PloS one, 2015-09, Vol.10 (9), p.e0137388-e0137388
2015
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- Autor(en) / Beteiligte
- Titel
- Manganese [III] Tetrakis [5,10,15,20]-Benzoic Acid Porphyrin Reduces Adiposity and Improves Insulin Action in Mice with Pre-Existing Obesity
- Ist Teil von
- PloS one, 2015-09, Vol.10 (9), p.e0137388-e0137388
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2015
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- The superoxide dismutase mimetic manganese [III] tetrakis [5,10,15,20]-benzoic acid porphyrin (MnTBAP) is a potent antioxidant compound that has been shown to limit weight gain during short-term high fat feeding without preventing insulin resistance. However, whether MnTBAP has therapeutic potential to treat pre-existing obesity and insulin resistance remains unknown. To investigate this, mice were treated with MnTBAP or vehicle during the last five weeks of a 24-week high fat diet (HFD) regimen. MnTBAP treatment significantly decreased body weight and reduced white adipose tissue (WAT) mass in mice fed a HFD and a low fat diet (LFD). The reduction in adiposity was associated with decreased caloric intake without significantly altering energy expenditure, indicating that MnTBAP decreases adiposity in part by modulating energy balance. MnTBAP treatment also improved insulin action in HFD-fed mice, a physiologic response that was associated with increased protein kinase B (PKB) phosphorylation and expression in muscle and WAT. Since MnTBAP is a metalloporphyrin molecule, we hypothesized that its ability to promote weight loss and improve insulin sensitivity was regulated by heme oxygenase-1 (HO-1), in a similar fashion as cobalt protoporphyrins. Despite MnTBAP treatment increasing HO-1 expression, administration of the potent HO-1 inhibitor tin mesoporphyrin (SnMP) did not block the ability of MnTBAP to alter caloric intake, adiposity, or insulin action, suggesting that MnTBAP influences these metabolic processes independent of HO-1. These data demonstrate that MnTBAP can ameliorate pre-existing obesity and improve insulin action by reducing caloric intake and increasing PKB phosphorylation and expression.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0137388Titel-ID: cdi_plos_journals_1719304164
- Format
- –
- Schlagworte
- Acids, Adipose tissue, Adiposity - drug effects, AKT protein, Animal tissues, Animals, Anti-Obesity Agents - pharmacology, Anti-Obesity Agents - therapeutic use, Antioxidants, Benzoic acid, Blood Glucose, Body weight, Body weight gain, Body weight loss, Cobalt, Diet, Diet, High-Fat - adverse effects, Drug Evaluation, Preclinical, Energy balance, Energy expenditure, Energy Intake - drug effects, Energy Metabolism, Fuel consumption, Glucose, Heme, Heme oxygenase (decyclizing), High fat diet, Homeostasis, Hypocaloric diet, Insulin, Insulin - physiology, Insulin resistance, Kinases, Low fat, Low fat diet, Male, Manganese, Manganese (Metal), Metalloporphyrins - pharmacology, Metalloporphyrins - therapeutic use, Mice, Mice, Inbred C57BL, Muscles, Nutrient deficiency, Obesity, Obesity - drug therapy, Obesity - etiology, Obesity - metabolism, Oxygenase, Phosphorylation, Physiological aspects, Prevention, Protein Processing, Post-Translational, Proto-Oncogene Proteins c-akt - metabolism, Rodents, Superoxide dismutase, Tin, Weight reduction