INS and obesity due to melanocortin 4 receptor deficiency: The finding that transgenic mice with primary deficiency of BAT or lack of UCP-1 were prone to develop obesity, together with the evidence that BAT activation was associated with improved insulin-sensitivity both in humans and in animal models, has led to the hypothesis that stimulating BAT activity might be a promising strategy in preventing fat mass accumulation and insulin-resistance in obesity [32,78,79].