Glucose‐dependent insulinotropic polypeptide monoclonal antibodies prevent and treat obesity in wild‐type and hyperphagic mice

Abstract

Objective This study aimed to investigate whether a glucose‐dependent insulinotropic polypeptide (GIP) monoclonal antibody (mAb) will promote weight loss in wild‐type mice and to determine effects of this mAb in preventing weight gain in ob/ob mice. Methods Phosphate‐buffered saline (PBS) or GIP mAb was injected intraperitoneally to wild‐type mice fed a 60% high‐fat diet (HFD). After 12 weeks, mice that received PBS were divided into two groups and were fed a 37% HFD for 5 weeks; one group received PBS, and one group received GIP mAb. In a separate study, PBS or GIP mAb was injected intraperitoneally to ob/ob mice fed normal mouse chow for 8 weeks. Results PBS‐treated mice gained significantly more than those treated with GIP mAb, with no difference in food consumption detected. Obese mice fed a 37% HFD and PBS continued to gain weight (+2.1% ± 0.9%), whereas mice administered GIP mAb lost 4.1% ± 1.4% body weight (p < 0.01). Leptin‐deficient mice consumed similar amounts of chow, and, after 8 weeks, the PBS‐ and GIP mAb‐treated mice gained 250.4% ± 9.1% and 192.4% ± 7.3%, respectively (p < 0.01). Conclusions These studies support the hypothesis that a reduction in GIP signaling appears to affect body weight without suppressing food intake and might provide a novel, useful method for the treatment and prevention of obesity.

Does glucose-dependent insulinotropic polypeptide receptor blockade as well as agonism have a role to play in management of obesity and diabetes?

“…A number of studies have indicated that immunisation against GIP peptides, as a means to stimulate active endogenous antibody generation, is an efficacious method of improving obesity-diabetes in rodents [Fulurija et al 2008;Irwin et al 2009;Montgomery et al 2010;Wolfe et al 2023], although suitability of this approach in humans is yet to be determined. Indeed, given the various important physiological actions of GIP [Figure 1], it may be anticipated that side-effects could occur with this approach.…”