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New players in high fat diet-induced obesity: LETM1 and CTMP.

AbstractOBJECTIVE:
Obesity contributes to insulin resistance and is a risk factor for diabetes. C-terminal modulator protein (CTMP) and leucine zipper/EF-hand-containing transmembrane protein 1 (LETM1) have been reported to influence the phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB) signaling pathway via the modulation of PKB activity, a key player for insulin signaling. However, it remains unclear whether CTMP and LETM1 are associated with PI3K/PKB signaling in mouse models of obesity.
MATERIALS/METHODS:
To address this question, we used two different mouse models of obesity, including high-fat diet (HFD)-induced diabetic mice and genetically modified obese mice (ob/ob mice). The levels of insulin-signaling molecules in these mice were determined by immunohistochemical and Western blot analyses. The involvement of CTMP and LETM1 in PI3K/PKB signaling was investigated in HEK293 cells by transient transfection and adenovirus-mediated infection.
RESULTS:
We found that the levels of insulin receptor, phosphorylated PKB, and LETM1 were lower and the level of CTMP was higher in the adipose tissue of obese mice on an HFD compared to lean mice on a chow diet. Similar results were obtained in ob/ob mice. In HEK293 cells, the activation of PKB increased the LETM1 level, and inhibition of PKB increased the CTMP level. The overexpression of CTMP suppressed the insulin-induced increase in PKB phosphorylation, which was abrogated by co-overexpression with LETM1.
CONCLUSION:
These results suggest that CTMP and LETM1 may participate in impaired insulin signaling in the adipose tissue of obese mice, raising the possibility that these parameters may serve as new candidate biomarkers or targets in the development of new therapeutic approaches for diabetes.
AuthorsJisoo Park, Yuwen Li, Seon-Hwan Kim, Keum-Jin Yang, Gyeyeong Kong, Robin Shrestha, Quangdon Tran, Kyeong Ah Park, Juhee Jeon, Gang Min Hur, Chul-Ho Lee, Dong-Hoon Kim, Jongsun Park
JournalMetabolism: clinical and experimental (Metabolism) Vol. 63 Issue 3 Pg. 318-27 (Mar 2014) ISSN: 1532-8600 [Electronic] United States
PMID24333006 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 Elsevier Inc. All rights reserved.
Chemical References
  • Adaptor Proteins, Signal Transducing
  • CTMP protein, mouse
  • Calcium-Binding Proteins
  • Carrier Proteins
  • Insulin
  • LETM1 protein, human
  • Membrane Proteins
  • Phosphatidylinositol 3-Kinases
  • Receptor, Insulin
  • Proto-Oncogene Proteins c-akt
  • THEM4 protein, human
  • Thiolester Hydrolases
Topics
  • Adaptor Proteins, Signal Transducing (genetics, metabolism)
  • Adipose Tissue (metabolism)
  • Adiposity (genetics)
  • Animals
  • Calcium-Binding Proteins (genetics, metabolism)
  • Carrier Proteins (metabolism)
  • Cell Line
  • Diet, High-Fat (methods)
  • Down-Regulation (genetics)
  • HEK293 Cells
  • Humans
  • Insulin (genetics, metabolism)
  • Male
  • Membrane Proteins (genetics, metabolism)
  • Mice
  • Mice, Inbred C57BL
  • Mice, Obese
  • Obesity (genetics, metabolism)
  • Phosphatidylinositol 3-Kinases (genetics, metabolism)
  • Proto-Oncogene Proteins c-akt (genetics, metabolism)
  • Receptor, Insulin (genetics, metabolism)
  • Signal Transduction (genetics)
  • Thiolester Hydrolases (genetics, metabolism)

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