CoChat
Sign Up
Cited by 75Fibroblast Growth Factor ResearchLiver Disease Diagnosis and TreatmentLiver physiology and pathology

FGF21 reverses MASH through coordinated actions on the CNS and liver

Open access
Rose, Jesse P., Morgan, Donald A., Sullivan, Andrew I., Fu, Xiaorong, Inigo-Vollmer, Melissa, Burgess, Shawn C., Meyerholz, David K., Rahmouni, Kamal +1 more·2025·Cell Metabolism
DOI 10.1016/j.cmet.2025.04.014PMC PMC12409791
Open this paper in CoChat — free account

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form, metabolic dysfunction-associated steatohepatitis (MASH), represent a growing public health burden with limited therapeutic options. Recent studies have revealed that fibroblast growth factor 21 (FGF21)-based analogs can significantly improve MASH, but the mechanisms for this effect are not well understood. Here, we demonstrate that the beneficial metabolic effects of FGF21 to reverse MASH are mediated through distinct mechanisms to independently lower hepatic triglyceride and cholesterol levels. Specifically, FGF21 signaling directly to glutamatergic neurons in the central nervous system (CNS) stimulates hepatic triglyceride reduction and reversal of fibrosis, whereas FGF21 signaling directly to hepatocytes is necessary and sufficient to reduce hepatic cholesterol levels in mice. Mechanistically, we show that FGF21 acts in the CNS to increase sympathetic nerve activity to the liver, which suppresses hepatic de novo lipogenesis. These results provide critical insights into a promising pharmacological target to treat MASH.

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.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.cmet.2025.04.014

Cites

27 of 27 references verified0 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.

A few free checks a day · papers already verified open instantly · results are public

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.

Cites

Flagged first, then by citations

Research works printed but not linked: 67

  1. [2]Younossi ZM, Kalligeros M, and Henry L (2024). Epidemiology of Metabolic Dysfunction-Associated Steatotic Liver Disease. Clin Mol Hepatol. 10.3350/cmh.2024.0431. PMC11925440 39159948 · DOI · Paper page
  2. [4]Younossi ZM, Tampi R, Priyadarshini M, Nader F, Younossi IM, and Racila A (2019). Burden of Illness and Economic Model for Patients With Nonalcoholic Steatohepatitis in the United States. Hepatology 69, 564– 572. 10.1002/hep.30254. 30180285 · DOI
  3. [6]Flippo KH, and Potthoff MJ (2021). Metabolic Messengers: FGF21. Nat Metab 3, 309– 317. 10.1038/s42255-021-00354-2. 33758421 PMC8620721 · DOI · Paper page
  4. [7]Chen L, Fu L, Sun J, Huang Z, Fang M, Zinkle A, Liu X, Lu J, Pan Z, Wang Y, (2023). Structural basis for FGF hormone signalling. Nature 618, 862– 870. 10.1038/s41586-023-06155-9. 37286607 PMC10284700 · DOI
  5. [10]Ogawa Y, Kurosu H, Yamamoto M, Nandi A, Rosenblatt KP, Goetz R, Eliseenkova AV, Mohammadi M, and Kuro-o M (2007). BetaKlotho is required for metabolic activity of fibroblast growth factor 21. Proc Natl Acad Sci U S A 104, 7432– 7437. 10.1073/pnas.0701600104. 17452648 PMC1855074 · DOI · Paper page
  6. [13]Ding X, Boney-Montoya J, Owen BM, Bookout AL, Coate KC, Mangelsdorf DJ, and Kliewer SA (2012). betaKlotho is required for fibroblast growth factor 21 effects on growth and metabolism. Cell Metab 16, 387– 393. 10.1016/j.cmet.2012.08.002. 22958921 PMC3447537 · DOI · Paper page
  7. [14]BonDurant LD, Ameka M, Naber MC, Markan KR, Idiga SO, Acevedo MR, Walsh SA, Ornitz DM, and Potthoff MJ (2017). FGF21 Regulates Metabolism Through Adipose-Dependent and -Independent Mechanisms. Cell Metab 25, 935– 944 e934. 10.1016/j.cmet.2017.03.005. 28380381 PMC5494834 · DOI · Paper page
  8. [15]Holland WL, Adams AC, Brozinick JT, Bui HH, Miyauchi Y, Kusminski CM, Bauer SM, Wade M, Singhal E, Cheng CC, (2013). An FGF21-adiponectinceramide axis controls energy expenditure and insulin action in mice. Cell Metab 17, 790– 797. 10.1016/j.cmet.2013.03.019. 23663742 PMC3667496 · DOI
  9. [16]Flippo KH, Jensen-Cody SO, Claflin KE, and Potthoff MJ (2020). FGF21 signaling in glutamatergic neurons is required for weight loss associated with dietary protein dilution. Sci Rep 10, 19521. 10.1038/s41598-020-76593-2. 33177640 PMC7658965 · DOI · Paper page
  10. [17]Claflin KE, Sullivan AI, Naber MC, Flippo KH, Morgan DA, Neff TJ, Jensen-Cody SO, Zhu Z, Zingman LV, Rahmouni K, and Potthoff MJ (2022). Pharmacological FGF21 signals to glutamatergic neurons to enhance leptin action and lower body weight during obesity. Mol Metab 64, 101564. 10.1016/j.molmet.2022.101564. 35944896 PMC9403559 · DOI
  11. [18]Le TDV, Fathi P, Watters AB, Ellis BJ, Besing GK, Bozadjieva-Kramer N, Perez MB, Sullivan AI, Rose JP, Baggio LL, (2023). Fibroblast growth factor-21 is required for weight loss induced by the glucagon-like peptide-1 receptor agonist liraglutide in male mice fed high carbohydrate diets. Mol Metab 72, 101718. 10.1016/j.molmet.2023.101718. 37030441 PMC10131131 · DOI
  12. [19]Dushay J, Chui PC, Gopalakrishnan GS, Varela-Rey M, Crawley M, Fisher FM, Badman MK, Martinez-Chantar ML, and Maratos-Flier E (2010). Increased fibroblast growth factor 21 in obesity and nonalcoholic fatty liver disease. Gastroenterology 139, 456– 463. 10.1053/j.gastro.2010.04.054. 20451522 PMC4862867 · DOI · Paper page
  13. [20]Li H, Fang Q, Gao F, Fan J, Zhou J, Wang X, Zhang H, Pan X, Bao Y, Xiang K, (2010). Fibroblast growth factor 21 levels are increased in nonalcoholic fatty liver disease patients and are correlated with hepatic triglyceride. J Hepatol 53, 934– 940. 10.1016/j.jhep.2010.05.018. 20675007 · DOI
  14. [21]Yilmaz Y, Eren F, Yonal O, Kurt R, Aktas B, Celikel CA, Ozdogan O, Imeryuz N, Kalayci C, and Avsar E (2010). Increased serum FGF21 levels in patients with nonalcoholic fatty liver disease. Eur J Clin Invest 40, 887– 892. 10.1111/j.1365-2362.2010.02338.x. 20624171 · DOI
  15. [22]Barb D, Bril F, Kalavalapalli S, and Cusi K (2019). Plasma Fibroblast Growth Factor 21 Is Associated With Severity of Nonalcoholic Steatohepatitis in Patients With Obesity and Type 2 Diabetes. J Clin Endocrinol Metab 104, 3327– 3336. 10.1210/jc.2018-02414. 30848827 PMC7453039 · DOI
  16. [25]Tanaka N, Takahashi S, Zhang Y, Krausz KW, Smith PB, Patterson AD, and Gonzalez FJ (2015). Role of fibroblast growth factor 21 in the early stage of NASH induced by methionine- and choline-deficient diet. Biochim Biophys Acta 1852, 1242– 1252. 10.1016/j.bbadis.2015.02.012. 25736301 PMC4433820 · DOI
  17. [27]Geng L, Lam KSL, and Xu A (2020). The therapeutic potential of FGF21 in metabolic diseases: from bench to clinic. Nat Rev Endocrinol 16, 654– 667. 10.1038/s41574-020-0386-0. 32764725 · DOI · Paper page
  18. [28]Harrison SA, Rolph T, Knott M, and Dubourg J (2024). FGF21 agonists: An emerging therapeutic for metabolic dysfunction-associated steatohepatitis and beyond. J Hepatol 81, 562– 576. 10.1016/j.jhep.2024.04.034. 38710230 · DOI
  19. [29]Harrison SA, Frias JP, Neff G, Abrams GA, Lucas KJ, Sanchez W, Gogia S, Sheikh MY, Behling C, Bedossa P, (2023). Safety and efficacy of once-weekly efruxifermin versus placebo in non-alcoholic steatohepatitis (HARMONY): a multicentre, randomised, double-blind, placebo-controlled, phase 2b trial. Lancet Gastroenterol Hepatol 8, 1080– 1093. 10.1016/S2468-1253(23)00272-8. 37802088 · DOI · Paper page
  20. [32]Vacca M, Kamzolas I, Harder LM, Oakley F, Trautwein C, Hatting M, Ross T, Bernardo B, Oldenburger A, Hjuler ST, (2024). An unbiased ranking of murine dietary models based on their proximity to human metabolic dysfunction-associated steatotic liver disease (MASLD). Nat Metab 6, 1178– 1196. 10.1038/s42255-024-01043-6. 38867022 PMC11199145 · DOI · Paper page
  21. [34]Gallage S, Avila JEB, Ramadori P, Focaccia E, Rahbari M, Ali A, Malek NP, Anstee QM, and Heikenwalder M (2022). A researcher’s guide to preclinical mouse NASH models. Nat Metab 4, 1632– 1649. 10.1038/s42255-022-00700-y. 36539621 · DOI
  22. [37]Xu J, Lloyd DJ, Hale C, Stanislaus S, Chen M, Sivits G, Vonderfecht S, Hecht R, Li YS, Lindberg RA, (2009). Fibroblast growth factor 21 reverses hepatic steatosis, increases energy expenditure, and improves insulin sensitivity in diet-induced obese mice. Diabetes 58, 250– 259. 10.2337/db08-0392. 18840786 PMC2606881 · DOI · Paper page
  23. [38]Liang W, Menke AL, Driessen A, Koek GH, Lindeman JH, Stoop R, Havekes LM, Kleemann R, and van den Hoek AM (2014). Establishment of a general NAFLD scoring system for rodent models and comparison to human liver pathology. PLoS One 9, e115922. 10.1371/journal.pone.0115922. 25535951 PMC4275274 · DOI
  24. [39]Meyerholz DK, and Beck AP (2018). Principles and approaches for reproducible scoring of tissue stains in research. Lab Invest 98, 844– 855. 10.1038/s41374-018-0057-0. 29849125 · DOI
  25. [41]Bozadjieva-Kramer N, Shin JH, Li Z, Rupp AC, Miller N, Kernodle S, Lanthier N, Henry P, Seshadri N, Myronovych A, (2024). Intestinal FGF15 regulates bile acid and cholesterol metabolism but not glucose and energy balance. JCI Insight 9. 10.1172/jci.insight.174164. PMC11128213 38587078 · DOI
  26. [42]Wu X, Ge H, Lemon B, Vonderfecht S, Weiszmann J, Hecht R, Gupte J, Hager T, Wang Z, Lindberg R, and Li Y (2010). FGF19-induced hepatocyte proliferation is mediated through FGFR4 activation. J Biol Chem 285, 5165– 5170. 10.1074/jbc.M109.068783. 20018895 PMC2820743 · DOI
  27. [44]Sullivan AI, Jensen-Cody SO, Claflin KE, Vorhies KE, Flippo KH, and Potthoff MJ (2024). Characterization of FGF21 Sites of Production and Signaling in Mice. Endocrinology 165. 10.1210/endocr/bqae120. 39253796 · DOI
  28. [45]Huang X, Yu C, Jin C, Kobayashi M, Bowles CA, Wang F, and McKeehan WL (2006). Ectopic activity of fibroblast growth factor receptor 1 in hepatocytes accelerates hepatocarcinogenesis by driving proliferation and vascular endothelial growth factor-induced angiogenesis. Cancer Res 66, 1481– 1490. 10.1158/0008-5472.CAN-05-2412. 16452204 · DOI
  29. [46]Halpern KB, Shenhav R, Matcovitch-Natan O, Toth B, Lemze D, Golan M, Massasa EE, Baydatch S, Landen S, Moor AE, (2017). Single-cell spatial reconstruction reveals global division of labour in the mammalian liver. Nature 542, 352– 356. 10.1038/nature21065. 28166538 PMC5321580 · DOI · Paper page
  30. [47]MacParland SA, Liu JC, Ma XZ, Innes BT, Bartczak AM, Gage BK, Manuel J, Khuu N, Echeverri J, Linares I, (2018). Single cell RNA sequencing of human liver reveals distinct intrahepatic macrophage populations. Nat Commun 9, 4383. 10.1038/s41467-018-06318-7. 30348985 PMC6197289 · DOI · Paper page
  31. [48]Nault R, Fader KA, Bhattacharya S, and Zacharewski TR (2021). Single-Nuclei RNA Sequencing Assessment of the Hepatic Effects of 2,3,7,8-Tetrachlorodibenzo-p-dioxin. Cell Mol Gastroenterol Hepatol 11, 147– 159. 10.1016/j.jcmgh.2020.07.012. 32791302 PMC7674514 · DOI
  32. [50]Xiong X, Kuang H, Ansari S, Liu T, Gong J, Wang S, Zhao XY, Ji Y, Li C, Guo L, (2019). Landscape of Intercellular Crosstalk in Healthy and NASH Liver Revealed by Single-Cell Secretome Gene Analysis. Mol Cell 75, 644– 660 e645. 10.1016/j.molcel.2019.07.028. 31398325 PMC7262680 · DOI · Paper page
  33. [51]Yang C, Jin C, Li X, Wang F, McKeehan WL, and Luo Y (2012). Differential specificity of endocrine FGF19 and FGF21 to FGFR1 and FGFR4 in complex with KLB. PLoS One 7, e33870. 10.1371/journal.pone.0033870. 22442730 PMC3307775 · DOI
  34. [52]Flippo KH, Trammell SAJ, Gillum MP, Aklan I, Perez MB, Yavuz Y, Smith NK, Jensen-Cody SO, Zhou B, Claflin KE, (2022). FGF21 suppresses alcohol consumption through an amygdalo-striatal circuit. Cell Metab 34, 317– 328 e316. 10.1016/j.cmet.2021.12.024. 35108517 PMC9093612 · DOI
  35. [53]Pan J, Parlee SD, Brunel FM, Li P, Lu W, Perez-Tilve D, Liu F, Finan B, Kharitonenkov A, and DiMarchi RD (2020). Optimization of Peptide Inhibitors of beta-Klotho as Antagonists of Fibroblast Growth Factors 19 and 21. ACS Pharmacol Transl Sci 3, 978– 986. 10.1021/acsptsci.0c00100. 33073195 PMC7551714 · DOI
  36. [55]Lin Z, Tian H, Lam KS, Lin S, Hoo RC, Konishi M, Itoh N, Wang Y, Bornstein SR, Xu A, and Li X (2013). Adiponectin mediates the metabolic effects of FGF21 on glucose homeostasis and insulin sensitivity in mice. Cell Metab 17, 779– 789. 10.1016/j.cmet.2013.04.005. 23663741 · DOI · Paper page
  37. [57]Wang J, Mitsche MA, Lutjohann D, Cohen JC, Xie XS, and Hobbs HH (2015). Relative roles of ABCG5/ABCG8 in liver and intestine. J Lipid Res 56, 319– 330. 10.1194/jlr.M054544. 25378657 PMC4306686 · DOI
  38. [58]Yu L, Hammer RE, Li-Hawkins J, Von Bergmann K, Lutjohann D, Cohen JC, and Hobbs HH (2002). Disruption of Abcg5 and Abcg8 in mice reveals their crucial role in biliary cholesterol secretion. Proc Natl Acad Sci U S A 99, 16237– 16242. 10.1073/pnas.252582399. 12444248 PMC138595 · DOI
  39. [59]Patel SB, Graf GA, and Temel RE (2018). ABCG5 and ABCG8: more than a defense against xenosterols. J Lipid Res 59, 1103– 1113. 10.1194/jlr.R084244. 29728459 PMC6027916 · DOI
  40. [61]Chan KY, Jang MJ, Yoo BB, Greenbaum A, Ravi N, Wu WL, Sanchez-Guardado L, Lois C, Mazmanian SK, Deverman BE, and Gradinaru V (2017). Engineered AAVs for efficient noninvasive gene delivery to the central and peripheral nervous systems. Nat Neurosci 20, 1172– 1179. 10.1038/nn.4593. 28671695 PMC5529245 · DOI · Paper page
  41. [62]Hurr C, Simonyan H, Morgan DA, Rahmouni K, and Young CN (2019). Liver sympathetic denervation reverses obesity-induced hepatic steatosis. J Physiol 597, 4565– 4580. 10.1113/JP277994. 31278754 PMC6716997 · DOI
  42. [63]Bruinstroop E, Eliveld J, Foppen E, Busker S, Ackermans MT, Fliers E, and Kalsbeek A (2015). Hepatic denervation and dyslipidemia in obese Zucker (fa/fa) rats. Int J Obes (Lond) 39, 1655– 1658. 10.1038/ijo.2015.122. 26134416 · DOI
  43. [64]Keinicke H, Sun G, Mentzel CMJ, Fredholm M, John LM, Andersen B, Raun K, and Kjaergaard M (2020). FGF21 regulates hepatic metabolic pathways to improve steatosis and inflammation. Endocr Connect 9, 755– 768. 10.1530/EC-20-0152. 32688339 PMC7424338 · DOI
  44. [65]Huby T, and Gautier EL (2022). Immune cell-mediated features of non-alcoholic steatohepatitis. Nat Rev Immunol 22, 429– 443. 10.1038/s41577-021-00639-3. 34741169 PMC8570243 · DOI · Paper page
  45. [66]Reibe S, and Febbraio MA (2019). Author Correction: Relieving ER stress to target NASH-driven hepatocellular carcinoma. Nat Rev Endocrinol 15, 126. 10.1038/s41574-019-0154-1. 30610220 · DOI
  46. [67]Zsombok A, Desmoulins LD, and Derbenev AV (2024). Sympathetic circuits regulating hepatic glucose metabolism: where we stand. Physiol Rev 104, 85– 101. 10.1152/physrev.00005.2023. 37440208 PMC11281813 · DOI
  47. [68]Adori M, Bhat S, Gramignoli R, Valladolid-Acebes I, Bengtsson T, Uhlen M, and Adori C (2023). Hepatic Innervations and Nonalcoholic Fatty Liver Disease. Semin Liver Dis 43, 149– 162. 10.1055/s-0043-57237. 37156523 PMC10348844 · DOI
  48. [69]Sjoberg KA, Sigvardsen CM, Alvarado-Diaz A, Andersen NR, Larance M, Seeley RJ, Schjerling P, Knudsen JG, Katzilieris-Petras G, Clemmensen C, (2023). GDF15 increases insulin action in the liver and adipose tissue via a beta-adrenergic receptor-mediated mechanism. Cell Metab 35, 1327– 1340 e1325. 10.1016/j.cmet.2023.06.016. 37473755 · DOI
  49. [72]Lan T, Morgan DA, Rahmouni K, Sonoda J, Fu X, Burgess SC, Holland WL, Kliewer SA, and Mangelsdorf DJ (2017). FGF19, FGF21, and an FGFR1/beta-Klotho-Activating Antibody Act on the Nervous System to Regulate Body Weight and Glycemia. Cell Metab 26, 709– 718 e703. 10.1016/j.cmet.2017.09.005. 28988823 PMC5679468 · DOI · Paper page
  50. [73]Klett EL, Lu K, Kosters A, Vink E, Lee MH, Altenburg M, Shefer S, Batta AK, Yu H, Chen J, (2004). A mouse model of sitosterolemia: absence of Abcg8/sterolin-2 results in failure to secrete biliary cholesterol. BMC Med 2, 5. 10.1186/1741-7015-2-5. 15040800 PMC394351 · DOI
  51. [74]Yu L, Li-Hawkins J, Hammer RE, Berge KE, Horton JD, Cohen JC, and Hobbs HH (2002). Overexpression of ABCG5 and ABCG8 promotes biliary cholesterol secretion and reduces fractional absorption of dietary cholesterol. J Clin Invest 110, 671– 680. 10.1172/JCI16001. 12208868 PMC151111 · DOI
  52. [75]Kosters A, Frijters RJ, Schaap FG, Vink E, Plosch T, Ottenhoff R, Jirsa M, De Cuyper IM, Kuipers F, and Groen AK (2003). Relation between hepatic expression of ATP-binding cassette transporters G5 and G8 and biliary cholesterol secretion in mice. J Hepatol 38, 710– 716. 10.1016/s0168-8278(03)00093-x. 12763362 · DOI
  53. [77]Chen MM, Hale C, Stanislaus S, Xu J, and Veniant MM (2018). FGF21 acts as a negative regulator of bile acid synthesis. J Endocrinol 237, 139– 152. 10.1530/JOE-17-0727. 29615519 · DOI
  54. [78]Gaich G, Chien JY, Fu H, Glass LC, Deeg MA, Holland WL, Kharitonenkov A, Bumol T, Schilske HK, and Moller DE (2013). The effects of LY2405319, an FGF21 analog, in obese human subjects with type 2 diabetes. Cell Metab 18, 333– 340. 10.1016/j.cmet.2013.08.005. 24011069 · DOI · Paper page
  55. [79]Talukdar S, Zhou Y, Li D, Rossulek M, Dong J, Somayaji V, Weng Y, Clark R, Lanba A, Owen BM, (2016). A Long-Acting FGF21 Molecule, PF-05231023, Decreases Body Weight and Improves Lipid Profile in Non-human Primates and Type 2 Diabetic Subjects. Cell Metab 23, 427– 440. 10.1016/j.cmet.2016.02.001. 26959184 · DOI · Paper page
  56. [82]Patro R, Duggal G, Love MI, Irizarry RA, and Kingsford C (2017). Salmon provides fast and bias-aware quantification of transcript expression. Nat Methods 14, 417– 419. 10.1038/nmeth.4197. 28263959 PMC5600148 · DOI · Paper page
  57. [83]Love MI, Huber W, and Anders S (2014). Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol 15, 550. 10.1186/s13059-014-0550-8. 25516281 PMC4302049 · DOI · Paper page
  58. [84]Yu G, Wang LG, Han Y, and He QY (2012). clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS 16, 284– 287. 10.1089/omi.2011.0118. 22455463 PMC3339379 · DOI · Paper page
  59. [85]Gu Z (2022). Complex heatmap visualization. Imeta 1, e43. 10.1002/imt2.43. 38868715 PMC10989952 · DOI
  60. [86]Stuart T, Butler A, Hoffman P, Hafemeister C, Papalexi E, Mauck WM 3rd, Hao Y, Stoeckius M, Smibert P, and Satija R (2019). Comprehensive Integration of Single-Cell Data. Cell 177, 1888– 1902 e1821. 10.1016/j.cell.2019.05.031. 31178118 PMC6687398 · DOI · Paper page
  61. [88]Thiele SL, Warre R, and Nash JE (2012). Development of a unilaterally-lesioned 6-OHDA mouse model of Parkinson’s disease. J Vis Exp. 10.3791/3234. PMC3376941 22370630 · DOI
  62. [89]Hasan MN, Wang H, Luo W, Clayton YD, Gu L, Du Y, Palle SK, Chen J, and Li T (2024). Gly-beta-MCA is a potent anti-cholestasis agent against “human-like” hydrophobic bile acid-induced biliary injury in mice. J Lipid Res 65, 100649. 10.1016/j.jlr.2024.100649. 39306039 PMC11526081 · DOI
  63. [90]Fu X, Deja S, Fletcher JA, Anderson NN, Mizerska M, Vale G, Browning JD, Horton JD, McDonald JG, Mitsche MA, and Burgess SC (2021). Measurement of lipogenic flux by deuterium resolved mass spectrometry. Nat Commun 12, 3756. 10.1038/s41467-021-23958-4. 34145255 PMC8213799 · DOI
  64. [91]Millar JS, Cromley DA, McCoy MG, Rader DJ, and Billheimer JT (2005). Determining hepatic triglyceride production in mice: comparison of poloxamer 407 with Triton WR-1339. J Lipid Res 46, 2023– 2028. 10.1194/jlr.D500019-JLR200. 15995182 · DOI
  65. [92]Bell BB, Harlan SM, Morgan DA, Guo DF, Cui H, and Rahmouni K (2018). Differential contribution of POMC and AgRP neurons to the regulation of regional autonomic nerve activity by leptin. Mol Metab 8, 1– 12. 10.1016/j.molmet.2017.12.006. 29289646 PMC5985226 · DOI
  66. [93]Tanida M, Yamamoto N, Morgan DA, Kurata Y, Shibamoto T, and Rahmouni K (2015). Leptin receptor signaling in the hypothalamus regulates hepatic autonomic nerve activity via phosphatidylinositol 3-kinase and AMP-activated protein kinase. J Neurosci 35, 474– 484. 10.1523/JNEUROSCI.1828-14.2015. 25589743 PMC4293404 · DOI
  67. [94]Brandt C, Nolte H, Henschke S, Engstrom Ruud L, Awazawa M, Morgan DA, Gabel P, Sprenger HG, Hess ME, Gunther S, (2018). Food Perception Primes Hepatic ER Homeostasis via Melanocortin-Dependent Control of mTOR Activation. Cell 175, 1321– 1335 e1320. 10.1016/j.cell.2018.10.015. 30445039 PMC6541012 · DOI

Cited by

Sorted by citations

Authors
Rose, J. P., Morgan, D. A., Sullivan, A. I., Fu, X., Inigo-Vollmer, M., Burgess, S. C., Meyerholz, D. K., Rahmouni, K., & Potthoff, M. J.
Affiliations
  • University of Iowa (US)
  • The University of Texas Southwestern Medical Center (US)
Corresponding author
Potthoff, Matthew J.
ORCID
Venue
Cell Metabolism
Publisher
Elsevier BV
Published
2025-07
Volume
37
Issue
7
Pages
1515-1529.e6
ISSN
1550-4131 (ISSN-L)
DOI
10.1016/j.cmet.2025.04.014
PMC
PMC12409791
OpenAlex
W4410316023
Cited by
75
References
27
Citations by year
2026: 54 · 2025: 21
FWCI
22.55
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Metabolism (acceptedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion)
Funders
  • US Department of Veterans Affairs (I01BX004634, IK6BX006040)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01HL162773, R01AA027654, R01DK106104, P30DK54759)
  • Cystic Fibrosis Foundation
  • National Institutes of Health
  • Roy J. and Lucille A. Carver College of Medicine, University of Iowa
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Keywords
FGF21, nonalcoholic steatohepatitis, non-alcoholic fatty liver disease, hepatic steatosis, liver fibrosis, hepatic triglycerides, liver cholesterol, glutamatergic neurons, central nervous system signaling, sympathetic activity, de novo lipogenesis, hepatocytes, diet-induced liver disease
MeSH terms
Animals, Central Nervous System, Cholesterol, Fatty Liver, Fibroblast Growth Factors, Humans, Liver, Male, Mice, Inbred C57BL, Triglycerides, Signal Transduction, 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