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- Title
1935-P: Loss of µ-Crystallin Increases Adipose Tissues with Inhibitory Effects on Adipocyte Differentiation through ß-Catenin-Dependent Mechanisms in High-Fat Diet Fed Mice.
- Authors
OHKUBO, YOHSUKE; NISHIO, SHIN-ICHI; SHIMADA, YASUHO; KUBOTA, SATOSHI; KITAHARA, JUNICHIRO; SHIBATA, YUSUKE; KITAJIMA, KOHEI; SEKIDO, TAKASHI; SUZUKI, SATORU; KOMATSU, MITSUHISA
- Abstract
The 3,5,3'-triiodo-L-thyronine (T3) binding protein, μ-crystalin (CRYM), regulates intracellular thyroid hormone action by controlling the concentration of T3 in the cytoplasm. As thyroid hormone plays a pivotal role on metabolic homeostasis, CRYM may have influence on cellular metabolic processes. Loss of CRYM caused obesity in high fat diet (HFD) with glucose intolerance, fatty liver and hypertrophy of epididymal adipocyte, we have previously reported (BBRC 2019;508:914-920). Although the previous study has shown that the amount of HFD which CRYM knock out (KO) mice ate was larger than the one wild type (WT) mice did, the precise metabolic mechanisms has not been determined. In this study, we assessed the metabolic effects of CRYM expression by pair-feeding. We have found that the ratio of adipose tissue to body weight in CRYM KO mice significantly increases compared to those of WT mice (WT 0.034±0.009, CRYM KO 0.044±0.008 (mean±SD), p=0.04) in the pair-feeding test. However, there were no significant difference of body weights between two groups (WT 31.8±2.0g, CRYM KO 31.3±1.5g(mean±SD)). The microarray examination using visceral adipocytes of HFD fed mice showed that the several genes related to lipid metabolisms up-regulated in CRYM KO mice. Among them, the gene expression of the WNT1 inducible signaling pathway protein 2, inhibiting adipose differentiation, was significantly up-regulated in pair-feeding HFD CRYM KO mice (Z-score 2.18). In addition, the Lrp4, fzd10 and wnt10a genes, as adipogenesis inhibitors through a β-catenin-dependent mechanism, elevated in free feeding HFD CRYM KO mice. Collectively, our data suggests that lack of CRYM causes visceral adipose tissue hypertrophy not only because of appetite, but also maybe because of inhibitory effects on adipocyte differentiation in a caloric excess environment. Disclosure: Y. Ohkubo: None. S. Nishio: None. Y. Shimada: None. S. Kubota: None. J. Kitahara: None. Y. Shibata: None. K. Kitajima: None. T. Sekido: None. S. Suzuki: None. M. Komatsu: None.
- Publication
Diabetes, 2020, Vol 69, pN.PAG
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db20-1935-P