Researchers at WashU Medicine have uncovered a new pathway in brown fat cells involving the enzyme ACOX2, which can boost heat production and potentially improve metabolic health in mice.

This process involves the protein ACOX2 in peroxisomes, cellular compartments that process fats, and is especially active when mitochondria are deficient or during cold exposure, leading to increased thermogenesis.

Mice lacking ACOX2 exhibit reduced cold tolerance, lower insulin sensitivity, and greater obesity when fed high-fat diets, highlighting the enzyme's crucial role in metabolic regulation.

The findings, published today in Nature by Liu, X. et al., provide new insights into fat cell metabolism and the mechanisms behind thermogenesis.

Supported by NIH and European funding, the researchers have filed a provisional patent targeting ACOX2 activation as a potential treatment for obesity and metabolic diseases.

This research opens up new possibilities for treating metabolic disorders by exploring the functions of peroxisomes in heat production.

The study also links lipogenesis to thermogenesis, showing that enzymes like FASN promote the synthesis of monomethyl branched-chain fatty acids (mBCFAs), which are involved in heat generation.

During thermogenic stimuli, the activity and localization of FASN and ACOX2 to peroxisomes increase, facilitating the synthesis and breakdown of mBCFAs to produce heat.