GLP-1 release and vagal afferent activation mediate the beneficial metabolic and chronotherapeutic effects of D-allulose.

Abstract	Overeating and arrhythmic feeding promote obesity and diabetes. Glucagon-like peptide-1 receptor (GLP-1R) agonists are effective anti-obesity drugs but their use is limited by side effects. Here we show that oral administration of the non-calorie sweetener, rare sugar D-allulose (D-psicose), induces GLP-1 release, activates vagal afferent signaling, reduces food intake and promotes glucose tolerance in healthy and obese-diabetic animal models. Subchronic D-allulose administered at the light period (LP) onset ameliorates LP-specific hyperphagia, visceral obesity, and glucose intolerance. These effects are blunted by vagotomy or pharmacological GLP-1R blockade, and by genetic inactivation of GLP-1R signaling in whole body or selectively in vagal afferents. Our results identify D-allulose as prominent GLP-1 releaser that acts via vagal afferents to restrict feeding and hyperglycemia. Furthermore, when administered in a time-specific manner, chronic D-allulose corrects arrhythmic overeating, obesity and diabetes, suggesting that chronotherapeutic modulation of vagal afferent GLP-1R signaling may aid in treating metabolic disorders.
Authors	Yusaku Iwasaki, Mio Sendo, Katsuya Dezaki, Tohru Hira, Takehiro Sato, Masanori Nakata, Chayon Goswami, Ryohei Aoki, Takeshi Arai, Parmila Kumari, Masaki Hayakawa, Chiaki Masuda, Takashi Okada, Hiroshi Hara, Daniel J Drucker, Yuichiro Yamada, Masaaki Tokuda, Toshihiko Yada
Journal	Nature communications (Nat Commun) Vol. 9 Issue 1 Pg. 113 (01 09 2018) ISSN: 2041-1723 [Electronic] England
PMID	29317623 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Anti-Obesity Agents Blood Glucose Glp1r protein, mouse Glucagon-Like Peptide-1 Receptor psicose Fructose
Topics	Animals Anti-Obesity Agents (pharmacology) Blood Glucose (drug effects) Eating (drug effects) Fructose (pharmacology) Glucagon-Like Peptide-1 Receptor (agonists, genetics, metabolism) Glucose Intolerance (drug therapy) Hyperphagia (drug therapy) Male Mice Mice, Inbred C57BL Mice, Knockout Obesity (drug therapy) Rats Rats, Wistar Vagus Nerve (drug effects, metabolism)

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