LEP and obesity due to melanocortin 4 receptor deficiency: In the livers of both genetic (ob/ob; leptin deficient) and HFD-induced mouse models for obesity, mitochondria–ER contact was greater than in lean controls, resulting in increased Ca2+ flux from the ER to mitochondria, mitochondrial Ca2+ overload, compromised mitochondrial oxidative capacity, and augmented oxidative stress [98].