INS and obesity due to melanocortin 4 receptor deficiency: In high-fat fed Ldlr−/− mice, addition of nobiletin (0.1% and 0.3% w/w) resulted in a dramatic reduction in both hepatic and intestinal TG accumulation, attenuation of VLDL-TG secretion, normalization of insulin sensitivity and conferred an almost complete resistance to obesity, without effect on caloric consumption or fat absorption [48].