Abstract 486: Role Of Matrix Gla Protein In Vascular Regulation In Brown Adipose Tissue

Autor: Li Zhang, Xiuju Wu, Xinjiang Cai, Xiaojing Qiao, Yucheng Yao, Kristina I Bostrom
Rok vydání: 2022
Předmět:
Zdroj: Arteriosclerosis, Thrombosis, and Vascular Biology. 42
ISSN: 1524-4636
1079-5642
DOI: 10.1161/atvb.42.suppl_1.486
Popis: Obesity is a world-wide problem; an estimated 38% of the world population will be overweight and 20% will be obese by 2030. Brown adipose tissue (BAT) is a thermogenic tissue that plays an important role in energy expenditure and glucose uptake. It is also highly vascularized but the regulation of vascular formation in BAT is poorly understood. The bone morphogenetic proteins (BMPs) are essential in both brown adipogenesis and angiogenesis. BMP7 controls progenitor commitment to pre-adipocytes in BAT, and BMP4 is a known angiogenic factor that is essential for white and brown adipogenic differentiation. Matrix Gla protein (MGP) acts as an inhibitor of BMP4/7 and is highly expressed in pre-adipocytes. We hypothesize that modulation of MGP affects BAT vascularization and function. Our results show that mice with global Mgp gene deletion (Mgp-/-) mice have poorly functional BAT, with abnormal mitochondria and decreased expression of thermogenic lineage markers as determined by RNA Seq analysis and qPCR. In addition, the vasculature showed significant increases in the number of brown adipose endothelial cells (ECs) and expression of markers for both EC lineage and progenitor cells. Furthermore, targeted Mgp deletion in ECs or adipose cells as directed by Cdh5- or Adiponectin-Cre transgenes in Mgp-floxed mice also affected the vascular outgrowth in BAT. Together the results suggest that MGP is an essential regulator of vascular outgrowth in BAT, likely through its ability to inhibit BMPs. A better understanding of this kind of regulation may be helpful in strategies to limit metabolic dysfunction in obesity and diabetes.
Databáze: OpenAIRE
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