The Role of Insulin and Insulin-Like Growth Factor-1/FoxO-Mediated Transcription for the Pathogenesis of Obesity-Associated Dementia

Epidemiological studies suggest that being obese in midlife is a risk factor for cognitive decline and dementia in later life. Hyperinsulinemia is one of the most frequent endocrine features in overweight people which results in insulin desensitization. Thus, chronically high insulin levels have bee...

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Main Authors:	Moll, Lorna, Schubert, Markus
Format:	Online
Language:	English
Published:	Hindawi Publishing Corporation 2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3359655/

id	pubmed-3359655
recordtype	oai_dc
spelling	pubmed-33596552012-05-31 The Role of Insulin and Insulin-Like Growth Factor-1/FoxO-Mediated Transcription for the Pathogenesis of Obesity-Associated Dementia Moll, Lorna Schubert, Markus Review Article Epidemiological studies suggest that being obese in midlife is a risk factor for cognitive decline and dementia in later life. Hyperinsulinemia is one of the most frequent endocrine features in overweight people which results in insulin desensitization. Thus, chronically high insulin levels have been identified as risk factor for dementia. Accordingly, chronically high insulin levels might be harmful for brain function. Furthermore, insulin and IGF-1-induced signaling is reduced in the brains of patients suffering from Alzheimer's disease (AD). Interestingly, studies in rodents suggest that reduced insulin receptor (IR) and insulin-like growth factor-1 receptor (IGF-1R) signaling decrease AD pathology, that is, β-amyloid toxicity. Data obtained in C. elegans indicate that the beneficial effect mediated via reduced IR/IGF-1R signaling might partially be induced via the forkhead-box O transcription factors (FoxO). In the mammalian brain, there are FoxO1, FoxO3a, and FoxO6 expressed. Surprisingly, high-fat diet specifically reduces the expression of FoxO3a and FoxO6 suggesting that IR/IGF-1 → FoxO-mediated transcription is involved in the pathogenesis of obesity-associated cognitive impairment. Therefore, the function of FoxO1 and FoxO3a has been investigated in animal models of Alzheimer's disease in detail. The current paper focuses on the role of IR/IGF-1 signaling and IR/IGF-1 → FoxO-mediated transcription for the pathogenesis of obesity-associated dementia. Hindawi Publishing Corporation 2012 2012-05-13 /pmc/articles/PMC3359655/ /pubmed/22654904 http://dx.doi.org/10.1155/2012/384094 Text en Copyright © 2012 L. Moll and M. Schubert. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Moll, Lorna Schubert, Markus
spellingShingle	Moll, Lorna Schubert, Markus The Role of Insulin and Insulin-Like Growth Factor-1/FoxO-Mediated Transcription for the Pathogenesis of Obesity-Associated Dementia
author_facet	Moll, Lorna Schubert, Markus
author_sort	Moll, Lorna
title	The Role of Insulin and Insulin-Like Growth Factor-1/FoxO-Mediated Transcription for the Pathogenesis of Obesity-Associated Dementia
title_short	The Role of Insulin and Insulin-Like Growth Factor-1/FoxO-Mediated Transcription for the Pathogenesis of Obesity-Associated Dementia
title_full	The Role of Insulin and Insulin-Like Growth Factor-1/FoxO-Mediated Transcription for the Pathogenesis of Obesity-Associated Dementia
title_fullStr	The Role of Insulin and Insulin-Like Growth Factor-1/FoxO-Mediated Transcription for the Pathogenesis of Obesity-Associated Dementia
title_full_unstemmed	The Role of Insulin and Insulin-Like Growth Factor-1/FoxO-Mediated Transcription for the Pathogenesis of Obesity-Associated Dementia
title_sort	role of insulin and insulin-like growth factor-1/foxo-mediated transcription for the pathogenesis of obesity-associated dementia
description	Epidemiological studies suggest that being obese in midlife is a risk factor for cognitive decline and dementia in later life. Hyperinsulinemia is one of the most frequent endocrine features in overweight people which results in insulin desensitization. Thus, chronically high insulin levels have been identified as risk factor for dementia. Accordingly, chronically high insulin levels might be harmful for brain function. Furthermore, insulin and IGF-1-induced signaling is reduced in the brains of patients suffering from Alzheimer's disease (AD). Interestingly, studies in rodents suggest that reduced insulin receptor (IR) and insulin-like growth factor-1 receptor (IGF-1R) signaling decrease AD pathology, that is, β-amyloid toxicity. Data obtained in C. elegans indicate that the beneficial effect mediated via reduced IR/IGF-1R signaling might partially be induced via the forkhead-box O transcription factors (FoxO). In the mammalian brain, there are FoxO1, FoxO3a, and FoxO6 expressed. Surprisingly, high-fat diet specifically reduces the expression of FoxO3a and FoxO6 suggesting that IR/IGF-1 → FoxO-mediated transcription is involved in the pathogenesis of obesity-associated cognitive impairment. Therefore, the function of FoxO1 and FoxO3a has been investigated in animal models of Alzheimer's disease in detail. The current paper focuses on the role of IR/IGF-1 signaling and IR/IGF-1 → FoxO-mediated transcription for the pathogenesis of obesity-associated dementia.
publisher	Hindawi Publishing Corporation
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3359655/
_version_	1611532212324270080

The Role of Insulin and Insulin-Like Growth Factor-1/FoxO-Mediated Transcription for the Pathogenesis of Obesity-Associated Dementia

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