title: [Effects of tumor necrosis factor-alpha induced insulin resistance on adipose triglyceride lipase in mice].
abstract: OBJECTIVE
  To investigate the effects of tumor necrosis factor (TNF)-alpha induced insulin resistance (IR) on glucose and lipid metabolism and adipose triglyceride lipase (ATGL).
  
  
  METHODS
  Forty male C57BL/6J mice were randomly divided into 2 equal groups: TNF-alpha group with undergoing intraperitoneal injection of TNF-alpha 6 microg x kg(-1) x d(-1) for 7 days and normal control (NC) group with saline injection. Hyperinsulinemic-euglycemic clamp technique combined with 2-deoxy-[(3)H] glucose as a tracer was used on 20 mice, 10 from each group, to examine the fasting blood glucose (FBG), plasma insulin (INS), total cholesterol (TC), triglyceride (TG), and free fatty acid (FFA). The glucose infusion rate (GIR) was recorded. Other 20 mice, 10 in each group, were killed with their adipose and/or muscle tissues taken out. RT-PCR was used to detect the mRNA expression of ATGL, hormone-sensitive lipase (HSL), carnitine palmitoyl transferase-1 (CPT-1), and peroxisome proliferator activated receptor-gamma (PPARgamma). Western blotting was used to measure the protein expression of ATGL. Muscle glucose uptake (MGU) was measured.
  
  
  RESULTS
  After TNF-alpha treatment, the FBG, plasma INS, and FFA were significantly elevated in the TNF group compared with the NC group (all P < 0.05). During the steady-state of clamp test, the plasma INS level of the TNF group was (341.7 +/- 17.7) mU/L, significantly higher than that of the NC group [(84.7 +/- 5.5) mU/L, P < 0.01]. The FFA level of the TNF group was (0.82 +/- 0.03) mmol/L, significantly higher than that of the NC group [(0.43 +/- 0.07) mmol/L, P < 0.01]. The GIR of the TNF group was (39.1 +/- 2.3) mg x kg(-1)x min(-1), significantly lower than that of the NC group [(54.2 +/- 2.2) mg x kg(-1) x min(-1), P < 0.01]. The MGU level of the TNF group was (15.8 +/- 1.7) micromol.100 g(-1) x min(-1), significantly lower than that of the NC group [(20.9 +/- 2.5) micromol.100 g(-1) x min(-1), P < 0.01]. The ATGL mRNA expression level in adipose tissues of the TNF group was (0.85 +/- 0.09), significantly lower than that of the NC group (1.37 +/- 0.12, P < 0.01). The ATGL protein expression level of the TNF group was 0.53 +/- 0.03, significantly lower than that of the NC group (0.65 +/- 0.05, P < 0.05). The PPARgamma mRNA expression level in adipose tissues of the TNF group was 0.83 +/- 0.07, significantly lower than that of the NC group (1.07 +/- 0.07, P < 0.05).
  
  
  CONCLUSIONS
  In TNF-alpha induced insulin resistance, AGTL may be involved in the pathways of lipid metabolism.
authors.affiliation: Key Laboratory of Laboratory Medical Diagnostics in Ministry of Education, Department of Clinical Biochemistry, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Yu-Lan
authors.initials: YL
authors.lastname: Cheng
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.forename: Gang-Yi
authors.initials: GY
authors.lastname: Yang
authors.forename: Shao-Chuan
authors.initials: SC
authors.lastname: Shi
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.forename: Xun
authors.initials: X
authors.lastname: Sun
mesh_terms: D000818:Animals; D002265:Carboxylic Ester Hydrolases / Q000096:biosynthesis*; D007333:Insulin Resistance / Q000502:physiology; D008049:Lipase; D050356:Lipid Metabolism / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D000217:Acyltransferases
chemical_list: D002265:Carboxylic Ester Hydrolases; D008049:Lipase; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C494445:PNPLA2 protein, mouse; D000217:Acyltransferases