Journal article
Manganese [III] Tetrakis [5,10,15,20]-Benzoic Acid Porphyrin Reduces Adiposity and Improves Insulin Action in Mice with Pre-Existing Obesity
PloS one, Vol.10(9), pp.e0137388-e0137388
09/23/2015
DOI: 10.1371/journal.pone.0137388
PMCID: PMC4580604
PMID: 26397111
Abstract
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.
Details
- Title: Subtitle
- Manganese [III] Tetrakis [5,10,15,20]-Benzoic Acid Porphyrin Reduces Adiposity and Improves Insulin Action in Mice with Pre-Existing Obesity
- Creators
- Jonathan R. Brestoff - Skidmore CollegeTim Brodsky - Skidmore CollegeAlexandra Z. Sosinsky - Skidmore CollegeRyan McLoughlin - Skidmore CollegeElena Stansky - Skidmore CollegeLeila Fussell - Skidmore CollegeAaron Sheppard - Skidmore CollegeMaria DiSanto-Rose - Skidmore Coll, Dept Hlth & Exercise Sci, Saratoga Springs, NY 12866 USAErin E. Kershaw - University of PittsburghThomas H. Reynolds - Skidmore College
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.10(9), pp.e0137388-e0137388
- Publisher
- Public Library Science
- DOI
- 10.1371/journal.pone.0137388
- PMID
- 26397111
- PMCID
- PMC4580604
- ISSN
- 1932-6203
- eISSN
- 1932-6203
- Number of pages
- 17
- Grant note
- R15DK090722 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) 1 R15 DK090722-01 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 09/23/2015
- Academic Unit
- Orthopedics and Rehabilitation
- Record Identifier
- 9984697640302771
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