We study nutrient sensing and energy homeostasis

All animals consume nutrients, convert those nutrients into energy, and use that energy to sustain life. But nutrient availability and metabolic demand are constantly changing. This leads to several fundamental questions in organismal energy homeostasis and physiology: How does the body sense changes in nutrient and energy status? How are those signals converted into downstream effectors? And how do these effectors regulate feeding behavior, energy expenditure, and systemic metabolic homeostasis?

Our laboratory seeks to answer these questions by defining the molecular mechanisms that control nutrient sensing and energy homeostasis in cells, animal models, and humans. This investigative program builds on and extends work in the classical fields of biochemistry and endocrinology, but with important technology advantages enabled by the availability of modern high-resolution genetic and analytical approaches. In the long term, our goal is to translate our discoveries into therapeutic opportunities for diseases of energy metabolism, including obesity, diabetes, dyslipidemia, sarcopenia, cachexia, and age-associated chronic disease.

Our current research interests are described below.

Exercise

Physical activity has broad salutary effects, but the molecular signals downstream of exercise remain poorly defined. We discovered that exercise induces production of a lactate metabolite called Lac-Phe that suppresses feeding and body weight after exercise. Lac-Phe production is mediated by gut enterocyte CNDP2+ cells. Lac-Phe levels are increased by metformin and mediates metformin-associated weight loss. A similar pathway occurs during ketosis to generate a Lac-Phe congener called BHB-Phe. We are now uncovering additional genetic and biochemical regulators of these and other exercise-regulated metabolites, as well as their downstream mechanisms of action.

Moya-Garzon et al., Cell 2025; Xiao et al., Nat. Metab. 2024; Li et al. Nat. Commun. 2024; Li et al., Nature 2022

Nutrients

Despite the important role of diet and nutrition in metabolic health, our understanding of how what we eat influences our physiology and health remains limited. We recently uncovered a link between dietary taurine consumption and body weight by showing that the previously orphan body mass index-associated enzyme called PTER mediates catabolism of the anorexigenic metabolite N-acetyltaurine. First-in-class chemical PTER inhibitors are now being evaluated in pre-clinical studies. We are also using feast-or-famine animals, such as the Burmese python, to uncover how extremely eating patterns affect metabolism and physiology.

Xiao et al. Nat. Metab. 2026; Fu et al. Cell Chem. Biol. 2026; Wei et al. Nature 2024

Lipids

We have had a longstanding interest in the biochemistry, enzymology, and signaling of lipid metabolites. Our work here focuses on a family of lipid metabolites called N-acyl amino acids that stimulate mitochondrial respiration in vitro and energy expenditure in vivo. Levels of N-acyl amino acids are under tight enzymatic and genetic regulation, including by PM20D1, FAAH, and CY4F enzymes. Polymorphisms in enzymatic pathways of N-acyl amino acid metabolism are linked to human body mass index, thereby connecting this lipid pathway to human obesity. We are now uncovering additional molecules that control N-acyl amino acid function in mouse and human energy homeostasis.

Tanzo et al. J Biol Chem. 2023; Li et al. Diabetes 2020; Kim et al., Cell Chem Biol. 2020; Kim et al., eLife 2020; Long et al., PNAS 2018; Long et al., Cell 2016

Technology

Complementing the focused studies outlined above, we are developing new mass spectrometry-based technologies for mapping the chemical composition of blood plasma. A long-term goal for these technologies is to enable cell-type specific manipulation of the plasma proteome and metabolome following dynamic energy stressors such as nutrient availability, physical activity, or environmental temperature changes. Currently, we are developing new technologies for systematic profiling of secreted polypeptides, metabolites, and exosomes.

Wiggenhorn et al, Nat. Commun. 2023; Wei et al. Cell Met. 2023; Wei et al., Nat. Chem. Biol. 2020; Kim et al., Cell Chem. Biol. 2019