New players in high fat diet-induced obesity

Letm1 and Ctmp

Jisoo 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-Hun Kim, Jongsun Park

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Objective 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.

Original languageEnglish
Pages (from-to)318-327
Number of pages10
JournalMetabolism: Clinical and Experimental
Volume63
Issue number3
DOIs
Publication statusPublished - 2014 Mar 1

Fingerprint

Proto-Oncogene Proteins c-akt
High Fat Diet
Obesity
Obese Mice
1-Phosphatidylinositol 4-Kinase
Proteins
Insulin
HEK293 Cells
Adipose Tissue
EF Hand Motifs
Adenoviridae Infections
Leucine Zippers
Insulin Receptor
Transfection
Insulin Resistance
Biomarkers
Western Blotting
Phosphorylation
Diet

Keywords

  • CTMP
  • Insulin signaling
  • LETM1
  • Obesity
  • PKB

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Park, J., Li, Y., Kim, S. H., Yang, K. J., Kong, G., Shrestha, R., ... Park, J. (2014). New players in high fat diet-induced obesity: Letm1 and Ctmp. Metabolism: Clinical and Experimental, 63(3), 318-327. https://doi.org/10.1016/j.metabol.2013.10.012

New players in high fat diet-induced obesity : Letm1 and Ctmp. / Park, Jisoo; Li, Yuwen; Kim, Seon Hwan; Yang, Keum Jin; Kong, Gyeyeong; Shrestha, Robin; Tran, Quangdon; Park, Kyeong Ah; Jeon, Juhee; Hur, Gang Min; Lee, Chul Ho; Kim, Dong-Hun; Park, Jongsun.

In: Metabolism: Clinical and Experimental, Vol. 63, No. 3, 01.03.2014, p. 318-327.

Research output: Contribution to journalArticle

Park, J, Li, Y, Kim, SH, Yang, KJ, Kong, G, Shrestha, R, Tran, Q, Park, KA, Jeon, J, Hur, GM, Lee, CH, Kim, D-H & Park, J 2014, 'New players in high fat diet-induced obesity: Letm1 and Ctmp', Metabolism: Clinical and Experimental, vol. 63, no. 3, pp. 318-327. https://doi.org/10.1016/j.metabol.2013.10.012
Park, Jisoo ; Li, Yuwen ; Kim, Seon Hwan ; Yang, Keum Jin ; Kong, Gyeyeong ; Shrestha, Robin ; Tran, Quangdon ; Park, Kyeong Ah ; Jeon, Juhee ; Hur, Gang Min ; Lee, Chul Ho ; Kim, Dong-Hun ; Park, Jongsun. / New players in high fat diet-induced obesity : Letm1 and Ctmp. In: Metabolism: Clinical and Experimental. 2014 ; Vol. 63, No. 3. pp. 318-327.
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AU - Kong, Gyeyeong

AU - Shrestha, Robin

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AU - Hur, Gang Min

AU - Lee, Chul Ho

AU - Kim, Dong-Hun

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N2 - Objective 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.

AB - Objective 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.

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