Matthew J. Potthoff, PhD

Portrait
Director of Molecular Medicine PhD Program
Associate Professor of Pharmacology

Contact Information

Primary Office: 3322 Pappajohn Biomedical Discover Building
Iowa City, IA 52242
319-384-4438

Lab: 3310C Pappajohn Biomedical Discovery Building
Iowa City, IA 52242
319-335-7660

Education

BS, Suma Cum Laude, Biology / Zoology, University of Oklahoma
PhD, Genetics and Development, University of Texas Southwestern Medical Center

Fellow, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center

Education/Training Program Affiliations

Interdisciplinary Graduate Program in Genetics, Interdisciplinary Graduate Program in Molecular and Cellular Biology

Center, Program and Institute Affiliations

Center for Gene Therapy of Cystic Fibrosis and other Genetic Diseases, Fraternal Order of Eagles Diabetes Research Center

Research Summary

Nutrient Control of Hepatic Metabolism and Signaling

The regulation of metabolic homeostasis is a complex process coordinated by numerous growth factors and hormones signaling the availability of energy and nutrients. While it is well known that the liver functions to maintain energy homeostasis by producing energy sources for other cells during nutrient deprivation, the liver is also becoming recognized as a major regulator of systemic energy metabolism through production of hepatokines. These liver derived hormones signal nutrient availability to other tissues and control substrate utilization to maintain energy balance. My lab is interested in unraveling these hepatic pathways that govern systemic energy balance by focusing on known and novel hepatokines. The purpose is two-fold: 1) secreted factors are a rich source of new therapeutics because they are designed to circulate and signal, and 2) nutrient signaling is dysregulated in several diseases including diabetes and cancer. To identify and examine hepatokine function, my lab integrates biochemistry, proteomics, cell biology, metabolomics, and mouse genetics. By unraveling these liver-derived networks, we hope to identify a new therapeutic to treat obesity and metabolic disease.

Publications

Markan, K. R., Naber, M. C., Small, S. M., Peltekian, L., Kessler, R. L. & Potthoff, M. J. (2017). FGF21 resistance is not mediated by downregulation of beta-klotho expression in white adipose tissue. Mol Metab, 6(6), 602-610. PMID: 28580290.

Potthoff, M. J. (2017). FGF21 and metabolic disease in 2016: A new frontier in FGF21 biology. (Vols. 13). (2), pp. 74-76. Nat Rev Endocrinology. PMID: 27983736.

Soberg, S., Sandholt, C. H., Jespersen, N. Z., Toft, U., Madsen, A. L., von Holstein-Rathlou, S., Grevengoed, T. J., Christensen, K. B., Bredie, W., Potthoff, M. J., Solomon, T., Scheele, C., Linneberg, A., Jorgensen, T., Pedersen, O., Hansen, T., Gillum, M. P. & Grarup, N. (2017). FGF21 Is a Sugar-Induced Hormone Associated with Sweet Intake and Preference in Humans. Cell Metab, 25(5), 1045-1053. PMID: 28467924.

BonDurant, L. D., Ameka, M., Naber, M. C., Markan, K. R., Idiga, S. O., Acevedo, M. R., Walsh, S. A., orntiz, D. M. & Potthoff, M. J. (2017). FGF21 Regulates Metabolism Through Adipose-Dependent and -Independent Mechanisms. Cell Metab, 25(4), 935-944. PMID: 28380381.

Cushing, E. M., Chi, X., Sylvers, K. L., Shetty, S. K., Potthoff, M. J. & Davies BSJ, (2017). Angiopoietin-like 4 directs uptake of dietary fat away from adipose during fasting. Molecular metabolism, 6(8), 809-818. PMID: 28752045.

Pereira, R. O., Tadinada, S. M., Zasadny, F. M., Oliveira, K. J., Pires, K., Olvera, A., Jeffers, J., Souvenir, R., Mcglauflin, R., Seei, A., Funari, T., Sesaki, H., Potthoff, M. J., Adams, C. M., Anderson, E. J. & Abel, E. D. (2017). OPA1 deficiency promotes secretion of FGF21 from muscle that prevents obesity and insulin resistance. EMBO J, 36(14), 2126-2145. PMID: 28607005.

von Holstein-Rathlou, S., BonDurant, L., Peltekian, L., Naber, M. C., Yin, T. C., Claflin, K. E., Ibarra Urizar, A., Madsen, A. N., Ratner, C., Holst, B., Karstoft, K., Vandenbeuch, A., Anderson, C. B., Cassell, M. D., Thompson, A. P., Solomon, T. P., Rahmouni, K., Kinnamon, S. C., Pieper, A. A., Gillum, M. P. & Potthoff, M. J. (2016). FGF21 Mediates Endocrine Control of Simple Sugar Intake and Sweet Taste Preference by the Liver. Cell Metabolism, 23(2), 335-43. PMID: 2672858.

Markan, K. R., Potthoff, M. J. (2016). Metabolic fibroblast growth factors (FGFs): Mediators of energy homeostasis. Semin Cell Dev Biol, 53(85-93). PMID: 26428296.

Kolb, R., Phan, L., Borcherding, N., Liu, Y., Yuan, F., Janowski, A. M., Xie, Q., Markan, K. R., Li, W., Potthoff, M. J., Fuentes-Mattei, E., Ellies, L. G., Knudson, C. M., Lee, M. H., Yeung, S. J., Cassel, S. L., Sutterwala, F. S. & Zhang, W. (2016). Obesity-associated NLRC4 inflammasome activation drives breast cancer progression. Nat Commun, 7, 13007. PMID: 27708283.

Gillum, M. P., Potthoff, M. J. (2016). FAP finds FGF21 easy to digest. Biochem J, 473(9), 1125-7. PMID: 27118870.

Littlejohn, N. K., keen, H. L., Weidemann, B. J., Claflin, K. E., Tobin, K. V., Markin, K. R., Park, S., Naber, M. C., Gourronc, F. A., Pearson, N. A., Liu, X., Morgan, D. A., Klingelhutz, A. J., Potthoff, M. J., Rahmouni, K., Sigmund, C. D. & Grobe, J. L. (2016). Suppression of Resting Metabolism by the Angiotensin AT2 Receptor. Cell Rep, 16(6), 1548-60. PMID: 27477281.

Gray, L. R., Sultana, M. R., Rauckhorst, A. J., Oonthonpan, L., Tompkins, S. C., Sharma, A., Fu, X., Miao, R., Pewa, A. D., Brown, K. S., Lane, E. E., Dohlman, A., Zepeda-Orozco, D., Xie, J., Rutter, J., Norris, A. W., Cox, J. E., Burgess, S. C., Potthoff, M. J. & Taylor, E. B. (2015). Hepatic Mitochondrial Pyruvate Carrier 1 is Required for Efficient Regulation of Gluconeogenesis and Whole-body Glucose Homeostasis. Cell Metabolism, 22(4), 669-81.

Markan, K. R., Potthoff, M. J. (2015). Metabolic fibroblast growth factors (FGFs): Mediators of energy homeostasis. Semin Cell Dev Biol, S1084-9521(15)00181-0. DOI: 10.1016/j.semcdb.2015.09.021.

Gray, L. R., Sultana, M. R., Rauckhorst, A. J., Oonthonpan, L., Tompkins, S. C., Sharma, A., Fu, X., Miao, R., Pewa, A. D., Brown, K. S., Lane, E. E., Dohlman, A., Zepeda-Orozco, D., Xie, J., Norris, A. W., Cox, J. E., Burgess, S. C., Potthoff, M. J. & Taylor, E. B. (2015). Hepatic Mitochondrial Pyruvate Carrier 1 is Required for Efficient Regulation of Gluconeogenesis and Whole-body Glucose Homeostasis. Cell Metabolism, 22(4), 669-681.

McGlashon, J. M., Gorecki, M. C., Kozlowski, A. E., Thimbeck, C. K., Markan, K. R., Leslie, K. L., Kotas, M. E., Potthoff, M. J., Richerson, G. B. & Gillum, M. P. (2015). Central serotonergic neurons activate and recruit thermogenic brown and beige fat and regulate glucose and lipid homeostasis. Cell Metabolism, 21(5), 692-705.

Potthoff, M. J., Kliewer, S. A. & Mangelsdorf, D. J. (2014). Endocrine fibroblast growth factors 15/19 and 21: From feast to famine. Genes Dev, 26(4), 312-324. PMID: 22302876.

Markan, K. R., Naber, M. c., Ameka, M. K., Anderegg, M. D., Mangelsdorf, D. J., Kliewer, S. A., Mohammadi, M. & Potthoff, M. J. (2014). Circulating FGF21 is Liver Derived and Enhances Glucose Uptake During Refeeding and Overfeeding. Diabetes, 63(12), 4057-4063.

Potthoff, M. J., Finck, B. N. (2014). Head Over Hepatocytes for FGF21. (Vols. 63). (12), pp. 4013. Diabetes. PMID: 25414019.

Potthoff, M. J., Potts, A., He, T., Duarte, J. A., Taussig, R., Mangelsdorf, D. J., Kliewer, S. A. & Burgess, S. C. (2013). Colesevelam Suppresses Hepatic Glycogenolysis by TGR5-mediated Induction of GLP-1 Action in DIO Mice. Am J Physiol: Gastrointestinal and Liver Physiol, 304(4), G371-G380. PMID: 23257920.

Potthoff, M. J., Kliewer, S. A. & Mangelsdorf, D. J. (2012). Endocrine Fibroblast Growth Factors 15/19 and 21: From Feast to Famine. Genes Dev, 26(4), 312-324.

Zhang, Y., Xie, Y., Berglund, E. D., Coate, K. C., He, T. T., Katafuchi, T., Xiao, G., Potthoff, M. J., Wei, W., Wan, Y., Yu, R. T., Evans, R. M., Kliewer, S. A. & Mangelsdorf, D. J. (2012). The Starvation Hormone, Fibroblast Growth Factor-21, Extends Lifespan in Mice. elife, 1, e00065. DOI: 10.7554/3Life.00065.

Potthoff, M. J., Boney-Montoya, J., Choi, M., Satapati, S., He, T., Suino-Powell, K., Xu, H. E., Gerard, R. D., Finck, B. N., Burgess, S. C., Mangelsdorf, D. J. & Kliewer, S. A. (2011). FGF15/19 Regulates Hepatic Glucose Metabolism By Inhibiting the CREB-PGC-1a Pathway. Cell Metabolism, 13(6), 729-738.

Moresi, V., Williams, A. H., Meadows, E., Flynn, J. M., Potthoff, M. J., McAnally, J., Shelton, J. M., Backs, J., Klein, W. H., Richardson, J. A., Bassel-Duby, R. & Olson, E. N. (2010). Myogenin and Class II HDACs Control Neurogenic Muscle Atrophy by Inducing E3 Ubiquitin Ligases. Cell, 143(1), 35-45. PMID: 20887891.

Sunny, N. E., Satapati, S., Fu, X., He, T., Mehdibeigi, R., Spring-Robinson, C., Duarte, J., Potthoff, M. J., Browning, J. D. & Burgess, S. C. (2010). Progressive adaptation of hepatic ketogenesis in mice fed a high-fat diet. Am J Physiol Endocrinol Metab, 298(6), E1226-E1235. PMID: 20233938.

Potthoff, M. J., Inagaki, T., Boney-Montoya, J., Ding, X., He, T., Finck, B. N., Mangelsdorf, D. J., Burgess, S. C. & Kliewer, S. A. (2010). “FGF15/19 and FGF21 Govern Fed and Fasted Responses in Liver Through Reciprocal Regulation of PGC-1a.”. In Oral Presentation and Poster Presentation. Deuel Lipid Conference 2010. Dana Point, CA.

Potthoff, M. J., Inagaki, T., Satapati, S., Ding, X., He, T., Goetz, R., Mohammadi, M., Finck, B. N., Mangelsdorf, D. J., Kliewer, S. A. & Burgess, S. C. (2009). FGF21 Induces PGC-1alpha and Regulates Carbohydrate and Fatty Acid Metabolism During the Adaptive Starvation Response. Proc Natl Acad Sci U S A, 106(26), 10853-10858. PMID: 19541642.

Satapati, S., He, T., Inagaki, T., Potthoff, M. J., Merritt, M. E., Esser, V., Mangelsdorf, D. J., Kliewer, S. A., Browning, J. D. & Burgess, S. C. (2008). Partial resistance to peroxisome proliferator-activated receptor-alpha agonists in ZDF rats is associated with defective hepatic mitochondrial metabolism. Diabetes, 57(8), 2012-2021. PMID: 18469201.

Potthoff, M. J., Wu, H., Arnold, M. A., Shelton, J. M., Backs, J., McAnally, J., Bassel-Duby, R. & Olson, E. N. (2007). "Regulation of Skeletal Myofiber Identity by Selective Degradation of Class II HDACs.". In Abstract and Poster Presentation. Symposium on Biological Complexity: Diseases of Transcription, Salk Institute, La Jolla, CA.

Potthoff, M. J., Olson, E. N. (2007). A central regulator of diverse developmental programs. Development, 134(23), 4131. PMID: 17959722.

Potthoff, M. J., Wu, H., Arnold, M. A., Shelton, J. M., Backs, J., McAnally, J., Richardson, J. A., Bassel-Duby, R. & Olson, E. N. (2007). Histone deacetylase degradation and MEF2 activation promote the formation of slow-twitch myofibers. J Clin Invest, 117(9), 2459-2467. PMID: 17786239.

Potthoff, M. J., Olson, E. N. & Bassel-Duby, R. (2007). Skeletal muscle remodeling. Curr Opin Rheumatol, 19(6), 542. PMID: 17917533.

Potthoff, M. J., Wu, H., Arnold, M. A., Shelton, J. M., Backs, J., Richardson, J. A., Bassel-Duby, R. & Olson, E. N. (2007). Histone Deacetylase Degradation and MEF2 Activation Promote the Formation of Slow-twitch Myofibers. J Clin Invest, 117(9), 2459-2467.

Montgomery, R. L., Davis, C. A., Potthoff, M. J., Haberland, M., Fielitz, J., Qi, X., Hill, J. A., Richardson, J. A. & Olson, E. N. (2007). Histone deacetylases 1 and 2 redundantly regulate cardiac morphogenesis, growth, and contractility. Genes Dev, 21(14), 1790-1802. PMID: 17639084.