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 diso...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 develop- ment 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-Rps6kbl signaling pathway. Intriguingly, both Rcan2-/- and Rps6kb1-/- mutations were re- ported 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 Rps6kbl-/- 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 Rcan2and Rps6kbl has an additive effect on body weight reduction in C57BL/6J mice. Our data suggest that Rcan2 and Rps6kbl mutations both affect growth and body weight of mice, though likely through different mechanisms.展开更多
基金Project supported by the National Natural Science Foundation of China(Nos.31140091 and 31371495)Shandong Natural Science Foundation(No.ZR2013CM040),China
文摘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 develop- ment 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-Rps6kbl signaling pathway. Intriguingly, both Rcan2-/- and Rps6kb1-/- mutations were re- ported 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 Rps6kbl-/- 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 Rcan2and Rps6kbl has an additive effect on body weight reduction in C57BL/6J mice. Our data suggest that Rcan2 and Rps6kbl mutations both affect growth and body weight of mice, though likely through different mechanisms.
