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Matthew Potthoff, PhD

Director, Molecular Medicine Program, Associate Professor
Neuroscience and Pharmacology

Office: 3322 PBDB
Office Phone: 319-384-4438

Lab: 3322 PBDB

Lab Website: https://potthoff.lab.uiowa.edu/

Nutrient Control of Metabolism and Cell Signaling

The regulation of metabolic homeostasis is a complex process coordinated by numerous growth factors and hormones signaling the availability of energy and nutrients. Organisms must properly perceive and respond to these signals to maintain homeostasis. The main goals of my lab are: 1) to identify secreted proteins and transcription factors that regulate nutritional status and contribute to metabolic disease, 2) to determine molecular mechanisms for these signals, 3) to understand how these pathways regulate biological functions, and 4) how dysregulation of these pathways contribute to metabolic disease (i.e., in diabetes and cancer). We currently have multiple projects aimed at addressing these goals, with the two main projects focused on the endocrine fibroblast growth hormone 21 (FGF21) and a hepatic transcription factor termed Tox. Pharmacological studies have shown that FGF21 administration markedly improves insulin sensitivity, lowers lipid levels, and reduces body weight in obese animal models. Thus, FGF21 remarkably improves a number of metabolic parameters in obese rodents. The mechanism by which endocrine FGFs perform these remarkable pharmacologic effects on carbohydrate and lipid metabolism is largely unknown and is currently an area of interest of the lab.

A second line of investigation in the lab is how Tox, a transcription factor, regulates hepatic lipid and glucose metabolism in vivo. Using genetically engineered gain- and loss-of-function mouse models, we will elucidate the function of Tox in regulating hepatic lipid and glucose metabolism during fasting and obesity. The precise mechanism of Tox action is unclear, but we are currently using multiple techniques to identify Tox target genes in the liver and the mechanism by which it regulates carbohydrate and lipid metabolism in vivo. By identifying and studying pathways which signal energy and nutrient availability, we hope to gain insight into metabolic dysfunction and find novel candidates for the treatment of metabolic disease.

PubMed link

Department/Program Affiliations:
Molecular Medicine
Neuroscience and Pharmacology