Lorcaserin and adiposopathy: 5-HT2c agonism as a treatment for 'sick fat' and metabolic disease.
Agonists of 5-hydroxytryptamine (5-HT; serotonin) receptors promote loss of excessive body fat (adiposity) and improve metabolic parameters associated with adiposity-induced adipose tissue dysfunction (adiposopathy or 'sick fat'). By improving adipose tissue pathogenic endocrine and immune responses in overweight patients, 5-HT receptor agonists may improve metabolic disease. Lorcaserin (APD-356) is a selective 5-HT2c receptor agonist that promotes weight loss. Probably owing to its selectivity for the 5-HT2c receptor, clinical trial evidence supports that lorcaserin does not adversely affect heart valves or pulmonary artery pressure. This review examines: the mechanisms by which serotonergic pathways improve adiposity and adiposopathy; historical data and perspective regarding the efficacy and safety of prior 5-HT agonists; speculation regarding future paradigms in treating adiposopathy; and why lorcaserin may prove to be a safe and generally well-tolerated agent that not only improves the weight of patients, but also improves the health of patients.
Bays
Harold E
HE
Louisville Metabolic and Atherosclerosis Research Center, 3288 Illinois Avenue, Louisville KY 40213, USA. hbaysmd@aol.com
D050154:Adiposity / Q000187:drug effects / Q000502:physiology; D019440:Anti-Obesity Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001552:Benzazepines / Q000009:adverse effects / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D006801:Humans; D008659:Metabolic Diseases / Q000188:drug therapy* / Q000503:physiopathology; D009765:Obesity / Q000188:drug therapy*; D058826:Serotonin 5-HT2 Receptor Agonists
D019440:Anti-Obesity Agents; D001552:Benzazepines; D058826:Serotonin 5-HT2 Receptor Agonists; C506658:lorcaserin