Abstract
MnTBAP ameliorates dietâinduced insulin resistance by reducing adiposity and increasing AKT expression in skeletal muscle (854.7)
The FASEB journal, Vol.28(S1), p.854.7
04/2014
DOI: 10.1096/fasebj.28.1_supplement.854.7
Abstract
Abstract only
Manganese tetrakis benzoic acid porphyrin (MnTBAP) is a superoxide dismutase mimetic that decreases adiposity but does not improve insulin action in dietâinduced obese mice (Pires et al., 2013). In leptin deficient Ob/Ob mice, MnTBAP improves insulin sensitivity without reducing adiposity (Houstis et al., 2006). The present study investigated whether MnTBAP treatment improves leptin sensitivity and insulin action in dietâinduced obese mice. Mice were fed a high fat diet (HFD) or a low fat diet (LFD) for six months. During the last five weeks of the dietary intervention, HFD and LFD mice were treated with MnTBAP or vehicle. After one week of MnTBAP treatment, a time point at which caloric intake is reduced but no significant weight loss has occurred, leptin sensitivity was assessed by injecting mice with leptin and monitoring food intake. Although mice fed a HFD were leptin resistant, MnTBAP did not alter the ability of leptin to reduce food intake. After four weeks of MnTBAP treatment, a time point when significant weight loss has occurred in HFD mice, insulin sensitivity was assessed by an insulinâassisted glucose tolerance test (IAGTT). Blood glucose values during the IAGT T were lower in HFD mice treated with MnTBAP compared to vehicle. MnTBAP treatment did not alter blood glucose values during the IAGT in LFD mice. Skeletal muscle from HFD mice treated with MnTBAP exhibited a significant increase in insulinâstimulated phosphorylation of AKT. The increase in AKT phosphorylation in muscle was due to a significant increase in AKT1 and AKT2 protein expression, without significant changes in AKT1 and AKT2 mRNA levels, suggesting a postâtranscriptional mechanism. Taken together, our results indicate that MnTBAP improves insulin sensitivity by reducing adiposity and augmenting insulin signaling associated with increased AKT expression. The antiâobesity action of MnTBAP is related to a reduction in caloric intake, a process that appears to be independent of changes in leptin sensitivity.
Grant Funding Source
: Supported by NIH 1 R15 DK090722â01
Details
- Title: Subtitle
- MnTBAP ameliorates dietâinduced insulin resistance by reducing adiposity and increasing AKT expression in skeletal muscle (854.7)
- Creators
- Timothy Brodsky - Skidmore CollegeJonathan Brestoff - Skidmore CollegeAlexandra Sosinsky - Skidmore CollegeRyan McLoughlin - Skidmore CollegeLingzhi Cai - University of PittsburghErin Kershaw - University of PittsburghThomas Reynolds - Skidmore College
- Resource Type
- Abstract
- Publication Details
- The FASEB journal, Vol.28(S1), p.854.7
- DOI
- 10.1096/fasebj.28.1_supplement.854.7
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Language
- English
- Date published
- 04/2014
- Academic Unit
- Orthopedics and Rehabilitation
- Record Identifier
- 9984700457102771
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