Regulation of Metabolism and Appetite in the Shulman-Petersen-Gillum Group

The Shulman-Petersen-Gillum Group characterizes hormones and metabolites generated via the gut, gut microbiota, and liver that govern host metabolism and appetite. We identify the receptors and cellular targets through which they exert their beneficial or detrimental effects with the goal of identifying novel therapeutic possibilities.

See also Professor Gerald Shulmans and Professor Kitt Petersens research profiles at Yale School of Medicine.

Research focus

The overarching hypothesis is that the liver, gut, and gut microbiome affects host metabolism through the production of key metabolites and hormones which enter the body to act on target proteins or receptors expressed in endocrine and metabolic organs of the host. The current challenge is to move beyond descriptive studies and identify the mechanism by which the liver, gut, and gut microbiota contribute to host metabolism, appetite and the development of metabolic disease.

The Shulman-Petersen-Gillum Group characterizes identified metabolites generated via the gut microbiota, gut, and liver that affect host metabolism and appetite. We identify the receptors and cellular targets through which they exert their beneficial or detrimental effects. Identifying such metabolite receptor pairs may provide novel therapeutic possibilities by either targeting metabolite synthesis or developing receptor agonists/antagonists. We anticipate to find several unidentified microbial metabolites that could affect host metabolism, as well as hepatic factors that regulate appetite.

Main findings

“FGF21 Is a Sugar-Induced Hormone Associated with Sweet Intake and Preference in Humans”
Published in Cell Metabolism in 2017 this study identifies variation near the hepatokine fibroblast growth factor 21 (FGF21) in relation to food intake, especially sugar-containing items in Danish individuals. The findings suggest that the liver may secrete hormones that influence eating behavior.

“FGF21 Mediates Endocrine Control of Simple Sugar Intake and Sweet Taste Preference by the Liver”
Published in Cell Metabolism in 2016 this study shows that the liver regulates carbohydrate intake through production of the hepatokine fibroblast growth factor 21 (FGF21), which markedly suppresses consumption of simple sugars, but not complex carbohydrates, proteins, or lipids.

“Central serotonergic neurons activate and recruit thermogenic brown and beige fat and regulate glucose and lipid homeostasis”
Published in Cell Metabolism in 2015 this study uses generated mice in which the human diphtheria toxin receptor is selectively expressed in central serotonin neurons to show how the neurons play a major role in regulating glucose and lipid homeostasis, in part through recruitment and metabolic activation of brown and beige adipocytes.

Staff of the Shulman-Petersen-Gillum Group

Group leader: Associate Professor Matthew Gillum