Obesity increases a chronic kidney disease patient's risk of developing kidney failure.
Obesity suppresses an important cellular process that prevents kidney cell damage, according to a study appearing in an upcoming issue of the Journal of the American Society of Nephrology (JASN). The findings suggest that restoring the process could protect the kidney health of obese individuals.
Obesity increases a chronic kidney disease patient's risk of developing kidney failure, but the mechanism underlying this connection has remained unclear.
Kosuke Yamahara, Takashi Uzu, MD, PhD (Shiga University of Medical Science, in Japan), and their colleagues suspected that decreased functioning of a process called autophagy might play a role. Autophagy is a degradation system within cells that removes damaged proteins and other defective cellular components, and autophagy insufficiency is common in obese individuals.
The researchers found that in normal-weight mice with kidney disease, autophagy was active in kidney cells. However, in obese mice with kidney disease, autophagy was suppressed and kidney cells became damaged. Normal-weight mice with kidney disease and defective autophagy (due to a gene deletion) also experienced kidney cell damage.
The investigators also discovered that a potent suppressor of autophagy (called mTOR) was hyperactivated in the kidneys of obese mice, and treatment with an mTOR inhibitor ameliorated autophagy insufficiency. Furthermore, both mTOR hyperactivation and autophagy suppression were observed in kidney specimens from obese patients with kidney disease.
"Obesity suppresses autophagy via an abnormal activation of nutrition sensing signals in the kidney," said Yamahara. "Our results suggest that restoring the kidney-protective action of autophagy may improve the kidney health of obese patients."
In an accompanying editorial, Ken Inoki, PhD (University of Michigan) stated that "the results of this study provide an important pathomechanism underlying obesity-associated renal… cell damage."
HighlightsUnlike in normal-weight mice with kidney disease, a degradation process called autophagy is suppressed in obese mice with kidney disease. This suppression leads to kidney cell damage.
Obese kidney disease patients also have suppressed autophagy.
Study co-authors include Shinji Kume, Daisuke Koya, Yuki Tanaka, Yoshikata Morita, Masami Chin-Kanasaki, Hisazumi Araki, Keiji Isshiki, Shin-ichi Araki, Masakazu Haneda, Taiji Matsusaka, Atsunori Kashiwagi, and Hiroshi Maegawa.
Disclosures: The authors reported no financial disclosures.
The article, entitled "Obesity-mediated Autophagy Insufficiency Exacerbates Proteinuria-induced Tubulointerstitial Lesions," will appear online at http://jasn.asnjournals.org/ on October 3, 2013, doi: 10.1681/ASN.2012111080.
The editorial, entitled "Proximal Tubules Forget 'Self-Eating' When They Meet Western Meals," will appear online at http://jasn.asnjournals.org/ on October 3, 2013, doi: 10.1681/ASN.2013070794.
The content of this article does not reflect the views or opinions of The American Society of Nephrology (ASN). Responsibility for the information and views expressed therein lies entirely with the author(s). ASN does not offer medical advice. All content in ASN publications is for informational purposes only, and is not intended to cover all possible uses, directions, precautions, drug interactions, or adverse effects. This content should not be used during a medical emergency or for the diagnosis or treatment of any medical condition. Please consult your doctor or other qualified health care provider if you have any questions about a medical condition, or before taking any drug, changing your diet or commencing or discontinuing any course of treatment. Do not ignore or delay obtaining professional medical advice because of information accessed through ASN. Call 911 or your doctor for all medical emergencies.
Founded in 1966, and with more than 14,000 members, the American Society of Nephrology (ASN) leads the fight against kidney disease by educating health professionals, sharing new knowledge, advancing research, and advocating the highest quality care for patients.
Tracy Hampton | EurekAlert!
New antibody analysis accelerates rational vaccine design
09.08.2018 | Scripps Research Institute
Distrust of power influences choice of medical procedures
01.08.2018 | Johannes Gutenberg-Universität Mainz
Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.
Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....
Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.
Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...
Scientists have discovered that the electrical resistance of a copper-oxide compound depends on the magnetic field in a very unusual way -- a finding that could help direct the search for materials that can perfectly conduct electricity at room temperatur
What happens when really powerful magnets--capable of producing magnetic fields nearly two million times stronger than Earth's--are applied to materials that...
The quality of materials often depends on the manufacturing process. In casting and welding, for example, the rate at which melts solidify and the resulting microstructure of the alloy is important. With metallic foams as well, it depends on exactly how the foaming process takes place. To understand these processes fully requires fast sensing capability. The fastest 3D tomographic images to date have now been achieved at the BESSY II X-ray source operated by the Helmholtz-Zentrum Berlin.
Dr. Francisco Garcia-Moreno and his team have designed a turntable that rotates ultra-stably about its axis at a constant rotational speed. This really depends...
If certain signaling cascades are misregulated, diseases like cancer, obesity and diabetes may occur. A mechanism recently discovered by scientists at the Leibniz- Forschungsinstitut für Molekulare Pharmakologie (FMP) in Berlin and at the University of Geneva has a crucial influence on such signaling cascades and may be an important key for the future development of therapies against these diseases. The results of the study have just been published in the prestigious scientific journal 'Molecular Cell'.
Cell growth and cell differentiation as well as the release and efficacy of hormones such as insulin depend on the presence of lipids. Lipids are small...
08.08.2018 | Event News
27.07.2018 | Event News
25.07.2018 | Event News
13.08.2018 | Physics and Astronomy
13.08.2018 | Physics and Astronomy
13.08.2018 | Physics and Astronomy