Abstract
Aim:
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.
Materials and 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.
Conclusion:
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.
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Acknowledgements
This work was supported by the National Health and Medical Research Council of Australia (Project Grants 350313 and 433021, Training Fellowship 1013264) and the Australian Research Council (Grant number LP0883996).
Author contributions
MJ, DC-S and RSW designed the research; SDP, DJR and AH performed the research; EM, DC-S and RSW contributed new reagents/analytical tools; SDP, DPB and RSW analysed the data; SDP, DPB and RSW interpreted the data and drafted the manuscript. EM, DPB, MJ, DC-S and RSW critically reviewed the paper. All authors read and approved the final manuscript.
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Premaratna, S., Manickam, E., Begg, D. et al. Angiotensin-converting enzyme inhibition reverses diet-induced obesity, insulin resistance and inflammation in C57BL/6J mice. Int J Obes 36, 233–243 (2012). https://doi.org/10.1038/ijo.2011.95
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DOI: https://doi.org/10.1038/ijo.2011.95
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