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Manganese [III] tetrakis [5,10,15,20]-benzoic acid porphyrin reduces adiposity and improves insulin action in mice with pre-existing obesity

Brestoff, JR and Brodsky, T and Sosinsky, AZ and McLoughlin, R and Stansky, E and Fussell, L and Sheppard, A and DiSanto-Rose, M and Kershaw, EE and Reynolds, TH (2015) Manganese [III] tetrakis [5,10,15,20]-benzoic acid porphyrin reduces adiposity and improves insulin action in mice with pre-existing obesity. PLoS ONE, 10 (9).

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Abstract

© 2015 Brestoff et al. 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.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Brestoff, JR
Brodsky, T
Sosinsky, AZ
McLoughlin, R
Stansky, E
Fussell, L
Sheppard, A
DiSanto-Rose, M
Kershaw, EEkershawe@pitt.eduKERSHAWE
Reynolds, TH
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorAndrews, ZaneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 23 September 2015
Date Type: Publication
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Journal or Publication Title: PLoS ONE
Volume: 10
Number: 9
DOI or Unique Handle: 10.1371/journal.pone.0137388
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Medicine
Refereed: Yes
Date Deposited: 23 Aug 2016 14:39
Last Modified: 26 Jan 2019 10:55
URI: http://d-scholarship.pitt.edu/id/eprint/28382

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