Voglibose-mediated alterations in neurometabolomic profiles in the hypothalamus of high-fat diet-fed mice

Abstract

The alpha-glucosidase inhibitor voglibose (VO) was recently reported to have a protective effect against weight gain as well as affect various metabolic changes related to food intake and gut–brain signaling. We hypothesized that VO prevents weight gain by altering neurometabolome profiles in the hypothalamus to reduce food intake. To test this hypothesis, we assessed metabolite profiles in the hypothalamus of standard diet- or high-fat (HF) diet-fed mice in the absence or presence of VO. In total, 29 male C57BL/6 mice were divided into 3 groups: (1) lean control, (2) HF, and (3) HF + VO. Vehicle or VO was administered for 12 weeks. The results showed that there were alterations in levels of metabolites across several metabolic pathways in the hypothalamus. VO treatment increased levels of many amino acids including arginine, glutamine, histidine, isoleucine, leucine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine in the hypothalamus. In addition, levels of 2-hydroxy-2-methyl-butyric acid in the hypothalamus were significantly increased after VO administration in HF diet-fed mice. Among lipid metabolites, levels of fatty acids were higher in the hypothalamus of VO-treated mice than in that of HF diet-fed mice. In terms of the energy status, the ATP/ADP ratio was higher in the hypothalamus of VO-treated mice (P < 0.001), thereby indicating an energy surplus. In conclusion, VO supplementation altered metabolite profiles in the hypothalamus to enhance catabolism, which is possibly responsible for the hypophagic effect of VO in HF diet-fed mice.

Keywords:

• Voglibose
• Hypothalamus
• Metabolomics
• Food intake
• ATP/ADP ratio
• 2-Hydroxy-2-methyl-butyric acid

ORCID

Soo Jin Yang http://orcid.org/0000-0001-7892-7648

Min-Jeong Shin http://orcid.org/0000-0002-8952-4008