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CLC number: Q493

On-line Access: 2016-09-07

Received: 2016-06-18

Revision Accepted: 2016-08-07

Crosschecked: 2016-08-08

Cited: 1

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Citations:  Bibtex RefMan EndNote GB/T7714


Xiao-yang Sun


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Journal of Zhejiang University SCIENCE B 2016 Vol.17 No.9 P.657-671


A disputed evidence on obesity: comparison of the effects of Rcan2−/− and Rps6kb1−/− mutations on growth and body weight in C57BL/6J mice

Author(s):  Jing Zhao, Shi-wei Li, Qian-qian Gong, Ling-cui Ding, Ye-cheng Jin, Jian Zhang, Jian-gang Gao, Xiao-yang Sun

Affiliation(s):  Institute of Developmental Biology, School of Life Science, Shandong University, Jinan 250100, China

Corresponding email(s):   sunxy70@sdu.edu.cn

Key Words:  Rcan2 gene, Rps6kb1 gene, Growth, Body weight regulation, Obesity

Jing Zhao, Shi-wei Li, Qian-qian Gong, Ling-cui Ding, Ye-cheng Jin, Jian Zhang, Jian-gang Gao, Xiao-yang Sun. A disputed evidence on obesity: comparison of the effects of Rcan2−/− and Rps6kb1−/− mutations on growth and body weight in C57BL/6J mice[J]. Journal of Zhejiang University Science B, 2016, 17(9): 657-671.

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author="Jing Zhao, Shi-wei Li, Qian-qian Gong, Ling-cui Ding, Ye-cheng Jin, Jian Zhang, Jian-gang Gao, Xiao-yang Sun",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

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%T A disputed evidence on obesity: comparison of the effects of Rcan2−/− and Rps6kb1−/− mutations on growth and body weight in C57BL/6J mice
%A Jing Zhao
%A Shi-wei Li
%A Qian-qian Gong
%A Ling-cui Ding
%A Ye-cheng Jin
%A Jian Zhang
%A Jian-gang Gao
%A Xiao-yang Sun
%J Journal of Zhejiang University SCIENCE B
%V 17
%N 9
%P 657-671
%@ 1673-1581
%D 2016
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1600276

T1 - A disputed evidence on obesity: comparison of the effects of Rcan2−/− and Rps6kb1−/− mutations on growth and body weight in C57BL/6J mice
A1 - Jing Zhao
A1 - Shi-wei Li
A1 - Qian-qian Gong
A1 - Ling-cui Ding
A1 - Ye-cheng Jin
A1 - Jian Zhang
A1 - Jian-gang Gao
A1 - Xiao-yang Sun
J0 - Journal of Zhejiang University Science B
VL - 17
IS - 9
SP - 657
EP - 671
%@ 1673-1581
Y1 - 2016
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1600276

It is widely accepted that body weight and adipose mass are tightly regulated by homeostatic mechanisms, in which leptin plays a critical role through hypothalamic pathways, and obesity is a result of homeostatic disorder. However, in C57BL/6J mice, we found that Rcan2 increases food intake and plays an important role in the development of age- and diet-induced obesity through a leptin-independent mechanism. RCAN2 was initially identified as a thyroid hormone (T3)-responsive gene in human fibroblasts. Expression of RCAN2 is regulated by T3 through the PI3K-Akt/PKB-mTOR-Rps6kb1 signaling pathway. Intriguingly, both Rcan2−/− and Rps6kb1−/− mutations were reported to result in lean phenotypes in mice. In this study we compared the effects of these two mutations on growth and body weight in C57BL/6J mice. We observed reduced body weight and lower fat mass in both Rcan2−/− and Rps6kb1−/− mice compared to the wild-type mice, and we reported other differences unique to either the Rcan2−/− or Rps6kb1−/− mice. Firstly, loss of Rcan2 does not directly alter body length; however, Rcan2−/− mice exhibit reduced food intake. In contrast, Rps6kb1−/− mice exhibit abnormal embryonic development, which leads to smaller body size and reduced food intake in adulthood. Secondly, when fed a normal chow diet, Rcan2−/− mice weigh significantly more than Rps6kb1−/− mice, but both Rcan2−/− and Rps6kb1−/− mice develop similar amounts of epididymal fat. On a high-fat diet, Rcan2−/− mice gain body weight and fat mass at slower rates than Rps6kb1−/− mice. Finally, using the double-knockout mice (Rcan2−/− Rps6kb1−/−), we demonstrate that concurrent loss of Rcan2 and Rps6kb1 has an additive effect on body weight reduction in C57BL/6J mice. Our data suggest that Rcan2 and Rps6kb1 mutations both affect growth and body weight of mice, though likely through different mechanisms.


方法:在严格控制的饲养条件下,从4周龄开始给野生小鼠、Rcan2−/−小鼠和Rps6kb1−/−小鼠分别喂食普通饲料和高脂肪饲料,连续16周监测小鼠的体重增长曲线。体重监测结束后解剖小鼠并测定其胫骨长、脂肪及肝脏重量,对各组的脂肪和肝脏进行组织学分析和比较。通过野生小鼠和Rcan2−/−小鼠的高脂肪饲料配对喂养实验,确定二者正常摄食条件下的体重差别是否由摄食量不同所致。通过研究双突变(Rcan2−/− Rps6kb1−/−)小鼠与Rps6kb1−/−小鼠的相关指标,进一步确定Rcan2Rps6kb1是否经过不同机制影响体重。


Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


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[51]List of electronic supplementary materials

[52]Table S1 Individual mouse data on NCD

[53]Table S2 Individual mouse data on HFD

[54]Table S3 Individual mouse data for pair-feeding

[55]Table S4 Individual mouse data for double-mutants

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