title: Angiotensin-converting enzyme inhibition reverses diet-induced obesity, insulin resistance and inflammation in C57BL/6J mice.
abstract: OBJECTIVE
  Angiotensin-converting enzyme (ACE) inhibition can reduce the body weight of mice maintained on a high-fat diet. The current study examined the effect of the ACE inhibitor, captopril (CAP), on the reversal of diet-induced obesity (DIO), insulin resistance and inflammation in mice.
  
  
  METHODS
  DIO was produced in C57BL/6J male mice (n=30) by maintaining animals on a high-fat diet (w/w 21% fat) for 12 weeks. During the subsequent 12-week treatment period, the animals were allowed access to the high-fat diet and either water containing CAP (0.05 mg ml(-1)) or plain tap water (CON, control).
  
  
  RESULTS
  From the first week of treatment, food intake and body weight decreased in CAP-treated mice compared with CON mice. Both peripheral insulin sensitivity and hepatic insulin sensitivity were improved in CAP-treated mice compared with CON mice. CAP-treated mice had decreased absolute and relative liver and epididymal fat weights compared with CON mice. CAP-treated mice had higher plasma adiponectin and lower plasma leptin levels than CON mice. Relative to CON mice, CAP-treated mice had reduced adipose and skeletal muscle monocyte chemoattractant protein 1 (MCP-1), adipose interleukin-6 (IL-6), toll-like receptor 4 (TLR4) and uncoupling protein 2 (UCP2) mRNA expressions. Furthermore, CAP-treated mice had increased peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), long chain acyl-CoA dehydrogenase (LCAD), hormone sensitive lipase (HSL) and decreased lipoprotein lipase (LPL) mRNA expressions in the liver.
  
  
  CONCLUSIONS
  The results of the current study indicate that in mice with DIO, CAP treatment reduced food intake and body weight, improved insulin sensitivity and decreased the mRNA expression of markers of inflammation. Thus, CAP may be a viable treatment for obesity, insulin resistance and inflammation.
authors.affiliation: School of Psychological Science, La Trobe University, Bundoora, Victoria, Australia.
authors.forename: S D
authors.initials: SD
authors.lastname: Premaratna
authors.forename: E
authors.initials: E
authors.lastname: Manickam
authors.forename: D P
authors.initials: DP
authors.lastname: Begg
authors.forename: D J
authors.initials: DJ
authors.lastname: Rayment
authors.forename: A
authors.initials: A
authors.lastname: Hafandi
authors.forename: M
authors.initials: M
authors.lastname: Jois
authors.forename: D
authors.initials: D
authors.lastname: Cameron-Smith
authors.forename: R S
authors.initials: RS
authors.lastname: Weisinger
mesh_terms: D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000378:metabolism; D052242:Adiponectin / Q000097:blood; D000273:Adipose Tissue / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001835:Body Weight; D002216:Captopril / Q000494:pharmacology*; D018932:Chemokine CCL2 / Q000378:metabolism; D059305:Diet, High-Fat; D005786:Gene Expression Regulation / Q000187:drug effects; D005951:Glucose Tolerance Test; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000378:metabolism; D007473:Ion Channels / Q000378:metabolism; D020738:Leptin / Q000097:blood; D050356:Lipid Metabolism / Q000187:drug effects*; D008071:Lipoprotein Lipase / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D009765:Obesity / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D002787:Sterol Esterase / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors; D000071246:Uncoupling Protein 2
chemical_list: D052242:Adiponectin; D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D015850:Interleukin-6; D007473:Ion Channels; D020738:Leptin; D024101:Mitochondrial Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D015534:Trans-Activators; D014157:Transcription Factors; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2; D002216:Captopril; D044942:Acyl-CoA Dehydrogenase, Long-Chain; D002787:Sterol Esterase; D008071:Lipoprotein Lipase