Frank J Gonzalez


Affiliation: National Institutes of Health
Country: USA


  1. request reprint
    Gonzalez F. Regulation of hepatocyte nuclear factor 4 alpha-mediated transcription. Drug Metab Pharmacokinet. 2008;23:2-7 pubmed
    ..The ability of HNF4alpha to be regulated offers hope that it could be a drug target. ..
  2. Brocker C, Patel D, Velenosi T, Kim D, Yan T, Yue J, et al. Extrahepatic PPARα modulates fatty acid oxidation and attenuates fasting-induced hepatosteatosis in mice. J Lipid Res. 2018;59:2140-2152 pubmed publisher
    ..This has important clinical implications in disease states with impaired hepatic PPARA function, such as nonalcoholic steatohepatitis and nonalcoholic fatty liver disease. ..
  3. Yan T, Wang H, Cao L, Wang Q, Takahashi S, Yagai T, et al. Glycyrrhizin Alleviates Nonalcoholic Steatohepatitis via Modulating Bile Acids and Meta-Inflammation. Drug Metab Dispos. 2018;46:1310-1319 pubmed publisher
    ..These results reveal that GL, via restoration of bile acid homeostasis and inhibition of inflammatory injury, can be a therapeutic option for treatment of NASH. ..
  4. Xie C, Jiang C, Shi J, Gao X, Sun D, Sun L, et al. An Intestinal Farnesoid X Receptor-Ceramide Signaling Axis Modulates Hepatic Gluconeogenesis in Mice. Diabetes. 2017;66:613-626 pubmed publisher
    ..These results reveal a mechanism by which the dietary supplement CAPE and intestinal FXR regulates hepatic gluconeogenesis and suggest that inhibiting intestinal FXR is a strategy for treating hyperglycemia. ..
  5. Hayashi Y, Ito Y, Naito H, Tamada H, Yamagishi N, Kondo T, et al. In utero exposure to di(2-ethylhexyl)phthalate suppresses blood glucose and leptin levels in the offspring of wild-type mice. Toxicology. 2019;415:49-55 pubmed publisher
    ..DEHP also decreases serum and plasma leptin concentrations in offspring during the neonatal and weaning periods, in association with PPARα, which presumably results in increased of food consumption after weaning. ..
  6. Gonzalez F, Jiang C. A Western diet-induced mouse model reveals a possible mechanism by which metformin decreases obesity. Eur J Clin Pharmacol. 2017;73:1337-1339 pubmed publisher
  7. Gonzalez F, Xie C, Jiang C. The role of hypoxia-inducible factors in metabolic diseases. Nat Rev Endocrinol. 2018;15:21-32 pubmed publisher
    ..Inhibition of HIF1α and HIF2α decreases the adverse diet-induced metabolic phenotypes, suggesting that they could be drug targets for the treatment of metabolic diseases. ..
  8. Zhang Y, Yan T, Sun D, Xie C, Zheng Y, Zhang L, et al. Structure-Activity Relationships of the Main Bioactive Constituents of Euodia rutaecarpa on Aryl Hydrocarbon Receptor Activation and Associated Bile Acid Homeostasis. Drug Metab Dispos. 2018;46:1030-1040 pubmed publisher
    ..rutaecarpa. ..
  9. Manna S, Golla S, Golla J, Tanaka N, Cai Y, Takahashi S, et al. St. John's Wort Attenuates Colorectal Carcinogenesis in Mice through Suppression of Inflammatory Signaling. Cancer Prev Res (Phila). 2015;8:786-95 pubmed publisher
    ..In conclusion, this study demonstrated the chemopreventive potential of SJW extract against colorectal cancer through attenuation of proinflammatory processes. ..

More Information


  1. Manna S, Tanaka N, Krausz K, Haznadar M, Xue X, Matsubara T, et al. Biomarkers of coordinate metabolic reprogramming in colorectal tumors in mice and humans. Gastroenterology. 2014;146:1313-24 pubmed publisher
    ..These urine and tissue markers might be used in early detection of colorectal cancer. ..
  2. Fang Z, Tosh D, Tanaka N, Wang H, Krausz K, O CONNOR R, et al. Metabolic mapping of A3 adenosine receptor agonist MRS5980. Biochem Pharmacol. 2015;97:215-23 pubmed publisher
    ..These data will be useful to guide rational design of drugs targeting A3AR, considering efficacy, metabolic elimination, and electrophilic reactivity. ..
  3. Gonzalez F, Fang Z, Ma X. Transgenic mice and metabolomics for study of hepatic xenobiotic metabolism and toxicity. Expert Opin Drug Metab Toxicol. 2015;11:869-81 pubmed publisher
  4. Cao G, Xu W, Yang X, Gonzalez F, Li F. New neolignans from the seeds of Myristica fragrans that inhibit nitric oxide production. Food Chem. 2015;173:231-7 pubmed publisher
    ..These results demonstrated that the 8-O-4' type neolignans are promising candidates as anti-inflammatory agents. ..
  5. Tanaka N, Takahashi S, Fang Z, Matsubara T, Krausz K, Qu A, et al. Role of white adipose lipolysis in the development of NASH induced by methionine- and choline-deficient diet. Biochim Biophys Acta. 2014;1841:1596-607 pubmed publisher
    ..Collectively, these results demonstrate an important role for dietary methionine deficiency and WAT lipolysis in the development of MCD-NASH. ..
  6. Wang H, Fang Z, Zheng Y, Zhou K, Hu C, Krausz K, et al. Metabolic profiling of praziquantel enantiomers. Biochem Pharmacol. 2014;90:166-78 pubmed publisher
    ..In conclusion, in silico, in vitro, and in vivo methods revealed the enantioselective metabolic profile of praziquantel. ..
  7. Qu A, Jiang C, Cai Y, Kim J, Tanaka N, Ward J, et al. Role of Myc in hepatocellular proliferation and hepatocarcinogenesis. J Hepatol. 2014;60:331-8 pubmed publisher
    ..Myc plays an essential role in hepatocellular proliferation and liver tumorigenesis. ..
  8. Cheng J, Fang Z, Nagaoka K, Okamoto M, Qu A, Tanaka N, et al. Activation of intestinal human pregnane X receptor protects against azoxymethane/dextran sulfate sodium-induced colon cancer. J Pharmacol Exp Ther. 2014;351:559-67 pubmed publisher
    ..These results suggested that specific activation of intestinal human PXR exhibited a chemopreventive role toward AOM/DSS-induced colon cancer by mediating anti-inflammation, antiproliferation, and proapoptotic events. ..
  9. Tanaka N, Takahashi S, Matsubara T, Jiang C, Sakamoto W, Chanturiya T, et al. Adipocyte-specific disruption of fat-specific protein 27 causes hepatosteatosis and insulin resistance in high-fat diet-fed mice. J Biol Chem. 2015;290:3092-105 pubmed publisher
  10. Gao X, Xie C, Wang Y, Luo Y, Yagai T, Sun D, et al. The antiandrogen flutamide is a novel aryl hydrocarbon receptor ligand that disrupts bile acid homeostasis in mice through induction of Abcc4. Biochem Pharmacol. 2016;119:93-104 pubmed publisher
    ..These findings provide new insights into the mechanism of liver injury caused by FLU treatment involving activation of AhR and the alterations of bile acid homeostasis, which could guide clinical application. ..
  11. Xie C, Gao X, Sun D, Zhang Y, Krausz K, Qin X, et al. Metabolic Profiling of the Novel Hypoxia-Inducible Factor 2α Inhibitor PT2385 In Vivo and In Vitro. Drug Metab Dispos. 2018;46:336-345 pubmed publisher
    ..This study provides metabolic data and an important reference basis for the safety evaluation and rational clinical application of PT2385. ..
  12. Brocker C, Yue J, Kim D, Qu A, Bonzo J, Gonzalez F. Hepatocyte-specific PPARA expression exclusively promotes agonist-induced cell proliferation without influence from nonparenchymal cells. Am J Physiol Gastrointest Liver Physiol. 2017;312:G283-G299 pubmed publisher
    ..These studies conclusively show that cell proliferation is mediated exclusively by PPARA activation in hepatocytes and that Kupffer cell PPARA has an important role in mediating the anti-inflammatory effects of PPARA agonists. ..
  13. Gonzalez F, Jiang C, Patterson A. An Intestinal Microbiota-Farnesoid X Receptor Axis Modulates Metabolic Disease. Gastroenterology. 2016;151:845-859 pubmed publisher
    ..These studies show that ceramides produced in the ileum under control of FXR influence metabolic diseases. ..
  14. Fang Z, Zhang D, Cao Y, Xie C, Lu D, Sun D, et al. Irinotecan (CPT-11)-induced elevation of bile acids potentiates suppression of IL-10 expression. Toxicol Appl Pharmacol. 2016;291:21-7 pubmed publisher
    ..These results showed that CPT-11 treatment caused metabolic changes in the composition of bile acids that altered CPT-11-induced suppression of IL-10 expression. ..
  15. Li G, Xie C, Lu S, Nichols R, Tian Y, Li L, et al. Intermittent Fasting Promotes White Adipose Browning and Decreases Obesity by Shaping the Gut Microbiota. Cell Metab. 2017;26:672-685.e4 pubmed publisher
    ..These findings provide a new gut-microbiota-driven mechanism for activating adipose tissue browning and treating metabolic diseases. ..
  16. Li G, Brocker C, Yan T, Xie C, Krausz K, Xiang R, et al. Metabolic adaptation to intermittent fasting is independent of peroxisome proliferator-activated receptor alpha. Mol Metab. 2018;7:80-89 pubmed publisher
    ..Therefore, PPARA activation does not mediate the metabolic adaptation to fasting, at least in preventing acute fasting-induced steatosis. ..
  17. Li F, Zhu W, Gonzalez F. Potential role of CYP1B1 in the development and treatment of metabolic diseases. Pharmacol Ther. 2017;178:18-30 pubmed publisher
    ..Therefore, it may be feasible to consider CYP1B1 as a therapeutic target for the treatment of metabolic diseases. ..
  18. Hao H, Cao L, Jiang C, Che Y, Zhang S, Takahashi S, et al. Farnesoid X Receptor Regulation of the NLRP3 Inflammasome Underlies Cholestasis-Associated Sepsis. Cell Metab. 2017;25:856-867.e5 pubmed publisher
    ..These findings suggest that bile acids and FXR play pivotal roles in sepsis via controlling the NLRP3 inflammasome, and that targeting FXR may represent a therapeutic strategy for cholestasis-associated sepsis. ..
  19. Wang H, Fang Z, Meng R, Cao Y, Tanaka N, Krausz K, et al. Glycyrrhizin and glycyrrhetinic acid inhibits alpha-naphthyl isothiocyanate-induced liver injury and bile acid cycle disruption. Toxicology. 2017;386:133-142 pubmed publisher
    ..These results suggested that GL/GA could prevent drug-induced liver injury and ensuing disruption of bile acid metabolism in humans. ..
  20. Fang Z, Tanaka N, Lu D, Jiang C, Zhang W, Zhang C, et al. Role of the lipid-regulated NF-κB/IL-6/STAT3 axis in alpha-naphthyl isothiocyanate-induced liver injury. Arch Toxicol. 2017;91:2235-2244 pubmed publisher
  21. Hong X, Zheng Y, Qin Z, Wu B, Dai Y, Gao H, et al. In Vitro Glucuronidation of Wushanicaritin by Liver Microsomes, Intestine Microsomes and Expressed Human UDP-Glucuronosyltransferase Enzymes. Int J Mol Sci. 2017;18: pubmed publisher
    ..Taken together, UGT1A1, 1A3, 1A7, 1A8, 1A9 and 2B7 were identified as the main UGT contributors responsible for wushanicaritin glucuronidation. ..
  22. Takahashi S, Fukami T, Masuo Y, Brocker C, Xie C, Krausz K, et al. Cyp2c70 is responsible for the species difference in bile acid metabolism between mice and humans. J Lipid Res. 2016;57:2130-2137 pubmed
    ..Because humans do not produce MCA, they lack tauro-?-MCA, a farnesoid X receptor antagonist in mouse that modulates obesity, insulin resistance, and hepatosteatosis. ..
  23. Tanaka N, Takahashi S, Zhang Y, Krausz K, Smith P, Patterson A, et al. Role of fibroblast growth factor 21 in the early stage of NASH induced by methionine- and choline-deficient diet. Biochim Biophys Acta. 2015;1852:1242-52 pubmed publisher
    ..Collectively, FGF21 is elevated in the early stage of MCD-induced NASH likely to minimize hepatic lipid accumulation and ensuing ER stress. These results provide a possible mechanism on how FGF21 is increased in NAFLD/NASH. ..
  24. Gonzalez F. Nuclear receptor control of enterohepatic circulation. Compr Physiol. 2012;2:2811-28 pubmed publisher
    ..Each bile acid is reabsorbed about 20 times on average before being eliminated. Enterohepatic circulation is under tight regulation by nuclear receptor signaling, notably by the farnesoid X receptor (FXR). ..
  25. Fang Z, Krausz K, Tanaka N, Li F, Qu A, Idle J, et al. Metabolomics reveals trichloroacetate as a major contributor to trichloroethylene-induced metabolic alterations in mouse urine and serum. Arch Toxicol. 2013;87:1975-1987 pubmed publisher
    ..These data show the metabolic response to TCE exposure and demonstrate that TCA is the major contributor to TCE-induced metabolite alterations observed in urine and serum. ..
  26. Tanaka N, Takahashi S, Hu X, Lu Y, Fujimori N, Golla S, et al. Growth arrest and DNA damage-inducible 45α protects against nonalcoholic steatohepatitis induced by methionine- and choline-deficient diet. Biochim Biophys Acta Mol Basis Dis. 2017;1863:3170-3182 pubmed publisher
    ..e., "burned-out" NASH). ..