Research

Our laboratory investigates the roles of peroxisomal lipid metabolism in energy homeostasis and metabolic disease. Current areas of research include:

 

UCP1-Independent Thermogenesis

Adaptive thermogenesis is traditionally attributed to mitochondrial uncoupling protein 1 (UCP1) in brown and beige adipose tissue. However, mammals can also generate heat through UCP1-independent mechanisms.

 

Our laboratory discovered a peroxisome-dependent pathway of UCP1-independent thermogenesis involving the synthesis and oxidation of branched-chain fatty acids. In this pathway, fatty acids are synthesized using ATP and subsequently oxidized by the peroxisomal enzyme ACOX2, creating a futile metabolic cycle that dissipates energy as heat. Increasing ACOX2 activity in adipose tissue enhances thermogenesis and protects against diet-induced obesity, even in the absence of UCP1.

​

These findings identify peroxisomes as an important site of adaptive heat production and reveal an unexpected connection between lipid metabolism and energy expenditure. We are investigating the molecular and physiological regulation of this pathway and its potential relevance to obesity and metabolic disease.

.

Peroxisome–Mitochondria Crosstalk

We study how peroxisomes influence mitochondrial function. Our work has shown that peroxisomal lipid metabolism regulates mitochondrial membrane composition, dynamics, and thermogenic function, revealing multiple mechanisms of communication between these organelles.

 

Peroxisomal Lipid Signaling

We investigate how peroxisomal metabolism generates bioactive lipids that act as metabolic signals. Our studies demonstrated that loss of hepatic ACOX1 increases very-long-chain omega-3 fatty acids that signal through GPR120 to promote adipose tissue browning and improve systemic metabolism.

 

Ether Lipids and Plasmalogens

Peroxisomes are required for the synthesis of ether lipids, including plasmalogens. Our work has shown that disruption of adipose peroxisomal function reduces mitochondrial plasmalogens and impairs mitochondrial function and adaptive thermogenesis. We study how ether lipid metabolism contributes to organelle and tissue physiology.

Peroxisomal Metabolism in Metabolic Disease

 

We investigate how alterations in peroxisomal lipid metabolism contribute to obesity, diabetes, fatty liver disease, and cardiovascular disease, with the goal of identifying metabolic pathways that may provide new opportunities for therapeutic intervention.