Fascinatingly, wild-type mice exposed to a high-fat diet exhibit increased plasma osteopontin levels with elevated expression in macrophages recruited into adipose tissue, while on the other hand, obese osteopontin null mice exhibit decreased markers of inflammation with less macrophage infiltration into adipose tissue, display improved insulin sensitivity, and are seemingly protected from the effects of diet-induced obesity on body composition or energy expenditure [100]. The gene discussed is SPP1; the disease is obesity due to melanocortin 4 receptor deficiency.