GIP exerts its function through its specific receptor, GIPR. Inactivation of GIPR results in a defective GIP signaling [15]. Under normal diet, GIPR knockout mice (Gipr-/-) do not exhibit changes in body weight but have reduced fat mass compared with wild type (WT) mice [16,17], and normal levels of glucose and insulin [6]. Under high fat diet Gipr-/- mice, in comparison to WT mice, have a reduced fat storage; they use fat as the main energy substrate and do not develop obesity, insulin resistance, diabetes mellitus, impaired glucose tolerance, and fatty liver like the WT [6,7,15-18]. Additionally, GIP signaling is required for effective accumulation of nutrients under high-fat diet, and inhibition of GIP signaling not only prevents obesity but also insulin resistance [19]. Recently, a study in mice [20] showed that vaccination against GIP prevents its binding to the GIP receptor, consequently reducing body weight gain under high fat diets. Nitz et al. [21] showed preliminary evidence for nominal association of a non-synonymous GIPR polymorphism (rs1800437) and cardiovascular disease (CVD).
