title: Cyclophilin D deficiency prevents diet-induced obesity in mice.
abstract: Mitochondrial coupling efficiency is pivotal in thermogenesis and energy homeostasis. Here we show that deletion of cyclophilin D (CypD), a key modulator of the mitochondrial permeability transition pore, demonstrated resistance to diet-induced obesity (DIO) in both male and female mice, due to increased basal metabolic rate, heat production, total energy expenditure and expenditure of fat energy, despite increased food consumption. Absorption of fatty acids is not altered between CypD(-/-) and wild-type mice. Adult CypD(-/-) developed hyperglycemia, insulin resistance and glucose intolerance albeit resistant to DIO. These data demonstrate that inhibition of CypD function could protect from HFD-IO by increasing energy expenditure in both male and female mice. Inhibition of CypD may offer a novel target to modulate metabolism.
authors.affiliation: Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE 68198-5850, USA.
authors.forename: Kishor
authors.initials: K
authors.lastname: Devalaraja-Narashimha
authors.forename: Alicia M
authors.initials: AM
authors.lastname: Diener
authors.forename: Babu J
authors.initials: BJ
authors.lastname: Padanilam
mesh_terms: D000818:Animals; D001481:Basal Metabolism; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins / Q000235:genetics / Q000378:metabolism*; D004041:Dietary Fats / Q000009:adverse effects*; D002149:Energy Intake; D004734:Energy Metabolism; D005260:Female; D018149:Glucose Intolerance / Q000209:etiology; D006943:Hyperglycemia / Q000209:etiology; D007333:Insulin Resistance; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D009765:Obesity / Q000188:drug therapy / Q000235:genetics*; D012727:Sex Characteristics; D022722:Thermogenesis
chemical_list: D000081406:Peptidyl-Prolyl Isomerase F; D004041:Dietary Fats; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D024101:Mitochondrial Proteins; C000631446:PPIF protein, mouse; D021983:Cyclophilins