Maine Medical Center, Medical Education, Maine Medical Center Research Institute
Obesity, Adipose Tissue, Diet, Signal Transduction
Background: Obesity is an established risk factor for cardiovascular diseases (CVD) and possibly shares molecular and cellular disease mechanisms as CVD due to their comorbidity. As a component of vasculature, perivascular adipose tissue (PVAT) has been recognized as a critical regulator of vascular function due to its anatomical proximity to the vascular wall. Study in PVAT thus help us understand cross talks between adipose tissue and cardiovascular system to re-evaluate clinical strategies for prevention and treatment of type 2 diabetes and CVD. Recent studies have shown that in addition to development, Notch/Rbp-jk signaling plays a crucial role in regulating metabolic homeostasis. Knockout of Notch signaling components was reported to induce beige phenotypes of white adipose tissue (Bi et al., 2014). Methods: We studied how Notch/Rbp-jk signaling and potential downstream pathways regulate health of PVAT using in vitro model and in vivo conditional knockout mice. PVAT derived stromal vascular fractions were differentiated into adipocytes and gene expression of Notch signaling component was further assessed. We also generated mouse models with adipose tissue specific knockout of Rbpj genes using Adipoq-Cre driver and examined their physiology, histology, and expression of metabolic and vascular relaxation pathway components as compared to control non-Cre mice. Results: Our data showed that Notch signaling was activated in PVAT during high fat diet (HFD) treatment. We found expression of Notch signaling component including RBPJ-k was increased during differentiation process of PVAT. We also found that knockout of Notch signaling in PVAT reduces obese phenotype of PVAT including adipocyte hypertrophy during HFD treatment. Moreover, PVAT of RBPJ conditional knock-out mice showed altered gene expression in the vasorelaxation pathway including eNOS signaling; and this potentially works through PI3/AKT pathways. Conclusion: Notch signaling plays important roles in regulating metabolic homeostasis of adipose tissue including PVAT. In addition, Notch signaling could potentially regulates PVATmediated vasorelaxation through energy metabolism pathways
Yang, Chenhao; Boucher, Joshua M.; Ryzhova, Larisa M.; and Liaw, Lucy, "Notch signaling regulates perivascular adipose tissue (PVAT) function during diet-induced obesity" (2020). Costas T. Lambrew Research Retreat 2020. 30.