Ketosis-inducible metabolite as a therapeutic for obesity and/or related metabolic diseases

Researchers at Stanford University have identified a natural metabolite that is induced in ketosis and functions to suppress food intake and lower body weight. Pharmacological treatment with the metabolite offers a strategy for treatment of obesity and related metabolic disorders.

Ketosis is a physiological state in which fats are used for metabolic fuel due to a low availability of carbohydrates. Ketosis can be induced by prolonged exercise, starvation, or low carbohydrate intake, such as in a ketogenic diet. Recently, there has been considerable interest in exploiting ketosis for its beneficial effects in glucose homeostasis and weight loss, and for treatment of related metabolic disorders. However, most current strategies strive to induce ketosis by behavioral interventions, such as diet and exercise. Pharmacological interventions that induce or mimic ketosis would offer a complementary strategy to existing weight loss tools.

In this technology, Stanford researchers have discovered a metabolite that is naturally elevated in ketosis in mice and humans. Genetic knockout of the metabolite biosynthesis in mice on a ketogenic diet increases food intake and body weight, and worsens glucose homeostasis compared to wild type mice. Importantly, exogenous treatment with the metabolite in mouse models suppresses food intake without impacting ambulatory activity, thus reducing body weight and improving glucose homeostasis. Accordingly, pharmacological delivery of the metabolite or derivatives offers a promising method for the treatment of obesity, diabetes, and related metabolic disorders.

Stage of Development
In vivo data