Abstract | BACKGROUND: METHODS: We investigated the metabolic effects of C12TPP in isolated brown-fat mitochondria, brown adipocyte cultures and mice in vivo. Experimental approaches included the measurement of oxygen consumption, carbon dioxide production, western blotting, magnetic resonance imaging and bomb calorimetry. RESULTS: In mice, C12TPP (50 μmol per (day•kg body weight)) in the drinking water significantly reduced body weight (12%, P<0.001) and body fat mass (24%, P<0.001) during the first 7 days of treatment. C12TPP did not affect water palatability and intake or the energy and lipid content in feces. The addition of C12TPP to isolated brown-fat mitochondria resulted in increased oxygen consumption. Three hours of pretreatment with C12TPP also increased oligomycin-insensitive oxygen consumption in brown adipocyte cultures (P<0.01). The effects of C12TPP on mitochondria, cells and mice were independent of uncoupling protein 1 (UCP1). However, C12TPP treatment increased the mitochondrial protein levels in the brown adipose tissue of both wild-type and UCP1-knockout mice. Pair-feeding revealed that one-third of the body weight loss in C12TPP-treated mice was due to reduced food intake. C12TPP treatment elevated the resting metabolic rate (RMR) by up to 18% (P<0.05) compared with pair-fed animals. C12TPP reduced the respiratory exchange ratio, indicating enhanced fatty acid oxidation in mice. CONCLUSIONS: C12TPP combats diet-induced obesity by reducing food intake, increasing the RMR and enhancing fatty acid oxidation.
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Authors | A V Kalinovich, C L Mattsson, M R Youssef, N Petrovic, M Ost, V P Skulachev, I G Shabalina |
Journal | International journal of obesity (2005)
(Int J Obes (Lond))
Vol. 40
Issue 12
Pg. 1864-1874
(12 2016)
ISSN: 1476-5497 [Electronic] England |
PMID | 27534841
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Mitochondrial Proteins
- Organophosphorus Compounds
- Ucp1 protein, mouse
- Uncoupling Protein 1
- dodecyltriphenylphosphonium
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Topics |
- Adipocytes, Brown
(metabolism)
- Adipose Tissue, Brown
(metabolism)
- Animals
- Diet, High-Fat
(adverse effects)
- Disease Models, Animal
- Energy Metabolism
- Lipid Metabolism
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Mitochondria
(drug effects, metabolism)
- Mitochondrial Proteins
(metabolism)
- Obesity
(drug therapy, etiology, metabolism, pathology)
- Organophosphorus Compounds
(metabolism, pharmacokinetics, pharmacology)
- Thermogenesis
(drug effects, physiology)
- Uncoupling Protein 1
(metabolism)
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