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Rapamycin-induced metabolic defects are reversible in both lean and obese mice

The inhibition of mTOR (mechanistic target of rapamycin) by the macrolide rapamycin has many beneficial effects in mice, including extension of lifespan and reduction or prevention of several age-related diseases. At the same time, chronic rapamycin treatment causes impairments in glucose metabolism...

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Autores principales: Liu, Yuhong, Diaz, Vivian, Fernandez, Elizabeth, Strong, Randy, Ye, Lan, Baur, Joseph A., Lamming, Dudley W., Richardson, Arlan, Salmon, Adam B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4221917/
https://www.ncbi.nlm.nih.gov/pubmed/25324470
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author Liu, Yuhong
Diaz, Vivian
Fernandez, Elizabeth
Strong, Randy
Ye, Lan
Baur, Joseph A.
Lamming, Dudley W.
Richardson, Arlan
Salmon, Adam B.
author_facet Liu, Yuhong
Diaz, Vivian
Fernandez, Elizabeth
Strong, Randy
Ye, Lan
Baur, Joseph A.
Lamming, Dudley W.
Richardson, Arlan
Salmon, Adam B.
author_sort Liu, Yuhong
collection PubMed
description The inhibition of mTOR (mechanistic target of rapamycin) by the macrolide rapamycin has many beneficial effects in mice, including extension of lifespan and reduction or prevention of several age-related diseases. At the same time, chronic rapamycin treatment causes impairments in glucose metabolism including hyperglycemia, glucose intolerance and insulin resistance. It is unknown whether these metabolic effects of rapamycin are permanent or whether they can be alleviated. Here, we confirmed that rapamycin causes glucose intolerance and insulin resistance in both inbred and genetically heterogeneous mice fed either low fat or high fat diets, suggesting that these effects of rapamycin are independent of genetic background. Importantly, we also found that these effects were almost completely lost within a few weeks of cessation of treatment, showing that chronic rapamycin treatment does not induce permanent impairment of glucose metabolism. Somewhat surprisingly, chronic rapamycin also promoted increased accumulation of adipose tissue in high fat fed mice. However, this effect too was lost when rapamycin treatment was ended suggesting that this effect of rapamycin is also not permanent. The reversible nature of rapamycin's alterations of metabolic function suggests that these potentially detrimental side-effects might be managed through alternative dosing strategies or concurrent treatment options.
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spelling pubmed-42219172014-11-07 Rapamycin-induced metabolic defects are reversible in both lean and obese mice Liu, Yuhong Diaz, Vivian Fernandez, Elizabeth Strong, Randy Ye, Lan Baur, Joseph A. Lamming, Dudley W. Richardson, Arlan Salmon, Adam B. Aging (Albany NY) Research Paper The inhibition of mTOR (mechanistic target of rapamycin) by the macrolide rapamycin has many beneficial effects in mice, including extension of lifespan and reduction or prevention of several age-related diseases. At the same time, chronic rapamycin treatment causes impairments in glucose metabolism including hyperglycemia, glucose intolerance and insulin resistance. It is unknown whether these metabolic effects of rapamycin are permanent or whether they can be alleviated. Here, we confirmed that rapamycin causes glucose intolerance and insulin resistance in both inbred and genetically heterogeneous mice fed either low fat or high fat diets, suggesting that these effects of rapamycin are independent of genetic background. Importantly, we also found that these effects were almost completely lost within a few weeks of cessation of treatment, showing that chronic rapamycin treatment does not induce permanent impairment of glucose metabolism. Somewhat surprisingly, chronic rapamycin also promoted increased accumulation of adipose tissue in high fat fed mice. However, this effect too was lost when rapamycin treatment was ended suggesting that this effect of rapamycin is also not permanent. The reversible nature of rapamycin's alterations of metabolic function suggests that these potentially detrimental side-effects might be managed through alternative dosing strategies or concurrent treatment options. Impact Journals LLC 2014-09-02 /pmc/articles/PMC4221917/ /pubmed/25324470 Text en Copyright: © 2014 Liu et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
spellingShingle Research Paper
Liu, Yuhong
Diaz, Vivian
Fernandez, Elizabeth
Strong, Randy
Ye, Lan
Baur, Joseph A.
Lamming, Dudley W.
Richardson, Arlan
Salmon, Adam B.
Rapamycin-induced metabolic defects are reversible in both lean and obese mice
title Rapamycin-induced metabolic defects are reversible in both lean and obese mice
title_full Rapamycin-induced metabolic defects are reversible in both lean and obese mice
title_fullStr Rapamycin-induced metabolic defects are reversible in both lean and obese mice
title_full_unstemmed Rapamycin-induced metabolic defects are reversible in both lean and obese mice
title_short Rapamycin-induced metabolic defects are reversible in both lean and obese mice
title_sort rapamycin-induced metabolic defects are reversible in both lean and obese mice
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4221917/
https://www.ncbi.nlm.nih.gov/pubmed/25324470
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