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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.

 

2018minokoshi-1ENG.jpg

Fig. 1 Effects of activation of SF1/Ad4BP neuron by DREADD technology on energy metabolism in mice. Specific activation of SF1 neurons inhibits food intake and increases energy expenditure. In addition, activation of these neurons increases insulin sensitivity and glucose uptake in some peripheral tissues such as skeletal muscle.

 

2018minokoshi-2ENG.jpg

Fig.2 Discovery of neurons that induce selection of carbohydrate over fat.
AMP kinase-regualted CRH neurons in the PVH is necessary and sufficient to inducse selection of carbohydrate over fat after fasting.
 

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.
*E.A. Coutinho, et al., Diabetes 66, 2372, 2017.
*S. Okamoto, et al., Cell Reports 22, 706, 2018.
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