Figure 5.

Adropin-deficiency does not affect weight gain associated with high-fat diets, but is associated with an increased severity of impaired glucose homeostasis associated with obesity. (a) Body composition of wild-type control (WT), heterozygous carriers of the null adropin allele (HET) and adropin knockout (KO) mice weaned onto chow, and then after 8 weeks on the high-fat diet (60% kJ/fat, HFD) (n = 6/group). Exposure to the HFD resulted in weight gain predominantly due to increased fat mass. Body weight and composition were not significantly different after 8 weeks on HFD; at the start of the study, there was a tendency (P = 0.07) for increased fat mass in adropin knockout mice. (b) Food intake expressed as kJ/day was not significantly affected by genotype. Food intake was recorded over a 1 month period. (c–e) Insulin and glucose measurements recorded at the end of 8 weeks on HFD. Hyperinsulinemia and hyperglycemia were more severe in adropin knockout mice relative to WT. The differences in insulin, blood glucose and homeostasis model assessment–insulin resistance (HOMA_IR) between WT and KO were significant (*P < 0.05, **P < 0.001). The differences in insulin, blood glucose, and HOMA_IR between HET and KO were not statistically significant. (e) Adropin knockout mice exhibited fasting hypertriglyceridemia (*P < 0.05 vs. WT). (f, g) Impaired glucose tolerance associated with diet-induced obesity is more severe in heterozygous and homozygous carriers of the null adropin allele. Shown are the raw data (f, P < 0.05 when comparing WT vs. *KO only, **WT vs. KO and HET, ^#WT vs. HET only) and the area under the curve (AUC) above baseline levels (g, *P < 0.05 vs. WT). (h, i) Insulin tolerance tests suggest reduced insulin action in AdrKO carriers of the null adropin allele fed high-fat diet. *P < 0.05, WT vs. KO.