RRC ID 47251
Author Zhao J, Li SW, Gong QQ, Ding LC, Jin YC, Zhang J, Gao JG, Sun XY.
Title A disputed evidence on obesity: comparison of the effects of Rcan2(-/-) and Rps6kb1(-/-) mutations on growth and body weight in C57BL/6J mice.
Journal J Zhejiang Univ Sci B
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.
Volume 17(9)
Pages 657-71
Published 2016-9-1
DOI 10.1631/jzus.B1600276
PMID 27604858
PMC PMC5018613
MeSH Adipose Tissue / metabolism Animals Animals, Newborn Birth Weight Body Composition Body Size Body Weight Epididymis / metabolism Female Fibroblasts / metabolism Genotype Homeostasis Intracellular Signaling Peptides and Proteins Male Mice Mice, Inbred C57BL Mice, Knockout Mutation Obesity / genetics* Phenotype Proteins / genetics* Ribosomal Protein S6 Kinases, 70-kDa / genetics* Triiodothyronine
IF 2.082
Times Cited 1
WOS Category BIOCHEMISTRY & MOLECULAR BIOLOGY BIOTECHNOLOGY & APPLIED MICROBIOLOGY MEDICINE, RESEARCH & EXPERIMENTAL
Resource
Mice RBRC02385 RBRC04891