In work published in the Journal of Clinical Endocrinology & Metabolism, Prof Sadaf Farooqi and her team used metabolomic profiling to understand leptin’s effects on peripheral metabolism. Rare patients with congenital leptin deficiency have hyperphagia and severe early onset obesity, which is treatable with injections of recombinant leptin. Comparison of metabolome profiles in patients before and after acute treatment with leptin (prior to weight loss) demonstrated class-wide shifts in multiple metabolite groups. Some but not all of these changes were also seen following acute caloric restriction in healthy volunteers, indicating that leptin has effects on peripheral metabolism independent of caloric intake. Additionally, by analysing the metabolomes of patients with other rare genetic causes of severe obesity, the team validated the use of a previously reported metabolomic signature associated with obesity, in patients at the upper extremes of the body mass index (BMI) spectrum.