LEP and obesity due to melanocortin 4 receptor deficiency: Several hypothetical explanations have been proposed for this inverse association between obesity and risk of mortality, including clinicians’ lower threshold for ICU admission of obese patients, confounding, reverse causality, secretion of immunomodulatory substances by adipocytes (e.g., leptin, interleukin-10, and soluble TNF-α receptor) that may attenuate the inflammatory response, and the increased metabolic reserve provided by excess fat stores and lean body mass in obese patients that may counteract the increased catabolic stress and improve survival during critical illness (46).