title: Nifedipine increases energy expenditure by increasing PGC-1α expression in skeletal muscle.
abstract: Nifedipine, an L-type calcium (Ca) channel blocker, is one of the most widely used Ca channel-blocking medications for hypertension. Previous studies have reported an association of nifedipine hypertensive treatment with decreased body weight in obese hypertensive humans and rat models. However, the precise mechanism underlying how nifedipine functions metabolically has not been elucidated. Here, we investigated the long-term effect of a non-hypotensive nifedipine dose using a mildly obese, endothelial NO synthase-deficient mouse model. Treating these mice with nifedipine decreased their body weight gain ratio, and white adipose tissue weight compared with the untreated controls. Metabolic analyses indicated that nifedipine treatment upregulated whole-body energy expenditure through increasing oxygen consumption and reducing the respiratory exchange ratio, suggesting that nifedipine promotes lipid oxidation rather than carbohydrate utilization. Furthermore, nifedipine treatment upregulated the expression of the peroxisome proliferator-activated receptor-γ coactivator -1α (PGC-1α) in skeletal muscle. Overall, these results suggest that a non-hypotensive dose of nifedipine has pleiotropic effects on energy expenditure that could ameliorate obesity.
authors.affiliation: Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, Japan.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Tian
authors.forename: Keishi
authors.initials: K
authors.lastname: Miyata
authors.forename: Mitsuhisa
authors.initials: M
authors.lastname: Tabata
authors.forename: Masato
authors.initials: M
authors.lastname: Yano
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Tazume
authors.forename: Jun
authors.initials: J
authors.lastname: Aoi
authors.forename: Otowa
authors.initials: O
authors.lastname: Takahashi
authors.forename: Kimi
authors.initials: K
authors.lastname: Araki
authors.forename: Michio
authors.initials: M
authors.lastname: Kawasuji
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Oike
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects* / Q000502:physiology; D050356:Lipid Metabolism / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology*; D052250:Nitric Oxide Synthase Type III / Q000172:deficiency / Q000235:genetics; D009765:Obesity / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors; D015430:Weight Gain / Q000187:drug effects / Q000502:physiology
chemical_list: D002121:Calcium Channel Blockers; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D052250:Nitric Oxide Synthase Type III; D009543:Nifedipine