Shingo Kajimura, Ph.D.

Molecular Basis of Fat Cell Development and Energy Homeostasis

Obesity is a major risk factor for metabolic disorders such as type-2 diabetes and cardiovascular disease. Adipose tissues serve as central regulators of energy homeostasis in response to a variety of environmental and genetic factors, by systemic signaling via secretion of various adipokines, and by adaptive thermogenesis. The main focus of our lab is to uncover the molecular circuits that control fat cell development and function by employing a wide range of molecular biology, developmental biology and biochemical approaches together with mouse genetics.

Two types of adipose tissue, white and brown, are found in mammals: white adipose tissue (WAT) functions exclusively in the storage of excess energy, while brown adipose tissue (BAT) is specialized to dissipate chemical energy in the form of heat through a process called non-shivering thermogenesis. Due to its remarkable oxidative capacity to dissipate excess chemical energy, brown fat function is tightly linked to the development of obesity and metabolic disorders.  Since recent studies clearly demonstrated the existence of significant deposits of active BAT in adult humans, altering the amount and activity of BAT could provide a novel therapeutic intervention to counteract obesity and metabolic syndrome.

Over the last several years, we have been studying the transcriptional regulation of brown fat development. We have recently defined PRDM16 (PR-domain containing 16) and C/EBPβ as a critical transcriptional unit that determines the cellular fate of brown fat. Significantly, ectopic expression of the two factors is sufficient to reconstitute a fully functional brown fat program in naïve fibroblastic cells, from mouse and man, in vivo.

Our goal is to further decode the transcriptional and epigenetic regulatory networks that govern fate determination and maintenance of brown fat cells, and to investigate their roles in controlling whole body energy metabolism under physiological and pathological conditions such as obesity. We hope these studies have applications to the development of novel therapies for obesity, insulin resistance and metabolic diseases.

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