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Reducing endocannabinoid system’s activity may help protect the kidney health of individuals with obesity

07/09/2017

New study provides insight on the mechanisms behind the development of kidney damage due to obesity, points to a potential target for protecting the kidney health of individuals with obesity

Highlights: Structural and functional changes in the kidneys develop early in the course of obesity. A particular receptor in kidney cells plays an important role in obesity-induced fat accumulation, dysfunction, injury, inflammation, and scarring in the kidney. The receptor acts through a certain signaling pathway. Targeting this receptor or the signaling pathway may help protect the kidneys of individuals who develop obesity.

Jerusalem, September 6, 2017 — A new study provides insights on the mechanisms behind the development of kidney damage due to obesity. The findings, which appear in an upcoming issue of the Journal of the American Society of Nephrology (JASN), point to a potential target for protecting the kidney health of individuals with obesity.

Obesity-related kidney dysfunction develops early in the course of obesity, justifying the search for novel regulators that could be targeted for therapy. Obesity can cause structural and functional changes in the kidneys, which may help explain why individuals with obesity face an elevated risk of chronic kidney disease and its progression to kidney failure. Although multiple metabolic factors have been proposed to contribute to obesity-induced kidney problems, the underlying mechanisms are not completely understood.

To investigate, a team led by Dr. Joseph (Yossi) Tam, DMD, PhD and the PhD student Shiran Udi, MSc, at the Hebrew University of Jerusalem’s Institute for Drug Research in Israel, examined the kidney cells that are responsible for the reabsorption of nutrients, while allowing other substances of no nutritional value to be excreted in the urine. These kidney cells, called renal proximal tubular cells or RPTCs, are especially sensitive to the accumulation of fat, or lipids — an effect called lipotoxicity.

The researchers examined the potential role of endocannabinoids, lipid molecules that interact with the cannabinoid-1 receptor (CB1R) and are abundantly expressed in the brain and periphery, including the kidney. Endocannabinoids act on the CB1R receptor in RPTC renal cell lipotoxicity. Mice that lacked expression of the receptor in the RPTC renal cells experienced significantly less obesity-induced lipid accumulation in the kidney as well as less kidney dysfunction, injury, inflammation, and scarring.

Moreover, the study revealed the molecular signaling pathway involved in mediating the kidney injury and lipotoxicity in RPTC renal cells induced by the CB1R cellular receptors. Specifically, these deleterious effects associated with decreased activation of liver kinase B1 and the energy sensor AMP-activated protein kinase, as well as reduced fatty acid β-oxidation.

The research shows that manipulating the cannabinoid-1 receptor (CB1R) specifically in the RPTC renal cells may provide a novel therapeutic intervention for treating obesity-induced nephropathy.

“This work provides a novel approach to slow the development of renal injury through chronic blockade of peripheral CB1Rs,” said Dr. Tam. “It also supports strategies aimed at reducing the activity of the endocannabinoid system, specifically in the kidney, to attenuate the development of RPTC dysfunction in obesity.”

Study co-authors include Liad Hinden, PhD, Brian Earley, MSc, Adi Drori, PhD, Noa Reuveni, Rivka Hadar, MSc, Resat Cinar, PhD, and Alina Nemirovski, PhD.  Dr. Tam is Director of the Hebrew University’s Multidisciplinary Center on Cannabinoid Research (http://cannabinoids.huji.ac.il), and Head of the Obesity and Metabolism Laboratory at the Hebrew University’s Institute for Drug Research in the Faculty of Medicine.

FUNDING: The work was supported by a German-Israeli Foundation grant (#I-2345-201.2/2014), and an ERC-2015-StG grant (#676841) to Dr. Joseph Tam.

CITATION: Shiran Udi, Liad Hinden et al. Proximal Tubular Cannabinoid-1 Receptor Regulates Obesity-Induced CKD. Published online before print August 31, 2017. Journal of the American Society of Nephrology (JASN), doi: 10.1681/ASN.2016101085, http://jasn.asnjournals.org/content/early/2017/08/30/ASN.2016101085

Reducing endocannabinoid system’s activity may help protect the kidney health of individuals with obesity
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Hebrew University and City of Jerusalem to Host 'International Conference on the Cannabinoids' in 2021

26/07/2017
From 'Startup Nation' to 'Cannabis Research Nation'

The International Cannabinoid Research Society (ICRS - http://icrs.co) has chosen the Hebrew University of Jerusalem to host the International Symposium on the Cannabinoids in 2021 in Jerusalem.

The ICRS is the oldest scientific society dedicated to the research in the cannabis plant, cannabinoids, and their physiological and biochemical targets.  The ICRS has nearly 400 members from all over the world.  The members and guests of the ICRS gather yearly to present the ICRS Symposium.

Hundreds of participants from Israel and around the world will participate in the conference, at the International Convention Center (ICC) in Jerusalem, in cooperation with the Jerusalem Conventions & Visitors Bureau (JCVB), which operates under the Jerusalem Development Authority (JDA).

The event will be hosted by the Hebrew University's Multidisciplinary Center on Cannabinoid Research (MCCR - http://cannabinoids.huji.ac.il), which is the leading center in Israel for conducting and coordinating research on cannabinoids, endocannabinoids and medical Cannabis.

Over the last 50 years, Hebrew University research has spearheaded a new scientific era of Cannabis research. Prof. Raphael Mechoulam, a Hebrew University researcher widely regarded as “the father of cannabinoid research,” and his colleagues isolated the active constituent of the Cannabis plant, tetrahydrocannabinol, elucidated its structure, and synthesized it. Later Prof. Mechoulam identified the endogenous cannabinoids (formed in the mammalian body) and thus pioneered the field of cannabinoid research.

The International Symposium will mark Prof. Mechoulam’s 90th birthday in his home town of Jerusalem.

The Symposium will feature oral and poster presentations covering a wide range of topics germane to cannabinoid science and medicine. Past conferences have covered such topics as autoimmunity, epilepsy, pain, PTSD, drug development and medicinal chemistry, neuroprotection, metabolism, endocrine and obesity, cancer, and much more.

Prof. Cecilia Hillard, Executive Director of the ICRS, said: "The board of directors of the International Cannabinoid Research Society is very pleased that our 31st annual meeting will be held in Jerusalem in 2021.  Jerusalem holds a special place in the history of the science of cannabis and the endocannabinoids. Prof. Raphael Mechoulam of Hebrew University was the first to publish the structure of the active principal of cannabis, THC and was also the first to identify an endogenous cannabinoid, anandamide.  Just as impressive is the current state of cannabinoid research in Jerusalem and Israel at large, including the Multidisciplinary Center on Cannabinoid Research led by Dr. Tam.  We are looking forward to visiting Jerusalem and to an exciting and informative conference."

Dr. Joseph (Yossi) Tam, Director of the Hebrew University’s Multidisciplinary Center on Cannabinoid Research, said: "I’m excited that the International Cannabinoid Research Society has decided hold its 31st conference in Jerusalem under the auspices of the Multidisciplinary Center on Cannabinoid Research. One of our first goals after establishing the Center was to host the ICRS conference in Jerusalem, so that the international community of researchers can learn about the highly advanced work in the field of cannabinoids carried out in the Center and in Israel. I am certain that hosting this high-level conference will constitute another turning point in Israel's position as a global leader in cannabinoid research and development.”

"Modulating endocannabinoid activity has therapeutic potential in a large number of human diseases, and research on cannabinoids may lead to very significant advances in basic science and therapeutics. We look forward to hosting the world’s top scientists working to discover new therapies based on cannabinoids,” said Prof. Raphael Mechoulam, Head of the Academic Committee of the Multidisciplinary Center, and the Lionel Jacobson Professor Emeritus of Medicinal Chemistry in the Hebrew University’s Faculty of Medicine.

"Bringing this global symposium to Jerusalem emphasizes the ongoing collaboration between multiple institutions including the JCVB, ICC, and MCCR. This partnership was only possible with the shared vision in highlighting the city’s potential as a leading scientific conference destination. Jerusalem offers an ideal setting to host the over 400 global researchers to learn and promote the exchange of scientific information and gain new perspectives about Cannabis," said Ilanit Melchior, Director of Tourism in Jerusalem.

“As the largest and leading conference center in Israel, the Jerusalem ICC looks forward to hosting this important conference aimed at bringing international researchers together to improve human health and well-being,” said Mira Altman, CEO of the International Convention Center (ICC) in Jerusalem.

The ICRS is a scientific association with hundreds of international members, all active researchers in the field of endogenous, plant-derived and synthetic cannabinoids and related bioactive lipids. The ICRS Symposium is considered the most important conference in the field of cannabinoids research. The conference brings together the leading researchers from the international scientific community and presents the latest and most up-to-date research in the field.

The Multidisciplinary Center on Cannabinoid Research, staffed by leading scientists and medical doctors from the Hebrew University and its affiliated Hadassah Medical Center, conducts and coordinates exciting new research about cannabinoids, endocannabinoids and medical Cannabis, while promoting collaboration and disseminating information. More info at http://cannabinoids.huji.ac.il/.

The Hebrew University of Jerusalem, Israel’s leading academic and research institution, is ranked among the top 100 universities in the world. Founded in 1918 by visionaries including Albert Einstein, the Hebrew University is a pluralistic institution where science and knowledge are advanced for the benefit of humankind. For more information, please visit http://new.huji.ac.il/en

Image for download: Hebrew University’s Multidisciplinary Center on Cannabinoid Research (Credit: Hebrew University) http://media.huji.ac.il/new/photos/hu170405_MDCR.jpg

Hebrew University and City of Jerusalem to Host 'International Conference on the Cannabinoids' in 2021
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