| First Author | Yang J | Year | 2021 |
| Journal | Metabolism | Volume | 120 |
| Pages | 154777 | PubMed ID | 33865898 |
| Mgi Jnum | J:310396 | Mgi Id | MGI:6750981 |
| Doi | 10.1016/j.metabol.2021.154777 | Citation | Yang J, et al. (2021) Collagen beta(1-O) galactosyltransferase 2 deficiency contributes to lipodystrophy and aggravates NAFLD related to HMW adiponectin in mice. Metabolism 120:154777 |
| abstractText | AIM: Our previous results showed that Colgalt1 knock-out resulted in fetal death on day E11.5, and collagen secretion was retarded. This study aimed to elucidate the role of Collagen beta(1-O) galactosyltransferase 2 (Colgalt2) in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). METHODS: Colgalt2(-/-) mice were fed a high-fat diet (HFD) or methionine-and choline-deficient diet (MCD). Nanopore long-read RNA-Seq analysis of liver tissues was used to profile genomic variation. In vitro, hepatocyte steatosis and differentiation of primary pre-adipocytes were induced. RESULTS: Colgalt2(-/-) mice exhibited lipodystrophy, increased body weight, and hepatic lipid accumulation at 6weeks of age. Colgalt2 deficiency aggravated hepatic steatosis in mice fed an HFD or a standard laboratory chow diet. Colgalt2 deficiency promotes steatohepatitis in MCD-fed mice. In HFD mice, Colgalt2 deficiency caused lipodystrophy and decreased plasma HMW, total adiponectin, and leptin levels. Colgalt2 deficiency also reduced circulating HMW/Total adiponectin in mice fed a HFD diet without differences of adiponectin mRNA and protein level in WT and Colgalt2(-/-) mice. The nanopore long-read RNA-Seq analysis results revealed transcriptional changes in the adiponectin receptor downstream signaling pathway and lipogenic genes, including the AMPK signaling pathway, adipocytokine signaling pathway, and lipid metabolism (Cidea, Cidec, CD36, and PPARgamma). Colgalt2 deficiency did not promote lipid accumulation in OA-induced HepG2 cells or primary hepatocytes. However, Colgalt2 deficiency inhibited adipogenesis and reduced PPARgamma, adipogenesis-related transcription factors, and expression during adipocyte differentiation. CONCLUSIONS: In mice, Colgalt2 deficiency contributes to lipodystrophy and promotes NAFLD related to HMW adiponectin. These results suggest that Colgalt2 could be a novel and promising therapeutic strategy for the treatment of NAFLD. |
