title: The antidepressant trans-2-phenylcyclopropylamine protects mice from high-fat-diet-induced obesity.
abstract: Mice treated with the antidepressant trans-2-phenylcyclopropylamine (2-PCPA) were protected against diet-induced-obesity, and adiposity was reversed in pre-established diet-induced obese mice. Contrary to a recent report that inhibition of lysine-specific demethylase-1 by 2-PCPA results in increased energy expenditure, long-term 2-PCPA treatment had no such effect but its protection against obesity was associated with increased spontaneous locomotor activity, Moreover, pair feeding to assure equal caloric intake in wild type mice as well as in genetic hyperphagic mice (ob/ob) also resulted in weight reduction in 2-PCPA treated mice that correlated with increased activity but no change in energy expenditure. Similarly, short-term intraperitoneal injections of 2-PCPA did not affect food intake but caused a substantial increase in locomotor activity in the light cycle that correlated with increased energy expenditure, whereas activity and energy expenditure were unchanged in the dark cycle. Lastly, 2-PCPA was also effective in reducing obesity in genetic UCP1 null mice. These data suggest that 2-PCPA can reduce obesity by decreasing food intake in the long term while increasing activity in the short-term. However, the protective and weight loss effects of 2-PCPA are independent of UCP1-regulated thermogenesis or basal energy expenditure.
authors.affiliation: Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors.forename: Adi
authors.initials: A
authors.lastname: Shemesh
authors.affiliation: Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors.forename: Arian
authors.initials: A
authors.lastname: Abdulla
authors.affiliation: Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York, United States of America ; Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors.forename: Fajun
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors.forename: Streamson C
authors.initials: SC
authors.lastname: Chua
authors.affiliation: Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York, United States of America ; Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Pessin
authors.affiliation: Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York, United States of America ; Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors.forename: Haihong
authors.initials: H
authors.lastname: Zong
mesh_terms: D000818:Animals; D001823:Body Composition / Q000187:drug effects; D059305:Diet, High-Fat / Q000009:adverse effects*; D004435:Eating / Q000187:drug effects*; D002149:Energy Intake / Q000187:drug effects; D005951:Glucose Tolerance Test; D008297:Male; D051379:Mice; D008820:Mice, Obese; D009765:Obesity / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control*; D014191:Tranylcypromine / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D014191:Tranylcypromine