| First Author | Nahon JE | Year | 2019 |
| Journal | Biochim Biophys Acta Mol Basis Dis | Volume | 1865 |
| Issue | 2 | Pages | 494-501 |
| PubMed ID | 30448542 | Mgi Jnum | J:271296 |
| Mgi Id | MGI:6277880 | Doi | 10.1016/j.bbadis.2018.11.009 |
| Citation | Nahon JE, et al. (2019) Proteoglycan 4 deficiency protects against glucose intolerance and fatty liver disease in diet-induced obese mice. Biochim Biophys Acta Mol Basis Dis 1865(2):494-501 |
| abstractText | OBJECTIVE: Proteoglycan 4 (Prg4) has emerged from human association studies as a possible factor contributing to weight gain, dyslipidemia and insulin resistance. In the current study, we investigated the causal role of Prg4 in controlling lipid and glucose metabolism in mice. METHODS: Prg4 knockout (KO) mice and wild-type (WT) littermates were challenged with an obesogenic high-fat diet (45% of total calories as fat) for 16weeks. To further stimulate the development of metabolic alterations, 10% fructose water was provided starting from week 13. RESULTS: Prg4 deficiency only tended to reduce diet-induced body weight gain, but significantly improved glucose handling (AUC: -29%; p<0.05), which was also reflected by a tendency towards a reduced HOMA-IR score (-49%; p=0.06 as compared to WT mice). This coincided with lower hepatic expression of glycolysis (Gck: -30%; p<0.05) and lipogenesis (Acc: -21%; p<0.05 and Scd1: -38%; p<0.001) genes, which translated in significantly lower hepatic triglyceride levels (-56%; p<0.001) in Prg4 KO mice as compared to WT mice. Prg4 KO mice likely had lower glucose utilization by skeletal muscle as compared to WT mice, judged by a significant reduction in the genes Glut4 (-29%; p<0.01), Pfkm (-21%; p<0.05) and Hk2 (-39%; p<0.001). Moreover, Prg4 KO mice showed a favorable white adipose tissue phenotype with lower uptake of triglyceride-derived fatty acids (-46%; p<0.05) and lower gene expression of inflammatory markers Cd68, Mcp1 and Tnfalpha (-65%, -81% and -63%, respectively; p<0.01) than WT mice. CONCLUSION: Prg4 KO mice are protected from high-fat diet-induced glucose intolerance and fatty liver disease. |
