期刊
DIABETES
卷 66, 期 6, 页码 1479-1490出版社
AMER DIABETES ASSOC
DOI: 10.2337/db16-1081
关键词
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资金
- National Institutes of Health [R01-DK55758, R01-DK099110, P01-DK088761]
- Cancer Prevention and Research Institute of Texas [CPRIT RP140412]
- Korea Health Technology R&D Project through the Korea Health Industry Development Institute - Ministry of Health & Welfare, Republic of Korea [HI14C1277]
- Basic Science Research Program through the National Research Foundation of Korea - Ministry of Education [NRF-2014R1A1A2054914]
- Priority Research Centers Program through the National Research Foundation of Korea - Ministry of Education, Science and Technology [2010-0020224]
- pilot award from the Center for Clinical and Translational Sciences at The University of Texas Health Science Center at Houston [UL1-TR-000371]
Adipocyte-derived vascular endothelial growth factor-A (VEGF-A) plays a crucial role in angiogenesis and contributes to adipocyte function and systemic metabolism, such as insulin resistance, chronic inflammation, and beiging of subcutaneous adipose tissue. Using a doxycycline-inducible adipocyte-specific VEGF-A-overexpressing mouse model, we investigated the dynamics of local VEGF-A effects on tissue beiging of adipose tissue transplants. VEGF-A overexpression in adipocytes triggers angiogenesis. We also observed a rapid appearance of beige fat cells in subcutaneous white adipose tissue as early as 2 days postinduction of VEGF-A. In contrast to conventional cold-induced beiging, VEGF-A-induced beiging is independent of interleukin-4. We subjected metabolically healthy VEGF-A-overexpressing adipose tissue to autologous transplantation. Transfer of subcutaneous adipose tissues taken from VEGF-A-overexpressing mice into diet-induced obese mice resulted in systemic metabolic benefits, associated with improved survival of adipocytes and a concomitant reduced inflammatory response. These effects of VEGF-A are tissue autonomous, inducing white adipose tissue beiging and angiogenesis within the transplanted tissue. Our findings indicate that manipulation of adipocyte functions with a bona fide angiogenic factor, such as VEGF-A, significantly improves the survival and volume retention of fat grafts and can convey metabolically favorable properties on the recipient on the basis of beiging.
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