title: Manganese [III] Tetrakis [5,10,15,20]-Benzoic Acid Porphyrin Reduces Adiposity and Improves Insulin Action in Mice with Pre-Existing Obesity.
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.
authors.affiliation: Department of Health and Exercise Sciences, Skidmore College, Saratoga Springs, New York, United States of America.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Brestoff
authors.affiliation: Department of Health and Exercise Sciences, Skidmore College, Saratoga Springs, New York, United States of America.
authors.forename: Tim
authors.initials: T
authors.lastname: Brodsky
authors.affiliation: Department of Health and Exercise Sciences, Skidmore College, Saratoga Springs, New York, United States of America.
authors.forename: Alexandra Z
authors.initials: AZ
authors.lastname: Sosinsky
authors.affiliation: Department of Health and Exercise Sciences, Skidmore College, Saratoga Springs, New York, United States of America.
authors.forename: Ryan
authors.initials: R
authors.lastname: McLoughlin
authors.affiliation: Department of Health and Exercise Sciences, Skidmore College, Saratoga Springs, New York, United States of America.
authors.forename: Elena
authors.initials: E
authors.lastname: Stansky
authors.affiliation: Department of Health and Exercise Sciences, Skidmore College, Saratoga Springs, New York, United States of America.
authors.forename: Leila
authors.initials: L
authors.lastname: Fussell
authors.affiliation: Department of Health and Exercise Sciences, Skidmore College, Saratoga Springs, New York, United States of America.
authors.forename: Aaron
authors.initials: A
authors.lastname: Sheppard
authors.affiliation: Department of Health and Exercise Sciences, Skidmore College, Saratoga Springs, New York, United States of America.
authors.forename: Maria
authors.initials: M
authors.lastname: DiSanto-Rose
authors.affiliation: Division of Endocrinology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Erin E
authors.initials: EE
authors.lastname: Kershaw
authors.affiliation: Department of Health and Exercise Sciences, Skidmore College, Saratoga Springs, New York, United States of America.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Reynolds
mesh_terms: D050154:Adiposity / Q000187:drug effects*; D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001786:Blood Glucose; D059305:Diet, High-Fat / Q000009:adverse effects; D004353:Drug Evaluation, Preclinical; D002149:Energy Intake / Q000187:drug effects; D004734:Energy Metabolism; D006706:Homeostasis; D007328:Insulin / Q000502:physiology*; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology* / Q000627:therapeutic use; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
chemical_list: D019440:Anti-Obesity Agents; D001786:Blood Glucose; D007328:Insulin; D008665:Metalloporphyrins; C097284:manganese(III)-tetrakis(4-benzoic acid)porphyrin; D051057:Proto-Oncogene Proteins c-akt