Polymyxin B and related cyclic peptides facilitate leanness and reduce fat mass and triglyceride content in ageing rats: Potential prototype drugs against obesity

Yoram Shechter, Marina Mironchik, Shimon Amir, Ben Ami Sela, Haim Tsubery, Hailin Zheng, Mati Fridkin

Research output: Contribution to journalArticlepeer-review

Abstract

Polymyxin B (PMXB) blocks the action of insulin on glucose uptake in vitro. In vivo, it reverses hypoglycemia induced by exogenous insulin. Here we have treated mature male rats daily with PMXB over a period of two weeks. This therapy has decreased body weight by 11%, adipose fat mass by 46% and triglyceride levels by 39%, with no indication of liver or kidney toxicity. Two suboptimal parameters, however, were a decrease in food intake in the first week of treatment and some increase in fasting glucose levels. We have screened for PMXB-analogs having less associating affinity with rat-muscle phospholipids, and revealed that the same therapy using PMXB-derived peptide (nona-PMXB) is most optimal. This PMXB-analog is devoid of antibacterial activity and is four times less toxic than PMXB. Nona-PMXB therapy lower by 10, 32, 35 and 6% body weight gain, fat mass, circulating triglycerides and fasting glucose levels, respectively, in spite of normal or even elevated food intake in nona-PMXB treated rats. In summary, we found that nona-PMXB therapy is capable if inducing leanness in mature rats, particularly at the expense of decreasing fat-mass in adipose tissue. By and large, we suggest that lowering the action of insulin, on fat build-up solely, may be a therapeutically feasible task to fight with human adiposity in the future.

Original languageEnglish
Pages (from-to)121-129
Number of pages9
JournalInternational Journal of Peptide Research and Therapeutics
Volume12
Issue number2
DOIs
StatePublished - Jun 2006
Externally publishedYes

Keywords

  • Insulin
  • Obesity
  • Polymyxin B

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