lipogenic enzymes are upregulated in high-fat diet [23–25], fructose or sucrose [22,26,27] or Western diet-induced [28] animal models of NAFLD and NASH, but their differential expression has never been investigated in CAF diet compared to normal diet livers.”
Background
The short-chain fatty acid acetate modulates epithelial-to-mesenchymal transition
Lyu, J., Pirooznia, M., Li, Y., & Xiong, J. (2022) · Molecular Biology of the Cell · doi:10.1091/mbc.e22-02-0066 · Cited by 16
Integrative microbiome and metabolome profiles reveal the impacts of periodontitis via oral-gut axis in first-trimester pregnant women
Cheng, T., Wen, P., Yu, R., Zhang, F., Li, H., Xu, X., Zhao, D., Liu, F., Su, W., Zheng, Z., et al. (2024) · Journal of Translational Medicine · doi:10.1186/s12967-024-05579-9 · Cited by 18
“…no hypertension case in our study, Coprococcus positively links to Perio-associated triglyceride, CRP, and fasting blood glucose, echoing that Coprococcus member links to serum metabolic and corpulence traits as well as clinical comorbidities [38, 39], possibly due to fructose-induced obesity [40].”
Background
Disruption of hindgut microbiome homeostasis promotes postpartum energy metabolism disorders in dairy ruminants by inhibiting acetate-mediated hepatic AMPK-PPARA axis
Wang, S., Kong, F., Zhang, X., Dai, D., Li, C., Cao, Z., Wang, Y., Wang, W., & Li, S. (2025) · Microbiome · doi:10.1186/s40168-025-02150-6 · Cited by 17
“Zhao et al . demonstrated that fructose intake increased the concentration of acetic acid in the gut of mice, thereby promoting hepatic fat deposition [61].”
Gut microbiome in liver pathophysiology and cholestatic liver disease
Yan, S., & Yin, X. (2021) · Liver Research · doi:10.1016/j.livres.2021.08.001 · Cited by 16
Gut microbiota and related metabolites in the pathogenesis of nonalcoholic steatohepatitis and its resolution after bariatric surgery
Martínez‐Montoro, J. I., Kuchay, M. S., Román, A. B., Martínez‐Sánchez, M. A., Frutos, M. D., Fernández‐García, J. C., & Ramos‐Molina, B. (2021) · Obesity Reviews · doi:10.1111/obr.13367 · Cited by 16
Yiqi-Bushen-Tiaozhi Recipe Attenuated High-Fat and High-Fructose Diet Induced Nonalcoholic Steatohepatitis in Mice via Gut Microbiota
Yan, J., Nie, Y., Liu, Y., Li, J., Wu, L., Chen, Z., & He, B. (2022) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2022.824597 · Cited by 15
“have confirmed that ingested fructose affects hepatic fat accumulation and NAFLD/NASH progression through the gut microbiota (Zhao et al., 2020).”
Background
Association of sugar-sweetened beverages with the risk of colorectal cancer: a systematic review and meta-analysis
Feng, L., Gao, J., Xia, W., Li, Y., Lowe, S., Yau, V., Ma, S., Zhou, Z., Ding, P., Cheng, C., et al. (2023) · European Journal of Clinical Nutrition · doi:10.1038/s41430-023-01302-x · Cited by 19
“The future studies should further consider examining the linear relationship between greater intake of sugar-sweetened beverages and CRC.”
Background
Hyperacetylated histone H4 is a source of carbon contributing to lipid synthesis
Charidemou, E., Noberini, R., Ghirardi, C., Georgiou, P., Marcou, P., Theophanous, A., Strati, K., Keun, H. C., Behrends, V., Bonaldi, T., et al. (2024) · The EMBO Journal · doi:10.1038/s44318-024-00053-0 · Cited by 15
“It was previously demonstrated that ACSS2 can signi ﬁ cantly contribute to lipogenic acetyl-CoA independently of ACLY (Zhao et al, 2020).”
BackgroundInfluential
The role of amino acid metabolism in autoimmune hepatitis
Xiang, X., Li, Q., Wan, J., Chen, C., Guo, M., He, Z., Wang, D., Zhao, X., & Xu, L. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.116452 · Cited by 15
Nucleoside diphosphate kinases 1 and 2 regulate a protective liver response to a high-fat diet
Iuso, D., Garcia-Saez, I., Couté, Y., Yamaryo-Botté, Y., Boeri Erba, E., Adrait, A., Zeaiter, N., Tokarska-Schlattner, M., Jilkova, Z. M., Boussouar, F., et al. (2023) · Science Advances · doi:10.1126/sciadv.adh0140 · Cited by 14
Mindful Eating: A Deep Insight Into Fructose Metabolism and Its Effects on Appetite Regulation and Brain Function
Monar, G. V. F., Cruz, C. S., & Martinez, E. C. (2025) · Journal of Nutrition and Metabolism · doi:10.1155/jnme/5571686 · Cited by 14
“In such scenarios, excess fructose that reaches the liver contributes to fat formation, while fructose catabolized by gut microbiota induces alterations in composition and dysbiosis [47, 48].”
The enedioic acid analog 326E alleviates metabolic dysfunction-associated steatohepatitis via dual targeting at ACLY and PPARα
Xie, Z., Cheng, L., Hu, Y. H., Song, G., Wang, F., Zhang, M., Zhang, Y., Zhang, X., Zhou, C., Zhu, X., et al. (2025) · Cell Metabolism · doi:10.1016/j.cmet.2025.09.011 · Cited by 14
The many pathways driving liver inflammation in MASH
Tilg, H., Adolph, T. E., Romeo, S., & Loomba, R. S. (2026) · Cell Metabolism · doi:10.1016/j.cmet.2026.02.018 · Cited by 17
Gut microbiota, determined by dietary nutrients, drive modification of the plasma lipid profile and insulin resistance
Watanabe, Y., Fujisaka, S., Ikeda, K., Ishikawa, M., Yamada, T., Nawaz, A., Kado, T., Kuwano, T., Nishimura, A., Bilal, M., et al. (2021) · iScience · doi:10.1016/j.isci.2021.102445 · Cited by 15
Self-citation
Global Microbiota‐Dependent Histone Acetylation Patterns Are Irreversible and Independent of Short Chain Fatty Acids
Saiman, Y., Shen, T. D., Lund, P. J., Gershuni, V. M., Jang, C., Patel, S., Jung, S., Furth, E. E., Friedman, E. S., Chau, L., et al. (2021) · Hepatology · doi:10.1002/hep.32043 · Cited by 15
Self-citation
A diet high in FODMAPs as a novel dietary strategy in diabetes?
Chu, N. H. S., Chan, J. C. N., & Chow, E. (2022) · Clinical Nutrition · doi:10.1016/j.clnu.2022.07.036 · Cited by 15
Interaction mechanism and intervention strategy between metabolic dysfunction-associated steatotic liver disease and intestinal microbiota
Yang, W., Jin, Q., Xiao, D., Li, X., & Huang, D. (2025) · Frontiers in Microbiology · doi:10.3389/fmicb.2025.1597995 · Cited by 13
Novel insights in intestinal and hepatic fructose metabolism: from mice to men
Koene, E., Schrauwen‐Hinderling, V. B., Schrauwen, P., & Brouwers, M. C. G. J. (2022) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0000000000000853 · Cited by 13
“[9] assigned another function to the gut microbiome.”
Background
Some paradoxes and unresolved aspects of hepatic de novo lipogenesis
Jones, J. G. (2024) · npj Metabolic Health and Disease · doi:10.1038/s44324-024-00020-7 · Cited by 14
“Finally, in the case of fructose,thereisevidencethatasigni ﬁ cantfractionismetabolizedtoglucose and short-chain fatty acids in the intestine 34 .”
Skeletal muscle insulin resistance and adipose tissue hypertrophy persist beyond the reshaping of gut microbiota in young rats fed a fructose-rich diet
Mazzoli, A., Porzio, A. D., Gatto, C., Crescenzo, R., Nazzaro, M., Spagnuolo, M. S., Baccigalupi, L., Ricca, E., Amoresano, A., Fontanarosa, C., et al. (2022) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2022.109247 · Cited by 14
Host and microbiome lipid metabolism in colorectal cancer development and therapy
Evora, G. M., Brauer, M., & Letellier, E. (2025) · Trends in cancer · doi:10.1016/j.trecan.2025.08.005 · Cited by 17
Liver-breast communication of adipocyte-oriented exosomes drives primary mammary cancer progression
Li, C., Lu, Y., Li, Y., Liu, T., Deng, H. X., Gao, M., Zhou, B., Liu, J., Cai, J., Huang, D., et al. (2025) · Cell Metabolism · doi:10.1016/j.cmet.2025.08.012 · Cited by 14
Self-citation
sSTEAP4 regulates cellular homeostasis and improves high-fat-diet-caused oxidative stress in hepatocytes
Zhu, L., Li, B., Chen, D., Chen, N., Xu, L., Zhao, L., & Chen, X. (2022) · Life Sciences · doi:10.1016/j.lfs.2022.120438 · Cited by 12
The Intersection of Genetic Factors, Aberrant Nutrient Metabolism and Oxidative Stress in the Progression of Cardiometabolic Disease
Butcko, A. J., Putman, A. K., & Mottillo, E. P. (2024) · Antioxidants · doi:10.3390/antiox13010087 · Cited by 12
“…generates acetate to feed hepatic DNL, independent of ATP-citrate lyase (ACLY), the rate limiting enzyme for conversion of citrate to acetyl-CoA [62]. dual mechanism of substrate ﬂ ux and upregulation of These data likely explain a dual mechanism of substrate flux and upregulation of DNL…”
BackgroundInfluential
The Influence of Diet and Its Components on the Development and Prevention of Hepatocellular Carcinoma (HCC)
Janota, B., & Szymanek, B. (2024) · Cancers · doi:10.3390/cancers16051030 · Cited by 13
“These errors, accompanying the development of visceral obesity and dyslipidemia, result in insulin resistance and the stimulation of de novo lipogenesis in the liver [12,13].”
Background
Pomegranate supplementation alleviates dyslipidemia and the onset of non-alcoholic fatty liver disease in Wistar rats by shifting microbiota and producing urolithin-like microbial metabolites
Sánchez-Terrón, G., Martínez, R., Morcuende, D., Caballero, V., & Estévez, M. (2024) · Food & Function · doi:10.1039/d4fo00688g · Cited by 13
Lipidome is lipids regulator in gastrointestinal tract and it is a life collar in COVID-19: A review
Koriem, K. M. M. (2020) · World Journal of Gastroenterology · doi:10.3748/wjg.v27.i1.37 · Cited by 12
Interventions for non-alcoholic liver disease: a gut microbial metabolites perspective
Guo, J., Shi, C., Zhang, Q., Deng, W., Zhang, L., Chen, Q., Zhang, D., & Gong, Z. (2022) · Therapeutic Advances in Gastroenterology · doi:10.1177/17562848221138676 · Cited by 14
Microbial Interactions with Intestinal Lipid Digestion and Absorption: Emerging Targets for Metabolic Disorders
Yin, J., Zhang, M., Jiang, W., Huang, X., & Yin, Y. (2025) · Research · doi:10.34133/research.0904 · Cited by 15
“Dietary fructose increases intestinal villus length in the duodenum and proximal jejunum by 25% to 40%, correlating with enhanced lipid absorption and accelerated obesity through modulation of the gut microbiome [ 42 , 115 ].”
Immunotherapy resistance in MASLD-related hepatocellular carcinoma: special immune microenvironment and gut microbiota
Jin, J., Cheng, K., Chen, M., Liang, H., & Zhang, W. (2025) · International Journal of Biological Sciences · doi:10.7150/ijbs.117394 · Cited by 13
“SCFAs, including butyrate, propionate, and acetate, are enriched in MASLD-HCC patients and drive MASLD progression by regulating hepatic lipogenesis [198-202].”
Fructose: metabolic signal and modern hazard
Johnson, R. J., Lanaspa, M. A., Tolan, D. R., Goncalves, M. D., Softic, S., Stanhope, K. L., Sánchez‐Lozada, L. G., Herman, M. A., & Rabinowitz, J. D. (2026) · Nature Metabolism · doi:10.1038/s42255-026-01506-y · Cited by 13
“Excess fructose intake can also lead to passage of fructose to the colon, where it can be metabolized to acetate, which subsequently can reach the portal vein and liver, to be converted to acetyl-CoA and fat 41 .”
Self-citation
LncRNA Nron deficiency protects mice from diet-induced adiposity and hepatic steatosis
Liu, B., Zhong, Y., Huang, D., Yang, L., Wang, P., Liu, Y., Zhang, F., Li, X., Liang, M., Huang, K., et al. (2023) · Metabolism · doi:10.1016/j.metabol.2023.155609 · Cited by 11
The glucose-to-acetate metabolic flux that drives endothelial-to-mesenchymal transition via TGF-β signaling
Recatalá, C. A., & Santoro, M. M. (2023) · Cell Metabolism · doi:10.1016/j.cmet.2023.06.006 · Cited by 11
Gut microbes, diet, and genetics as drivers of metabolic liver disease: a narrative review outlining implications for precision medicine
Hermanson, J. B., Tolba, S. A., Chrisler, E. A., & Leone, V. (2024) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2024.109704 · Cited by 12
Fructose induces inflammatory activation in macrophages and microglia through the nutrient‐sensing ghrelin receptor
Shen, Z., Liu, Z., Wang, H., Landrock, D., Noh, J. Y., Zang, Q. S., Lee, C., Farnell, Y. Z., Chen, Z., & Sun, Y. (2025) · The FASEB Journal · doi:10.1096/fj.202402531r · Cited by 11
“18,41,42 The RT-qPCR results revealed a significantly elevated expression of the pro-inflammatory polarization signature gene iNOS and pro-inflammatory cytokine genes of Tnfa , Il1b , and Il6 in both RAW 264.7 and IMG cells with fructose exposure ( + Fru) (Figure 1B,C).”
Influential
All Fiber is Not Fiber
Rahman, S., Trone, K. E., Kelly, C. J., Stroud, A., & Martindale, R. G. (2022) · Current Gastroenterology Reports · doi:10.1007/s11894-022-00858-1 · Cited by 13
“Finally, high dietary fructose intake can increase the microbial-generated acetate substantially [96, 97].”
Background
Combined Inhibition of UBE2C and PLK1 Reduce Cell Proliferation and Arrest Cell Cycle by Affecting ACLY in Pan-Cancer
Liang, K., Wang, Q., Qiu, L., Gong, X., Chen, Z., Zhang, H., Ding, K., Liu, Y., Wei, J., Lin, S., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242115658 · Cited by 12
“The inhibition of ACLY can be bypassed in some cancer cells [98] and in the livers of mice fed a high-fructose diet [96] through the upregulation of ACSS2.”
Background
Roles of short-chain fatty acids in metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction-associated steatohepatitis
Zhang, C., Liu, S., Sui, Y., & Yang, M. J. (2025) · World Journal of Hepatology · doi:10.4254/wjh.v17.i11.113756 · Cited by 14
Added sugars, gut microbiota, and host health
Zhang, Y., Walker, R. W., Kaplan, R. C., & Qi, Q. (2025) · Gut Microbes · doi:10.1080/19490976.2025.2592431 · Cited by 12
“…of triose-phosphate intermediates fuelling de novo lipogenesis, 115 upregulation of transcriptional regulators such as carbohydrate-responsive element-binding protein (ChREBP) and sterol regulatory element-binding protein-1c (SREBP-1c), 115 and gut microbiota-related bile acid metabolism.”
Influential
Intracellular spatiotemporal metabolism in connection to target engagement
Zhang, J., Qiu, Z., Zhang, Y. J., Wang, G., & Hao, H. (2023) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2023.115024 · Cited by 10
Fucoidan, as a marine bioactive substance, has shown great potential in regulating the bone-gut axis
Zhao, Z., Sun, H., Fu, Y., Liang, X., Fan, T., Li, X., Zhu, L., Xu, L., Wang, X., Li, J., et al. (2023) · Algal Research · doi:10.1016/j.algal.2023.103323 · Cited by 10
Fructose induces hepatic steatosis in adolescent mice linked to the disorders of lipid metabolism, bile acid metabolism, and autophagy
Deng, S., Ge, Y., Zhai, Z., Liu, H., Zhang, X., Chen, Y., Yang, Y., & Wu, Z. (2024) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2024.109635 · Cited by 10
The Effects of Long-Term High Fat and/or High Sugar Feeding on Sources of Postprandial Hepatic Glycogen and Triglyceride Synthesis in Mice
Reis-Costa, A., Belew, G. D., Viegas, I., Tavares, L. C., Meneses, M. J., Patrício, B. G., Gastaldelli, A., Macedo, M. P., & Jones, J. G. (2024) · Nutrients · doi:10.3390/nu16142186 · Cited by 13
“It is not known what fraction of this fructose underwent PP oxidation prior to lactate formation.”
Background
Acetyl-CoA synthesis in the skin is a key determinant of systemic lipid homeostasis
Nguyen, P. T., Shiue, M., Kuprasertkul, N., Costa‐Pinheiro, P., Izzo, L., Pinheiro, L. V., Affronti, H. C., Gugiu, G. B., Ghaisas, S., Liu, J. Y., et al. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.115284 · Cited by 12
“27 Hence, genetic studies of ACLY have been limited to cell-or tissue-specific knockouts (e.g., in adipose tissues, 28–30 liver, 31–34 pancreas, 14 myeloid cells, 35–37 and T cells 38,39 ).”
Self-citation
Murine gut microbial interactions exert antihyperglycemic effects
Guo, L., Xu, L., Nie, Y., Liu, L., Liu, Z., & Yang, Y. (2025) · The ISME Journal · doi:10.1093/ismejo/wraf028 · Cited by 10
“Second, the gut microbiota regulates glucose and lipid metabolism by synthesizing functional metabolites [12–15].”
Targeted Sodium Acetate Liposomes for Hepatocytes and Kupffer Cells: An Oral Dual-Targeted Therapeutic Approach for Non-Alcoholic Fatty Liver Disease Alleviation
Hou, Y., Gao, X., Gong, J., Dong, X., Hao, Y., Zhai, Z., Zhang, H., Zhang, M., Liu, R., Wang, R., et al. (2025) · Nutrients · doi:10.3390/nu17050930 · Cited by 12
“In addition to being energy substrates, SCFAs are also signaling molecules, which influences the development of NAFLD [6].”
Influential
KRAS G12V mutation-selective requirement for ACSS2 in colorectal adenoma formation
Budagyan, K., Cannon, A. C., Chatoff, A. G., Benton, D., Kurimchak, A., Araiza‐Olivera, D., Gerasimova, A., Snyder, N. W., Duncan, J. S., Uribe‐Alvarez, C., et al. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.115444 · Cited by 11
“39 In this study, we found that KRAS G12V mutants exhibited greater acetate incorporation into cytoplasmic acetyl-CoAs, and that Acss2 KO significantly affected the ability of KRAS G12V mutants to generate cholesterol esters but had no effect on other mutants.”
Self-citation
Pediatric nonalcoholic fatty liver disease and the microbiome: Mechanisms contributing to pathogenesis and progression
Salzman, N. H., & Schwimmer, J. B. (2021) · Current Opinion in Endocrine and Metabolic Research · doi:10.1016/j.coemr.2021.05.003 · Cited by 11
Fructose, glucose and fat interrelationships with metabolic pathway regulation and effects on the gut microbiota
Szabó, J., Maróti, G., Solymosi, N., Andrásofszky, E., Tuboly, T., Bersényi, A., Bruckner, G. G., & Hullár, I. (2021) · Acta Veterinaria Hungarica · doi:10.1556/004.2021.00022 · Cited by 10

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: Zhao, Steven
Jang, Cholsoon
Liu, Joyce
Uehara, Kahealani
Gilbert, Michael
Izzo, Luke
Zeng, Xianfeng
Trefely, Sophie
Carrer, Alessandro
Miller, Katelyn D.
Schug, Zachary T.
Snyder, Nathaniel W.
Gade, Terence P.
Titchenell, Paul M.
Rabinowitz, Joshua D.
Wellen, Kathryn E.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2020-03-18
Volume: 579
Issue: 7800
Pages: 586-591
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/s41586-020-2101-7
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
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
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

Dietary fructose feeds hepatic lipogenesis via microbiota-derived acetate

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks