It is possible that regulation of adiposity

It is possible that regulation of adiposity and glucose homeostasis by GIP are in part mediated by altering leptin levels and/or leptin signaling. However, we are unaware of reports that support this mechanism of action of GIP. In addition, leptin levels in GIP receptor knockout mice [12], [52] and mice with ablation of K-cells [20] remained proportional to fat mass, suggesting that GIP action does not directly regulate leptin production. The concept of an adipo–enteroendocrine axis has been proposed, based upon observations that leptin directly stimulates GLP-1 secretion from rodent and human intestinal L house [53], but whether leptin regulates GIP secretion from K-cells is unknown. Our mouse model enabled us to investigate the impact of GIP deficiency independent of leptin signaling. Collectively, our findings suggest diploid endogenous GIP is not involved in the development of obesity in mice with complete absence of leptin.
Disclosure statement This study was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan Society for the Promotion of Science (JSPS), Ministry of Health, Labour, and Welfare, Ministry of Agriculture, Forestry and Fisheries, Japan Diabetes Foundation, Japan Association for Diabetes Education and Care, Merck Sharp & Dohme (MSD) Life Science Foundation, and Public Interest Incorporated Foundation, Japan Diabetes Foundation, Suzuken Memorial Foundation.
Acknowledgments