Metabolism, Obesity, and Metabolic Diseases

Obesity has become an important cause of cardiovascular disease, either directly or through metabolic complications like type-2 diabetes. Obesity can be caused by abnormalities in the way the brain controls energy intake and metabolism and by changes in the fat cells themselves.

Scientists studying metabolism, obesity, and metabolic disease focus on the genetics, cell biology, and physiology of metabolism and obesity and on how metabolic syndromes cause cardiovascular disease.

Molecular and cell biologists collaborate with physiologists to determine how peripheral hormones such as insulin or the fat cell-derived hormone leptin act on the brain to control energy intake. Characterization of the brain’s effectors of these hormones has already led to description of genetic alterations that can cause human obesity and to new therapeutic targets for obesity. Collaborations with geneticists will determine the extent to which common obesity might be caused by subtle mutations in genes involved in dramatic familial obesity syndromes.

Surprisingly, hormones are still being discovered that regulate how cells respond to insulin and how and where energy is stored. Molecular and cell biologists working to identify new hormones will test their ideas by interacting with animal modelers and geneticists. Collaborations with molecular imaging experts will enable visualization of metabolic processes in both animals and humans, permitting rapid translation of findings in model systems to humans and accelerating the development of metabolic therapies in patients.

Investigators also focus on lipoprotein abnormalities. Elevated blood levels of these particles, which transport fat, are a common cause of atherosclerosis. Biochemists studying the mechanisms by which lipoproteins are produced and cleared interact with geneticists using candidate-based and genome-wide association studies to identify genes that underlie lipid disorders in human beings. They also work with model organism experts to study the detailed mechanisms by which mutations in these genes cause disease, and collaborations with chemists and cell biologists will help elucidate the connection between elevated lipoprotein levels and plaque formation.