Activation of AMPK-Regulated CRH Neurons in the PVH is Sufficient and Necessary to Induce Dietary Preference for Carbohydrate over Fat

Food selection is essential for metabolic homeostasis and is influenced by nutritional state, food palatability, and social factors such as stress. However, the mechanism responsible for selection between a high-carbohydrate diet (HCD) and a high-fat diet (HFD) remains unknown. Here, we show that ac...

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Veröffentlicht in:Cell reports (Cambridge) Jg. 22; H. 3; S. 706 - 721
Hauptverfasser: Okamoto, Shiki, Sato, Tatsuya, Tateyama, Michihiro, Kageyama, Haruaki, Maejima, Yuko, Nakata, Masanori, Hirako, Satoshi, Matsuo, Takashi, Kyaw, Sanda, Shiuchi, Tetsuya, Toda, Chitoku, Sedbazar, Udval, Saito, Kumiko, Asgar, Nur Farehan, Zhang, Boyang, Yokota, Shigefumi, Kobayashi, Kenta, Foufelle, Fabienne, Ferré, Pascal, Nakazato, Masamitsu, Masuzaki, Hiroaki, Shioda, Seiji, Yada, Toshihiko, Kahn, Barbara B., Minokoshi, Yasuhiko
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States Elsevier Inc 16.01.2018
Elsevier
Schlagworte:
AMP-Activated Protein Kinases - metabolism
AMPK
Animals
Carbohydrates
Corticotropin-Releasing Hormone - metabolism
CPT1c
CRH
Diet
food preference
Male
Mice
Neurons - physiology
PVH
CRH
AMPK
food preference
PVH
CPT1c
ISSN:2211-1247, 2211-1247
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Zusammenfassung:Food selection is essential for metabolic homeostasis and is influenced by nutritional state, food palatability, and social factors such as stress. However, the mechanism responsible for selection between a high-carbohydrate diet (HCD) and a high-fat diet (HFD) remains unknown. Here, we show that activation of a subset of corticotropin-releasing hormone (CRH)-positive neurons in the rostral region of the paraventricular hypothalamus (PVH) induces selection of an HCD over an HFD in mice during refeeding after fasting, resulting in a rapid recovery from the change in ketone metabolism. These neurons manifest activation of AMP-activated protein kinase (AMPK) during food deprivation, and this activation is necessary and sufficient for selection of an HCD over an HFD. Furthermore, this effect is mediated by carnitine palmitoyltransferase 1c (CPT1c). Thus, our results identify the specific neurons and intracellular signaling pathway responsible for regulation of the complex behavior of selection between an HCD and an HFD. [Display omitted] [Display omitted] •AMPK in a subset of CRH neurons in the PVH is preferentially activated by fasting•AMPK activation in CRH neurons promotes selection of carbohydrates over fat•CPT1c in CRH neurons is necessary for AMPK- or fasting-induced carbohydrate selection•Carbohydrate feeding after fasting quickly decreases plasma ketone body levels Food selection is influenced by nutritional state as well as food palatability. However, the mechanism remains unknown. Okamoto et al. find that activation of an AMPK-CPT1c pathway in a subset of CRH-positive neurons in the paraventricular hypothalamus mediates the fasting-induced increase in high-carbohydrate diet selection.
Bibliographie:ObjectType-Article-1
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content type line 23
ISSN:2211-1247
2211-1247
DOI:10.1016/j.celrep.2017.11.102