ADAR2 deficiency ameliorates non-alcoholic fatty liver disease and muscle atrophy through modulating serum amyloid A1

Authors
Mei-Lang Kung, Tai-Hua Yang, Chia-Chi Lin, Jia-Yun Ho, Tzu-Chi Hung, Chih-Hsiang Chang, Kuan-Wen Huang, Chien-Chin Chen, Yun-Wen Chen


Lab

Journal
Journal of Cachexia, Sarcopenia and Muscle

Abstract
As obesity impacts glucose metabolism and insulin action, we next analysed the capacity of the mice to break down glucose by performing a glucose tolerance test (GTT) on mice fed with ND or HFD for 20weeks. After 20weeks of HFD feeding, male ADAR2 KO mice displayed improvements in glucose tolerance (Figure2) when compared with WT mice, but both female WT and female ADAR2 showed a similar pattern of glucose intolerance after 20weeks of HFD feeding (FigureS4A). We then tested the insulin sensitivity of ADAR2 KO mice by performing an insulin tolerance test (ITT). We found that male ADAR2 KO mice increased insulin sensitivity under HFD (Figure2). In contrast, ADAR2 KO did not enhance insulin sensitivity in female mice fed with HFD (FigureS4B). Moreover, HFD led to upregulated fasting plasma glucose levels in WT mice and ADAR2 KO mice compared with the ND control, but ADAR2 KO did not lower fasting plasma glucose levels in female WT mice fed with HFD (FigureS4C). Hence, we focused on males for the rest of the studies. Our plasma biochemical examinations showed elevated levels of plasma glucose, insulin (Figure2), total cholesterol, free fatty acid and TGs in the HFD obese mice (Figure2). ADAR2 KO attenuated these metabolic dysregulations (Figure2). Furthermore, the homeostasis model assessment-estimated insulin resistance (HOMA-IR) index was calculated to evaluate systemic IR. Compared with the ND group, the HOMA-IR value was significantly increased with HFD feeding, whereas the HOMA-IR value had a lower induction upon the HFD diet in ADAR2 KO mice (Figure2). The HOMA-Beta index was calculated to evaluate beta-cell function. Compared with the ND group, the HOMA-Beta value was significantly increased with HFD feeding, whereas ADAR2 silencing completely abolished the HFD-induced effect in ADAR2 KO mice (Figure2).

Keywords/Topics
deficiency;ameliorates;non-alcoholic;fatty;liver;disease;muscle;atrophy;through;modulating

BIOSEB Instruments Used:
Grip strength test (BIO-GS4)

Source :

https://onlinelibrary.wiley.com/doi/abs/10.1002/jcsm.13460

Produits associés

Test d'agrippement

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