Skip to main content
  • More from ADA
    • Diabetes Care
    • Clinical Diabetes
    • Diabetes Spectrum
    • ADA Standards of Medical Care in Diabetes
    • ADA Scientific Sessions Abstracts
    • BMJ Open Diabetes Research & Care
  • Subscribe
  • Log in
  • Log out
  • My Cart
  • Follow ada on Twitter
  • RSS
  • Visit ada on Facebook
Diabetes

Advanced Search

Main menu

  • Home
  • Current
    • Current Issue
    • Online Ahead of Print
    • ADA Scientific Sessions Abstracts
  • Browse
    • By Topic
    • Issue Archive
    • Saved Searches
    • ADA Scientific Sessions Abstracts
    • Diabetes COVID-19 Article Collection
    • Diabetes Symposium 2020
  • Info
    • About the Journal
    • About the Editors
    • ADA Journal Policies
    • Instructions for Authors
    • Guidance for Reviewers
  • Reprints/Reuse
  • Advertising
  • Subscriptions
    • Individual Subscriptions
    • Institutional Subscriptions and Site Licenses
    • Access Institutional Usage Reports
    • Purchase Single Issues
  • Alerts
    • E­mail Alerts
    • RSS Feeds
  • Podcasts
    • Diabetes Core Update
    • Special Podcast Series: Therapeutic Inertia
    • Special Podcast Series: Influenza Podcasts
    • Special Podcast Series: SGLT2 Inhibitors
    • Special Podcast Series: COVID-19
  • Submit
    • Submit a Manuscript
    • Submit Cover Art
    • ADA Journal Policies
    • Instructions for Authors
    • ADA Peer Review
  • More from ADA
    • Diabetes Care
    • Clinical Diabetes
    • Diabetes Spectrum
    • ADA Standards of Medical Care in Diabetes
    • ADA Scientific Sessions Abstracts
    • BMJ Open Diabetes Research & Care

User menu

  • Subscribe
  • Log in
  • Log out
  • My Cart

Search

  • Advanced search
Diabetes
  • Home
  • Current
    • Current Issue
    • Online Ahead of Print
    • ADA Scientific Sessions Abstracts
  • Browse
    • By Topic
    • Issue Archive
    • Saved Searches
    • ADA Scientific Sessions Abstracts
    • Diabetes COVID-19 Article Collection
    • Diabetes Symposium 2020
  • Info
    • About the Journal
    • About the Editors
    • ADA Journal Policies
    • Instructions for Authors
    • Guidance for Reviewers
  • Reprints/Reuse
  • Advertising
  • Subscriptions
    • Individual Subscriptions
    • Institutional Subscriptions and Site Licenses
    • Access Institutional Usage Reports
    • Purchase Single Issues
  • Alerts
    • E­mail Alerts
    • RSS Feeds
  • Podcasts
    • Diabetes Core Update
    • Special Podcast Series: Therapeutic Inertia
    • Special Podcast Series: Influenza Podcasts
    • Special Podcast Series: SGLT2 Inhibitors
    • Special Podcast Series: COVID-19
  • Submit
    • Submit a Manuscript
    • Submit Cover Art
    • ADA Journal Policies
    • Instructions for Authors
    • ADA Peer Review
Obesity Studies

Loss-of-Function Mutation in Toll-Like Receptor 4 Prevents Diet-Induced Obesity and Insulin Resistance

  1. Daniela M.L. Tsukumo1,
  2. Marco A. Carvalho-Filho1,
  3. José B.C. Carvalheira1,
  4. Patrícia O. Prada1,
  5. Sandro M. Hirabara2,
  6. André A. Schenka3,
  7. Eliana P. Araújo1,
  8. José Vassallo3,
  9. Rui Curi2,
  10. Lício A. Velloso1 and
  11. Mario J.A. Saad1
  1. 1Department of Internal Medicine, State University of Campinas, Campinas, São Paulo, Brazil
  2. 2Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
  3. 3Department of Pathology, State University of Campinas, Campinas, São Paulo, Brazil
  1. Address correspondence and reprint requests to Mario J.A. Saad, MD, Departamento de Clínica Médica, FCM-UNICAMP, Cidade Universitária Zeferino Vaz, Campinas, SP, Brazil, 13081-970. E-mail: msaad{at}fcm.unicamp.br
Diabetes 2007 Aug; 56(8): 1986-1998. https://doi.org/10.2337/db06-1595
PreviousNext
  • Article
  • Figures & Tables
  • Suppl Material
  • Info & Metrics
  • PDF
Loading

This article has a correction, but has also been retracted. Please see:

  • Expression of Concern - March 01, 2015
  • Statement of Retraction. Loss-of-Function Mutation in Toll-Like Receptor 4 Prevents Diet-Induced Obesity and Insulin Resistance. Diabetes 2007;56:1986–1998. DOI: 10.2337/db06-1595 - April 01, 2016

Abstract

Obesity is associated with insulin resistance and a state of abnormal inflammatory response. The Toll-like receptor (TLR)4 has an important role in inflammation and immunity, and its expression has been reported in most tissues of the body, including the insulin-sensitive ones. Because it is activated by lipopolysaccharide and saturated fatty acids, which are inducers of insulin resistance, TLR4 may be a candidate for participation in the cross-talk between inflammatory and metabolic signals. Here, we show that C3H/HeJ mice, which have a loss-of-function mutation in TLR4, are protected against the development of diet-induced obesity. In addition, these mice demonstrate decreased adiposity, increased oxygen consumption, a decreased respiratory exchange ratio, improved insulin sensitivity, and enhanced insulin-signaling capacity in adipose tissue, muscle, and liver compared with control mice during high-fat feeding. Moreover, in these tissues, control mice fed a high-fat diet show an increase in IκB kinase complex and c-Jun NH2-terminal kinase activity, which is prevented in C3H/HeJ mice. In isolated muscles from C3H/HeJ mice, protection from saturated fatty acid–induced insulin resistance is observed. Thus, TLR4 appears to be an important mediator of obesity and insulin resistance and a potential target for the therapy of these highly prevalent medical conditions.

  • CLS, crown-like structure
  • ELISA, enzyme-linked immunosorbent assay
  • FFA, free fatty acid
  • HFD, high-fat diet
  • IGTT, intraperitoneal glucose tolerance test
  • IκBα, inhibitor of nuclear factor-κB
  • IKKβ, IκB kinase complex
  • IL, interleukin
  • IR, insulin receptor
  • IRS-1, insulin receptor substrate-1
  • JNK, c-Jun NH2-terminal kinase
  • LPS, lipopolysaccharide
  • NK-κB, nuclear factor-κB
  • RER, respiratory exchange ratio
  • TNF, tumor necrosis factor
  • TLR, Toll-like receptor
  • WAT, white adipose tissue
  • Received November 14, 2006.
  • Accepted May 18, 2007.
  • DIABETES
View Full Text
PreviousNext
Back to top

In this Issue

August 2007, 56(8)
  • Table of Contents
  • Index by Author
Sign up to receive current issue alerts
View Selected Citations (0)
Print
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word about Diabetes.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Loss-of-Function Mutation in Toll-Like Receptor 4 Prevents Diet-Induced Obesity and Insulin Resistance
(Your Name) has forwarded a page to you from Diabetes
(Your Name) thought you would like to see this page from the Diabetes web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Loss-of-Function Mutation in Toll-Like Receptor 4 Prevents Diet-Induced Obesity and Insulin Resistance
Daniela M.L. Tsukumo, Marco A. Carvalho-Filho, José B.C. Carvalheira, Patrícia O. Prada, Sandro M. Hirabara, André A. Schenka, Eliana P. Araújo, José Vassallo, Rui Curi, Lício A. Velloso, Mario J.A. Saad
Diabetes Aug 2007, 56 (8) 1986-1998; DOI: 10.2337/db06-1595

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Add to Selected Citations
Share

Loss-of-Function Mutation in Toll-Like Receptor 4 Prevents Diet-Induced Obesity and Insulin Resistance
Daniela M.L. Tsukumo, Marco A. Carvalho-Filho, José B.C. Carvalheira, Patrícia O. Prada, Sandro M. Hirabara, André A. Schenka, Eliana P. Araújo, José Vassallo, Rui Curi, Lício A. Velloso, Mario J.A. Saad
Diabetes Aug 2007, 56 (8) 1986-1998; DOI: 10.2337/db06-1595
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Keywords

CLS, crown-like structure
ELISA, enzyme-linked immunosorbent assay
FFA, free fatty acid
HFD, high-fat diet
IGTT, intraperitoneal glucose tolerance test
IκBα, inhibitor of nuclear factor-κB
IKKβ, IκB kinase complex
IL, interleukin
IR, insulin receptor
IRS-1, insulin receptor substrate-1
JNK, c-Jun NH2-terminal kinase
LPS, lipopolysaccharide
NK-κB, nuclear factor-κB
RER, respiratory exchange ratio
TNF, tumor necrosis factor
TLR, Toll-like receptor
WAT, white adipose tissue

Jump to section

  • Article
    • Abstract
    • RESEARCH DESIGN AND METHODS
    • RESULTS
    • DISCUSSION
    • Footnotes
    • REFERENCES
  • Figures & Tables
  • Suppl Material
  • Info & Metrics
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Glucose Sensing Mediated by Portal Glucagon-Like Peptide 1 Receptor Is Markedly Impaired in Insulin-Resistant Obese Animals
  • Muscular G9a Regulates Muscle-Liver-Fat Axis by Musclin Under Overnutrition in Female Mice
  • Manipulation of Dietary Amino Acids Prevents and Reverses Obesity in Mice Through Multiple Mechanisms That Modulate Energy Homeostasis
Show more Obesity Studies

Similar Articles

Navigate

  • Current Issue
  • Online Ahead of Print
  • Scientific Sessions Abstracts
  • Collections
  • Archives
  • Submit
  • Subscribe
  • Email Alerts
  • RSS Feeds

More Information

  • About the Journal
  • Instructions for Authors
  • Journal Policies
  • Reprints and Permissions
  • Advertising
  • Privacy Policy: ADA Journals
  • Copyright Notice/Public Access Policy
  • Contact Us

Other ADA Resources

  • Diabetes Care
  • Clinical Diabetes
  • Diabetes Spectrum
  • Scientific Sessions Abstracts
  • Standards of Medical Care in Diabetes
  • BMJ Open - Diabetes Research & Care
  • Professional Books
  • Diabetes Forecast

 

  • DiabetesJournals.org
  • Diabetes Core Update
  • ADA's DiabetesPro
  • ADA Member Directory
  • Diabetes.org

© 2021 by the American Diabetes Association. Diabetes Print ISSN: 0012-1797, Online ISSN: 1939-327X.