Antagonizing the Leptin Receptor in Obesity

This editorial discusses the challenges of treating childhood obesity, particularly cases involving leptin resistance. It highlights a study by Funcke et al. (2023) that identified rare antagonistic leptin variants in two severely overweight children, leading to resistance to conventional metreleptin therapy. The authors demonstrated that high doses of metreleptin, combined with fasting and exercise, overcame the antagonistic effects of variant leptin, resulting in significant weight loss. The findings suggest that endogenous variant hormones can competitively antagonize their nonvariant counterparts, offering insights into potential therapeutic strategies for leptin-resistant obesity. The editorial also explores broader implications for understanding leptin signaling and its role in metabolic regulation.

This editorial discusses the challenges of treating childhood obesity, particularly cases involving leptin resistance. It highlights a study by Funcke et al. (2023) that identified rare antagonistic leptin variants in two severely overweight children, leading to resistance to conventional metreleptin therapy. The authors demonstrated that high doses of metreleptin, combined with fasting and exercise, overcame the antagonistic effects of variant leptin, resulting in significant weight loss. The findings suggest that endogenous variant hormones can competitively antagonize their nonvariant counterparts, offering insights into potential therapeutic strategies for leptin-resistant obesity. The editorial also explores broader implications for understanding leptin signaling and its role in metabolic regulation.