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. A fundamental concept in understanding obesity is energy balance; obesity develops when energy intake (i.e., feeding) chronically exceeds total energy expenditure.
Adipose tissue serves as a central regulator of energy balance. 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 in rodents and humans. The main focus of our lab is to uncover the molecular circuits that control brown and white fat cell development and their roles in energy metabolism.
Over the last several years, we have been studying the transcriptional regulation of brown fat development. As an example, we have defined key transcriptional regulators, such as PRDM16 (PR-domain containing 16), C/EBPβ, and EHMT1 that determines the cellular fate of brown and beige adipocytes. By employing a wide range of molecular biology, developmental biology, and biochemical/pharmacological approaches, we aim to engineer adipose cell fate and generate energy-burning brown/beige adipocytes in vivo. We hope these studies lead to the development of novel therapeutic interventions for obesity and obesity-related metabolic diseases, such as type 2 diabetes.
Shinoda K., Luijten I. H.N., Hasegawa Y., Hong H., Sonne S. B., Xue R., Chondronikola M., Kim M., Cypess A.M., Tseng Y., Nedergaard J., Sidossis L.S., and Kajimura S. (2015). Genetic and functional characterization of clonally-derived adult human brown adipocytes. Nature Medicine 21(4):389-394
Galmozzi A., Sonne S.B., Keylin S., Hasegawa Y., Shinoda K., Luijten I., Chang J.W., Sharp L.Z., Cravatt B. F., Saez E., and Kajimura S. (2014). ThermoMouse: an in vivo model to identify modulators of UCP1 expression in brown adipose tissue. Cell Reports S2211-1247. (Selected in Faculty1000)
Ohno, H., Shinoda, K., Ohyama, K., Sharp, L.Z. & Kajimura, S. (2013). EHMT1 controls brown adipose cell fate and thermogenesis through the PRDM16 complex. Nature 504(7478):163-7. PMC3855638 (Selected in Faculty1000)
Ohno H, Shinoda K, Spiegelman BM, Kajimura S. PPARγ agonists induce a white-to-brown fat conversion through stabilization of PRDM16 protein. Cell Metabolism 2012, 15(3):395-404.
Kajimura S., Seale P., Kubota K., Lunsford E., Frangioni J.V., Gygi S.P., and Spiegelman B.M. Initiation of myoblast to brown fat switch by a PRDM16-C/EBP-β transcriptional complex. Nature 2009, 460(7259): 1154-1158. (Selected in Faculty1000)