Division of Diabetes and Nutrition

Summary

The aims of our studies are to determine unveiling endocrine and metabolic pathways, which may be useful to stop obesity and diabetes. Since 1998, we have investigated central serotonin (5-HT) network via 5-HT2C receptor in appetite regulation and energy homeostasis (1). Recently, our research target has been moved to tryptophan metabolites and peripheral 5-HT system. We found that intake of whey protein suppresses hepatic bile acids (BAs), plasma 5-HT and insulin levels in mice fed a chow diet, whereas intake of a soy protein, β-conglycinin, increased them (2). Thus, we found a novel feeding-dependent hormonal network among BAs, 5-HT, and insulin.

Moreover, we found that administration of GLP-1 receptor agonist liraglutide decreases BAs, especially in the primary BAs, tryptophan, 5-HT, and kynurenine in the colon, and plasma 5-HT and insulin levels in mice deprived of food (3). On the other hand, liraglutide increases plasma FGF21 levels and indolepropionic acid (IPA), a tryptophan metabolite, in the colon (3). Moreover, liraglutide acutely decreases blood glucose levels and body weight independently of feeding (3). From these findings, we suggest that we have a novel feeding-independent hormonal network among GLP-1, BAs, tryptophan metabolites including 5-HT and IPA, and insulin. We will further determine the feeding-dependent and -independent hormonal networks in the regulation of glucose metabolism and body weight.

Key words

diabetes, obesity, 5-HT, GLP-1, FGF21, bile acids, tryptophan metabolism

References

  1. Nonogaki K. Int J Mol Sci. 2022 Jan 29;23(3):1600.
  2. Nonogaki K et al. Front Endocrinol (Lausanne). 2023 Jan 27;14:1080790.
  3. Nonogaki K et al. Int J Mol Sci. 2024 Jul 16;25(14):7784.

Staff

Professor　Katsunori Nonogaki MD, PhD

Assistant Professor　Takao Kaji PhD