Other
12 Authors
- Mohabeer A,
- Caruso LL,
- Giacca A,
- Fu F,
- Schroer SA,
- Lino M,
- Bendeck MP,
- Harper C,
- Liu A,
- Woo M,
- McKee T,
- Ngai D
| First Author | Lino M | Year | 2020 |
| Journal | Mol Metab | Volume | 39 |
| Pages | 101006 | PubMed ID | 32360427 |
| Mgi Jnum | J:330761 | Mgi Id | MGI:6714689 |
| Doi | 10.1016/j.molmet.2020.101006 | Citation | Lino M, et al. (2020) Discoidin domain receptor 1-deletion ameliorates fibrosis and promotes adipose tissue beiging, brown fat activity, and increased metabolic rate in a mouse model of cardiometabolic disease. Mol Metab 39:101006 |
| abstractText | OBJECTIVE: Discoidin domain receptor 1 (DDR1) is a collagen binding receptor tyrosine kinase implicated in atherosclerosis, fibrosis, and cancer. Our previous research showed that DDR1 could regulate smooth muscle cell trans-differentiation, fibrosis and calcification in the vascular system in cardiometabolic disease. This spectrum of activity led us to question whether DDR1 might also regulate adipose tissue fibrosis and remodeling. METHODS: We have used a diet-induced mouse model of cardiometabolic disease to determine whether DDR1 deletion impacts upon adipose tissue remodeling and metabolic dysfunction. Mice were fed a high fat diet (HFD) for 12 weeks, followed by assessment of glucose and insulin tolerance, respiration via indirect calorimetry, and brown fat activity by FDG-PET. RESULTS: Feeding HFD induced DDR1 expression in white adipose tissue, which correlated with adipose tissue expansion and fibrosis. Ddr1(-/-) mice fed an HFD had improved glucose tolerance, reduced body fat, and increased brown fat activity and energy expenditure compared to Ddr1(+/+) littermate controls. HFD-fed DDR1(-/-) mice also had reduced fibrosis, smaller adipocytes with multilocular lipid droplets, and increased UCP-1 expression characteristic of beige fat formation in subcutaneous adipose tissue. In vitro, studying C3H10T1/2 cells stimulated to differentiate, DDR1 inhibition caused a shift from white to beige adipocyte differentiation, whereas DDR1 expression was increased with TGFbeta-mediated pro-fibrotic differentiation. CONCLUSION: This study is the first to identify a role for DDR1 as a driver of adipose tissue fibrosis and suppressor of beneficial beige fat formation. |
