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| A disputed evidence on obesity: comparison of the effects of Rcan2−/− and Rps6kb1−/− mutations on growth and body weight in C57BL/6J mice |
| Jing Zhao, Shi-wei Li, Qian-qian Gong, Ling-cui Ding, Ye-cheng Jin, Jian Zhang, Jian-gang Gao, Xiao-yang Sun |
| Institute of Developmental Biology, School of Life Science, Shandong University, Jinan 250100, China |
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Abstract 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.
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Received: 18 June 2016
Published: 07 September 2016
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