D-Allulose cooperates with glucagon-like peptide-1 and activates proopiomelanocortin neurons in the arcuate nucleus and central injection inhibits feeding in mice

• Published in: Biochemical and biophysical research communications 2022-07, Vol.613, p.159-165
• Main Authors: Yermek, Rakhat, Wang, Lei, Kaneko, Kentaro, Han, Wanxin, Seino, Yutaka, Yabe, Daisuke, Yada, Toshihiko
• Format: Article
• Language: English
• Subjects: Arcuate nucleus; Cytosolic Ca2; D-Allulose; Diabetes; Food intake; Glucagon-like peptide-1; Obesity; Proopiomelanocortin neurons
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2022.04.027

A rare sugar D-Allulose has sweetness without calorie. Previous studies have shown that D-Allulose improves glucose and energy metabolism and ameliorates obesity. However, underlying mechanisms remain elusive. This study explored the effect of central injection of D-Allulose on feeding behavior in mice. We also examined direct effects of D-Allulose on the neurons in the hypothalamic arcuate nucleus (ARC) that regulate feeding, including the anorexigenic glucagon-like peptide-1 (GLP-1)-responsive neurons and proopiomelanocortin (POMC) neurons. Single neurons were isolated from ARC and cytosolic Ca2+ concentration ([Ca2+]i) was measured by fura-2 microfluorometry. Administration of D-Allulose at 5.6, 16.7 and 56 mM concentration-dependently increased [Ca2+]i in ARC neurons. The [Ca2+]i increases took place similarly when the osmolarity of superfusion solution was kept constant. The majority (40%) of the D-Allulose-responsive neurons also responded to GLP-1 with [Ca2+]i increases. D-Allulose increased [Ca2+]i in 33% of POMC neurons in ARC. D-Allulose potentiated the GLP-1 action to increase [Ca2+]i in ARC neurons including POMC neurons. Intracerebroventricular injection of D-Allulose significantly decreased food intake at 1 and 2 h after injection. These results demonstrate that D-Allulose cooperates with glucagon-like peptide-1 and activates the ARC neurons including POMC neurons. Furthermore, central injection of D-Allulose inhibits feeding. These central actions of D-Allulose may underlie the ability of D-Allulose to counteract obesity and diabetes. •Central injection of Allulose rapidly inhibits food intake at 1-2 h after injection.•Allulose activates the arcuate nucleus (ARC) POMC neurons by increasing [Ca2⁺]i.•Allulose activates the ARC neurons that respond to glucagon-like peptide-1 (GLP-1).•Allulose potentiates the ability of GLP-1 to activate ARC neurons and POMC neurons.•This neuronal activation underlies acute anorexigenic action of central D-Allulose.