Obesity suppresses cellular process critical to kidney health

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.”

Highlights

Unlike 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.

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