For Immediate Release
December 24th, 2020

New link between cholesterol and hyperuricemia offers potential astherapeutic target
A new link between a high cholesterol condition and an excess blood uric acidlevel has been identified by an international collaboration among Nara Medical University,
RIKEN, and the University of Houston. A cholesterol metabolite, known as 27HC (27hydroxycholesterol), was found to increase the expression of uric acid transporter thatfacilitates reabsorption, and may prove to be a promising drug target (Figure 1).
The new study, conducted by a team of researchers from Nara MedicalUniversity led by senior author Dr. Eiichiro Mori, Associate Professor and chair of theDepartment of Future Basic Medicine, University of Houston led by co-senior author Dr.
Michihisa Umetani, Assistant Professor of the Center for Nuclear Receptors and Cell
Signaling, and RIKEN Center for Biosystems Dynamics Research led by Dr. Minoru
Takasato, Team Leader of Laboratory for Human Organogenesis, was recently publishedin The FASEB Journal.
Elevated levels of blood uric acid, or hyperuricemia, lead to various diseases
such as gout, renal diseases, and cardiovascular diseases. Most uric acid is excreted in theurine, while some portion of uric acid is reabsorbed from urine to blood to maintain aproper level of blood uric acid through uric acid reabsorption transporters. The correlation
between hyperuricemia and metabolic diseases, such as obesity and high cholesterolconditions, is well known. However, the mechanisms driving the impact of cholesterol onuric acid transporters were unknown.
Using human cells, animal models, and human kidney organoids generated frominduced pluripotent stem (iPS) cells, the researchers found that 27HC promotes theexpression of URAT1 (also known as SLC22A12), which plays an important role in thereabsorption process, via estrogen receptors in the kidney (Figure 2). Their results
indicate that elevated levels of 27HC in a high cholesterol condition can increase uric acidreabsorption, which in turn increases blood uric acid levels. These findings shed new lighton a novel treatment option for hyperuricemia-related diseases by targeting 27HC.

Figure 1. The effects of 27-hydroxycholesterol in various tissues discovered by this group.

Figure 2. 27HC binds to estrogen receptors (ER) and induces URAT1/SLC22A12expression.

Published Paper: 27-Hydroxycholesterol regulates human SLC22A12 gene expression
through estrogen receptor action
Authors: Masaya Matsubayashi, Yoshihiko M Sakaguchi, Yoshiki Sahara, Hitoki Nanaura,
Sotaro Kikuchi, Arvand Asghari, Linh Bui, Shinko Kobashigawa, Mari
Nakanishi, Riko Nagata, Takeshi K Matsui, Genro Kashino, Masatoshi
Hasegawa, Shin Takasawa, Masahiro Eriguchi, Kazuhiko Tsuruya, Shushi
Nagamori, Kazuma Sugie, Takahiko Nakagawa, Minoru Takasato, Michihisa
Umetani, Eiichiro Mori
Published Journal: The FASEB Journal
doi: 10.1096/fj.202002077R
Contact
Nara Medical University
Department of Future Basic Medicine
Associate Professor and Chair
Eiichiro Mori, M.D., Ph.D.
emori@naramed-u.ac.jp【For Inquiry regarding Media Coverage】
Nara Medical University Research Support Division
Person in Charge: Sakata, Takesue
Tel: +81-744-22-3051(ex: 2552)
RIKEN
Jens Wilkinson, Communications Officer
Mail: pr@riken.jp