Endothelial SIRT-1 has a critical role in the maintenance of capillarization in brown adipose tissue
Ryo Furuuchi,
Ippei Shimizu,
Yohko Yoshida,
Goro Katsuumi,
Masayoshi Suda,
Yoshiaki Kubota,
Kenneth Walsh,
Tohru Minamino
Affiliations
Ryo Furuuchi
Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8431, Japan; Bourbon Corporation, Niigata 945-8611, Japan; Department of Advanced Senotherapeutics, Juntendo University Graduate School of Medicine, Tokyo 113-8431, Japan
Ippei Shimizu
Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8431, Japan; Corresponding author
Yohko Yoshida
Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8431, Japan; Department of Advanced Senotherapeutics, Juntendo University Graduate School of Medicine, Tokyo 113-8431, Japan
Goro Katsuumi
Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8431, Japan
Masayoshi Suda
Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8431, Japan
Yoshiaki Kubota
Department of Anatomy, Keio University School of Medicine, Tokyo 160-8582, Japan
Kenneth Walsh
Division of Cardiovascular Medicine, Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA 22908, USA
Tohru Minamino
Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8431, Japan; Japan Agency for Medical Research and Development-Core Research for Evolutionary Medical Science and Technology (AMED-CREST), Japan Agency for Medical Research and Development, Tokyo 100-0004, Japan; Corresponding author
Summary: Brown adipose tissue (BAT) has critical roles in thermogenesis and systemic metabolism. Capillary rarefaction was reported to develop in BAT with dietary obesity, and previous studies showed that suppression of vascular endothelial growth factor A (VEGF-A) reduced capillary density in BAT, promoting the functional decline of this organ. Capillarization is regulated through the balance between angiogenesis and vasculogenesis on the one hand and apoptosis of endothelial cells (ECs) on the other; however, the role of EC apoptosis in BAT remained to be explored. In studies testing the role of boysenberry polyphenols (BoyP) in BAT, we found that BoyP decreased EC apoptosis, enhanced capillarization in BAT, and ameliorated dietary BAT dysfunction, which was associated with the upregulation of nicotinamide adenine dinucleotide-dependent protein deacetylase sirtuin 1 (SIRT-1) in ECs. Our studies suggest that EC SIRT-1 would be one of the potential targets of BoyP that contributes to BAT capillarization and function.
