HOME >  Research >  Division of Endocrinology and Metabolism

Research

Division of Endocrinology and Metabolism

WebSite

Member

Molecular mechanism for the hypothalamic regulation of whole body energy metabolism
Physiological and pathophysiological roles of AMPK in whole body metabolism

  The animal body has an integrated-regulatory system for “homeostasis” that maintains a normal, constant internal state by responding to changes in both the external and internal environments. Within the central nervous system, the hypothalamus is a crucial center that regulates the homeostatic activities by integrating autonomic nervous system, endocrine system and immune function. This division is investigating the role of hypothalamus in body energy balance in mammals. The main subjects of our current research are as follows:

(1) Molecular mechanism of the hypothalamic regulation of food intake and glucose and lipid metabolism.
(2) Signaling pathway for metabolic action of leptin, adipokines and myokines.
(3) Physiological and pathophysiological roles of AMPK in whole body metabolism.
(4) Development of novel analytical method for glucose and lipid metabolism.

 

2017minokoshi-1.jpg

Fig. 1 Leptin controls body energy metabolism by reciprocally regulating AMP kinase in the hypothalamus and skeletal muscle.
Leptin activates AMP kinase(AMPK) in skeletal muscle directly at the muscle level and indirectly through the hypothalamicsympathetic nervous system. Leptin also inhibits food intake by suppressing AMPK activity in the hypothalamus.
Reciprocal regualtion of AMPK activity in the hypothalamus and skeletal muscle is necessary for the leptin’s effect on energy metabolism. We are studying the molecular
mechanism for the reciprocal regulation of AMPK activity in the hypothalamus and skeletal muscle.

 

2017minokoshi-2.jpg

Fig.2 Sympathetic nerve activity maintains an anti- in ammatory state in adipose tissue in mice byinhibiting TNF- α gene expression in macrophages.
Adipose tissue macrophages(ATMs)play an important role in the in ammatory response in animals. We found that brain AgRP and sympathetic nervous system(SNS)are necessary to maintain the abundance of the mRNA for the proin ammatory cytokine TNF- α at a low level in ATMs of lean mice.

Typical paper information

*Y. Minokoshi, et al., Nature 415, 339, 2002.
*Y. Minokoshi, et al., Nature 428, 569, 2004.
*T. Shiuchi, et al., Cell Metab 10, 466, 2009.
*C. Toda, et al., Diabetes 62, 2295, 2013.
*L. Tang, et al., Endocrinology 156, 3680, 2015.
Researchers List

Introduce a researcher of NIPS.