Abstract

While a low-fat diet and regular exercise are popular approaches to combat obesity, one easy alternative is simply to increase energy metabolism. Employing a synthetic biology approach, we are working to create an artificial futile cycle in mammalian liver cells by introducing glyoxylate enzymes native to bacteria. Past research has shown that mice expressing enzymes facilitating an active glyoxylate shunt are resistant to diet-induced obesity. Our team plans to introduce an inducible system that allows us to couple the sensing of circulating fatty acid concentrations with a circuit of glyoxylate shunt. Our inducible system is intended to prevent the risk of fatty acid deficiency, while facilitating greater fatty acid uptake at higher fatty acid circulating concentrations. Such a system should increase the feasibility of a glyoxylate cycle engineered to function in vivo.