Skip to main content

Main menu

  • Home
  • Articles
    • Current
    • Special Feature Articles - Most Recent
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • List of Issues
  • Front Matter
    • Front Matter Portal
    • Journal Club
  • News
    • For the Press
    • This Week In PNAS
    • PNAS in the News
  • Podcasts
  • Authors
    • Information for Authors
    • Editorial and Journal Policies
    • Submission Procedures
    • Fees and Licenses
  • Submit
  • Submit
  • About
    • Editorial Board
    • PNAS Staff
    • FAQ
    • Accessibility Statement
    • Rights and Permissions
    • Site Map
  • Contact
  • Journal Club
  • Subscribe
    • Subscription Rates
    • Subscriptions FAQ
    • Open Access
    • Recommend PNAS to Your Librarian

User menu

  • Log in
  • My Cart

Search

  • Advanced search
Home
Home
  • Log in
  • My Cart

Advanced Search

  • Home
  • Articles
    • Current
    • Special Feature Articles - Most Recent
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • List of Issues
  • Front Matter
    • Front Matter Portal
    • Journal Club
  • News
    • For the Press
    • This Week In PNAS
    • PNAS in the News
  • Podcasts
  • Authors
    • Information for Authors
    • Editorial and Journal Policies
    • Submission Procedures
    • Fees and Licenses
  • Submit
Research Article

Extended lifespan and reduced adiposity in mice lacking the FAT10 gene

Allon Canaan, Jason DeFuria, Eddie Perelman, Vincent Schultz, Montrell Seay, David Tuck, Richard A. Flavell, Michael P. Snyder, Martin S. Obin, and Sherman M. Weissman
  1. Departments of aGenetics,
  2. dPediatrics,
  3. ePathology, and
  4. fImmunobiology, Yale University School of Medicine, New Haven, CT 06520;
  5. bObesity and Metabolism Laboratory, Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111;
  6. cDepartment of Biotechnology Engineering, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel; and
  7. gDepartment of Genetics, Stanford University, Stanford, CA 94305

See allHide authors and affiliations

PNAS first published March 24, 2014; https://doi.org/10.1073/pnas.1323426111
Allon Canaan
Departments of aGenetics,
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: allon.canaan@yale.edu
Jason DeFuria
bObesity and Metabolism Laboratory, Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Eddie Perelman
cDepartment of Biotechnology Engineering, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Vincent Schultz
dPediatrics,
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Montrell Seay
Departments of aGenetics,
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David Tuck
ePathology, and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Richard A. Flavell
fImmunobiology, Yale University School of Medicine, New Haven, CT 06520;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael P. Snyder
gDepartment of Genetics, Stanford University, Stanford, CA 94305
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Martin S. Obin
bObesity and Metabolism Laboratory, Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sherman M. Weissman
Departments of aGenetics,
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: allon.canaan@yale.edu
  1. Contributed by Sherman M. Weissman, December 24, 2013 (sent for review October 29, 2013)

  • Article
  • Figures & SI
  • Info & Metrics
  • PDF
Loading

Significance

For the first time we describe a physiological role for HLA-F adjacent transcript 10 (FAT10) in metabolism, obesity, and aging in mammals. We show that FAT10 knockout prevents the development of age-associated obesity in mice while extending lifespan and vigor without the appearance of deleterious developmental effects. In addition, we did not observe an increase in cancer incidence. If the role of FAT10 in humans is similar to mice, then targeting of FAT10 may hold promising therapeutic impact for the treatment of various diseases including obesity and obesity-related diseases and aging associated diseases.

Abstract

The HLA-F adjacent transcript 10 (FAT10) is a member of the ubiquitin-like gene family that alters protein function/stability through covalent ligation. Although FAT10 is induced by inflammatory mediators and implicated in immunity, the physiological functions of FAT10 are poorly defined. We report the discovery that FAT10 regulates lifespan through pleiotropic actions on metabolism and inflammation. Median and overall lifespan are increased 20% in FAT10ko mice, coincident with elevated metabolic rate, preferential use of fat as fuel, and dramatically reduced adiposity. This phenotype is associated with metabolic reprogramming of skeletal muscle (i.e., increased AMP kinase activity, β-oxidation and -uncoupling, and decreased triglyceride content). Moreover, knockout mice have reduced circulating glucose and insulin levels and enhanced insulin sensitivity in metabolic tissues, consistent with elevated IL-10 in skeletal muscle and serum. These observations suggest novel roles of FAT10 in immune metabolic regulation that impact aging and chronic disease.

  • longevity
  • obesity
  • mammals

Footnotes

  • ↵1A.C. and J.D. contributed equally to this work.

  • ↵2To whom correspondence should be addressed. E-mail: allon.canaan{at}yale.edu.
  • Author contributions: A.C., M.S.O., and S.M.W. designed research; A.C., J.D., and M.S. performed research; R.A.F. and M.P.S. contributed new reagents/analytic tools; A.C., J.D., E.P., V.S., D.T., R.A.F., M.S.O., and S.M.W. analyzed data; A.C., M.S.O., and S.M.W. wrote the paper; and A.C. discovered the mouse phenotype.

  • The authors declare no conflict of interest.

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1323426111/-/DCSupplemental.

Next
Back to top
Article Alerts
Email Article

Thank you for your interest in spreading the word on PNAS.

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.
Extended lifespan and reduced adiposity in mice lacking the FAT10 gene
(Your Name) has sent you a message from PNAS
(Your Name) thought you would like to see the PNAS web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
FAT10 impacts adiposity and aging
Allon Canaan, Jason DeFuria, Eddie Perelman, Vincent Schultz, Montrell Seay, David Tuck, Richard A. Flavell, Michael P. Snyder, Martin S. Obin, Sherman M. Weissman
Proceedings of the National Academy of Sciences Mar 2014, 201323426; DOI: 10.1073/pnas.1323426111

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Request Permissions
Share
FAT10 impacts adiposity and aging
Allon Canaan, Jason DeFuria, Eddie Perelman, Vincent Schultz, Montrell Seay, David Tuck, Richard A. Flavell, Michael P. Snyder, Martin S. Obin, Sherman M. Weissman
Proceedings of the National Academy of Sciences Mar 2014, 201323426; DOI: 10.1073/pnas.1323426111
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Mendeley logo Mendeley
Proceedings of the National Academy of Sciences: 118 (15)
Current Issue

Submit

Sign up for Article Alerts

Jump to section

  • Article
  • Figures & SI
  • Info & Metrics
  • PDF

You May Also be Interested in

Water from a faucet fills a glass.
News Feature: How “forever chemicals” might impair the immune system
Researchers are exploring whether these ubiquitous fluorinated molecules might worsen infections or hamper vaccine effectiveness.
Image credit: Shutterstock/Dmitry Naumov.
Reflection of clouds in the still waters of Mono Lake in California.
Inner Workings: Making headway with the mysteries of life’s origins
Recent experiments and simulations are starting to answer some fundamental questions about how life came to be.
Image credit: Shutterstock/Radoslaw Lecyk.
Cave in coastal Kenya with tree growing in the middle.
Journal Club: Small, sharp blades mark shift from Middle to Later Stone Age in coastal Kenya
Archaeologists have long tried to define the transition between the two time periods.
Image credit: Ceri Shipton.
Illustration of groups of people chatting
Exploring the length of human conversations
Adam Mastroianni and Daniel Gilbert explore why conversations almost never end when people want them to.
Listen
Past PodcastsSubscribe
Panda bear hanging in a tree
How horse manure helps giant pandas tolerate cold
A study finds that giant pandas roll in horse manure to increase their cold tolerance.
Image credit: Fuwen Wei.

Similar Articles

Site Logo
Powered by HighWire
  • Submit Manuscript
  • Twitter
  • Facebook
  • RSS Feeds
  • Email Alerts

Articles

  • Current Issue
  • Special Feature Articles – Most Recent
  • List of Issues

PNAS Portals

  • Anthropology
  • Chemistry
  • Classics
  • Front Matter
  • Physics
  • Sustainability Science
  • Teaching Resources

Information

  • Authors
  • Editorial Board
  • Reviewers
  • Subscribers
  • Librarians
  • Press
  • Cozzarelli Prize
  • Site Map
  • PNAS Updates
  • FAQs
  • Accessibility Statement
  • Rights & Permissions
  • About
  • Contact

Feedback    Privacy/Legal

Copyright © 2021 National Academy of Sciences. Online ISSN 1091-6490