Leptin has central importance in the global obesity and cardiovascular disease problem. Leptin is principally secreted by adipocytes and acts in the hypothalamus to suppress appetite and food intake, increase energy expenditure, and regulate body weight. Based on clinical translation of specific and networked actions, leptin affects the cardiovascular system and may be a marker and driver of cardiometabolic risk factors with interventions that are actionable by cardiologists. Leptin subnetwork analysis demonstrates a statistically significant role for ethnoculturally and socioeconomically appropriate lifestyle intervention in cardiovascular disease. Emergent mechanistic components and potential diagnostic or therapeutic targets include hexokinase 3, urocortins, clusterin, sialic acid-binding immunoglobulin-like lectin 6, C-reactive protein, platelet glycoprotein VI, albumin, pentraxin 3, ghrelin, obestatin prepropeptide, leptin receptor, neuropeptide Y, and corticotropin-releasing factor receptor 1. Emergent associated symptoms include weight change, eating disorders, vascular necrosis, chronic fatigue, and chest pain. Leptin-targeted therapies are reported for lipodystrophy and leptin deficiency, but they are investigational for leptin resistance, obesity, and other chronic diseases.

Highlights

• Leptin is an adipokine with central importance in the global obesity problem and consequent cardiovascular disease and is principally secreted by adipocytes and acts in the hypothalamus to suppress appetite and food intake, increase energy expenditure, and regulate body weight.
• Network analysis of leptin physiology is a valuable hypothesis-generating research tool. Leptin subnetwork analysis demonstrates a statistically significant role for lifestyle intervention in cardiovascular disease. Emergent mechanistic components that have potential as diagnostic or therapeutic markers include hexokinase 3, urocortins, clusterin, sialic acid-binding immunoglobulin-like lectin C6, C-reactive protein, platelet glycoprotein VI, albumin, pentraxin 3, ghrelin, obestatin prepropeptide, LepR, NPY, and corticotropin-releasing factor receptor 1. Emergent symptoms associated with leptin physiology include weight change, eating disorders, vascular necrosis, chronic fatigue, and chest pain. Clinical translation of these findings can enhance clinical decision making by cardiologists in the management of obesity and cardiometabolic risk mitigation.
• Leptin-targeted therapies are reported for lipodystrophy and leptin deficiency but are still investigational for leptin resistance, obesity, and other chronic diseases.