The Fat Mass- and Obesity-Associated (FTO) Gene to Obesity: Lessons from Mouse Models

Jeong Yoon Chang, Joo Hyun Park, Sung Eun Park, Jinyoung Shon, Yoon Jung Park

Research output: Contribution to journalReview articlepeer-review

21 Scopus citations

Abstract

Objective: Genetic variants at the fat mass- and obesity-associated (FTO) locus are strongly associated with obesity-related traits by regulating neighboring genes. Nevertheless, it is possible that FTO protein is directly involved in mechanisms regulating body composition and adiposity. Here, the in vivo biological functions of FTO in the risk for obesity were studied by reviewing murine models. Methods: The effects of the locus-specific manipulations of the murine Fto gene on metabolic-related phenotypes in genetically modified mouse models were reviewed and summarized into the following three categories: growth and body composition, eating behaviors, and metabolic homeostasis. Results: The mouse models showed different phenotypes depending on target tissues and methods for gene manipulation. Mice harboring deletions or point mutations at the Fto locus had high metabolic rates, while FTO-overexpressing mice showed dyslipidemia. Both deletion and overexpression of the Fto gene led to abnormal eating behaviors. Intriguingly, several phenotypes were differently expressed depending on developmental timing of the genetic manipulations. For instance, a germ line deletion decreased total body fat mass, while the deletion in adult mice increased it. Conclusions: The results highlight that FTO is critical not only for body composition but also normal development, and its function might differ depending on the stage of development.

Original languageEnglish
Pages (from-to)1674-1686
Number of pages13
JournalObesity
Volume26
Issue number11
DOIs
StatePublished - Nov 2018

Bibliographical note

Funding Information:
Funding agencies: This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (2018R1D1A1B07051274). JS and JHP were supported by Brain Korea 21 PLUS Project (22A20130012143), and JS was supported by Chung Mong-Koo Foundation. Disclosure: The authors declared no conflict of interest. Author contributions: YJP and JYC conceived the concept and designed the analysis. JYC, JHP, and JS performed the analysis. JYC, SEP, JHP, and YJP wrote the paper. Received: 12 April 2018; Accepted: 10 August 2018; Published online 25 October 2018. doi:10.1002/oby.22301

Funding Information:
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (2018R1D1A1B07051274). JS and JHP were supported by Brain Korea 21 PLUS Project (22A20130012143), and JS was supported by Chung Mong-Koo Foundation.

Publisher Copyright:
© 2018 The Obesity Society

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