title: Involvement of brain ketone bodies and the noradrenergic pathway in diabetic hyperphagia in rats.
abstract: Uncontrolled type 1 diabetes leads to hyperphagia and severe ketosis. This study was conducted to test the hypothesis that ketone bodies act on the hindbrain as a starvation signal to induce diabetic hyperphagia. Injection of an inhibitor of monocarboxylate transporter 1, a ketone body transporter, into the fourth ventricle normalized the increase in food intake in streptozotocin (STZ)-induced diabetic rats. Blockade of catecholamine synthesis in the hypothalamic paraventricular nucleus (PVN) also restored food intake to normal levels in diabetic animals. On the other hand, hindbrain injection of the ketone body induced feeding, hyperglycemia, and fatty acid mobilization via increased sympathetic activity and also norepinephrine release in the PVN. This result provides evidence that hyperphagia in STZ-induced type 1 diabetes is signaled by a ketone body sensed in the hindbrain, and mediated by noradrenergic inputs to the PVN.
authors.affiliation: Laboratory for Reproductive Science, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8601, Japan.
authors.forename: Kinuyo
authors.initials: K
authors.lastname: Iwata
authors.forename: Mika
authors.initials: M
authors.lastname: Kinoshita
authors.forename: Shunji
authors.initials: S
authors.lastname: Yamada
authors.forename: Takuya
authors.initials: T
authors.lastname: Imamura
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Uenoyama
authors.forename: Hiroko
authors.initials: H
authors.lastname: Tsukamura
authors.forename: Kei-Ichiro
authors.initials: K
authors.lastname: Maeda
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002395:Catecholamines / Q000037:antagonists & inhibitors / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004435:Eating; D004734:Energy Metabolism / Q000502:physiology; D004805:Ependyma / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D006943:Hyperglycemia / Q000378:metabolism; D006963:Hyperphagia / Q000378:metabolism*; D007657:Ketone Bodies / Q000378:metabolism*; D008297:Male; D027501:Monocarboxylic Acid Transporters / Q000037:antagonists & inhibitors / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012249:Rhombencephalon / Q000378:metabolism*; D013217:Starvation / Q000378:metabolism; D027981:Symporters / Q000037:antagonists & inhibitors / Q000378:metabolism; D000099233:Monocarboxylate Transport Protein 1
chemical_list: D001786:Blood Glucose; D002395:Catecholamines; D005227:Fatty Acids; D007657:Ketone Bodies; D027501:Monocarboxylic Acid Transporters; D009638:Norepinephrine; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1