Pharmacologic approaches to the treatment of obesity

National Institute Of Diabetes And Digestive And Kidney Diseases

Investigators

Linked publications, trials & patents

Abstract

Summary: Obesity is a huge and increasing medical problem, with inadequate therapeutic options. One approach to the treatment of obesity is long-term pharmacotherapy. Drugs currently approved in the United States include orlistat, phentermine/topiramate, buproprion/naltrexone, setmelanotide, liraglutide, and semaglutide. The limited efficacy of single agents has led to the idea that additional agents and combination therapy are required. Progress in FY2022-23 includes the following: Mice are not simply small humans. Because mice are used widely to study diabetes and obesity, understanding their thermal biology is critical to translating observations from mice to humans. In humans, the heat needed to maintain body temperature is virtually all created as a byproduct of metabolic processes. People generally live in a thermoneutral zone, a 10C range of ambient temperatures over which core body temperature is maintained without increasing metabolic rate. In contrast, mice typically live below thermoneutrality. At room temperature (20-22C) about half of food intake is used to generate heat. We are undertaking a range of quantitative analyses to understand the contributors to mouse energy expenditure. These results inform how mice can be used to model human obesity physiology and drug development. We are currently using this new knowledge about thermoneutrality in mice to explore its implications in energy homeostasis.