Mice with IP6K1 deletion [423,429,430] or pharmacological IP6K inhibition [431–433] show improved insulin sensitivity and are resistant to diet-induced obesity, which has been attributed to AMPK activation and thermogenic energy expenditure in adipose tissue [429–431], and potentially to enhanced adipose tissue lipolysis [434]. Here, IP6K1 is linked to obesity due to melanocortin 4 receptor deficiency.