title: New players in high fat diet-induced obesity: LETM1 and CTMP.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Metabolic Disease Institute, University of Cincinnati, Cincinnati, OH 45437, USA; Department of Pharmacology, Metabolic Diseases and Cell Signaling Laboratory, Research Institute for Medical Sciences, College of Medicine, Chungnam National University, Daejeon 301-131, South Korea.
authors: Jisoo
authors: J
authors: Park
authors: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Shaanxi, 710032, China.
authors: Yuwen
authors: Y
authors: Li
authors: Department of Neurosurgery, College of Medicine, Chungnam National University, Daejeon 301-747, South Korea.
authors: Seon-Hwan
authors: SH
authors: Kim
authors: Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-333, South Korea.
authors: Keum-Jin
authors: KJ
authors: Yang
authors: Department of Pharmacology, Metabolic Diseases and Cell Signaling Laboratory, Research Institute for Medical Sciences, College of Medicine, Chungnam National University, Daejeon 301-131, South Korea.
authors: Gyeyeong
authors: G
authors: Kong
authors: Department of Pharmacology, Metabolic Diseases and Cell Signaling Laboratory, Research Institute for Medical Sciences, College of Medicine, Chungnam National University, Daejeon 301-131, South Korea.
authors: Robin
authors: R
authors: Shrestha
authors: Department of Pharmacology, Metabolic Diseases and Cell Signaling Laboratory, Research Institute for Medical Sciences, College of Medicine, Chungnam National University, Daejeon 301-131, South Korea.
authors: Quangdon
authors: Q
authors: Tran
authors: Department of Pharmacology, Metabolic Diseases and Cell Signaling Laboratory, Research Institute for Medical Sciences, College of Medicine, Chungnam National University, Daejeon 301-131, South Korea.
authors: Kyeong Ah
authors: KA
authors: Park
authors: Department of Pharmacology, Metabolic Diseases and Cell Signaling Laboratory, Research Institute for Medical Sciences, College of Medicine, Chungnam National University, Daejeon 301-131, South Korea.
authors: Juhee
authors: J
authors: Jeon
authors: Department of Pharmacology, Metabolic Diseases and Cell Signaling Laboratory, Research Institute for Medical Sciences, College of Medicine, Chungnam National University, Daejeon 301-131, South Korea.
authors: Gang Min
authors: GM
authors: Hur
authors: Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-333, South Korea.
authors: Chul-Ho
authors: CH
authors: Lee
authors: Department of Pharmacology, Korea University College of Medicine, Seoul 136-701, South Korea. Electronic address: LDHKIM@korea.ac.kr.
authors: Dong-Hoon
authors: DH
authors: Kim
authors: Metabolic Disease Institute, University of Cincinnati, Cincinnati, OH 45437, USA; Department of Pharmacology, Metabolic Diseases and Cell Signaling Laboratory, Research Institute for Medical Sciences, College of Medicine, Chungnam National University, Daejeon 301-131, South Korea. Electronic address: insulin@cnu.ac.kr.
authors: Jongsun
authors: J
authors: Park
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism; D050154:Adiposity / Q000235:genetics; D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D059305:Diet, High-Fat / Q000379:methods; D015536:Down-Regulation / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D010170:Palmitoyl-CoA Hydrolase; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D013869:Thiolester Hydrolases / Q000235:genetics* / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D007328:Insulin; D008565:Membrane Proteins; D010170:Palmitoyl-CoA Hydrolase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D011972:Receptor, Insulin; D013869:Thiolester Hydrolases; C488528:LETM1 protein, human; C437985:THEM4 protein, human; C527670:CTMP protein, mouse
keywords: CTMP; Insulin signaling; LETM1; Obesity; PKB