Lysine-Specific Demethylase 1 in Energy Metabolism: A Novel Target for Obesity

Obesity develops from an imbalance of energy homeostasis and is associated with the development of metabolic disorders, including insulin resistance and type 2 diabetes. Identification of the underlying molecular mechanisms and effective therapeutic approaches is highly needed. Lysine-specific demethylase 1 (LSD1), an flavin adenine dinucletide-dependent amine oxidase, is implicated in a wide variety of biological processes, including tumorigenesis, stem cell fate decisions, and embryonic development. Recent studies have suggested a vital role of LSD1 in regulating adaptive thermogenesis, mitochondrial biogenesis, glucose, and lipid metabolism. More recently, LSD1 activity was found to be regulated by nutrients, energy status, and hormonal signals, suggesting that it may act as a novel sensor for nutritional regulation of metabolic health. Here, we first discuss the effects of LSD1 on physiological phenotypes, including body weight, fat mass, body temperature, and glucose homeostasis. We also summarize recent understanding of the physiological roles and underlying mechanisms of LSD1 in controlling metabolic functions of adipose and other tissues. Hopefully, a better understanding of the roles of LSD1 in metabolic regulation may provide new perspectives for the nutritional prevention and treatment of obesity.