Fat-cell hormone associated with higher risk of kidney disease

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Washington, Apr 23 : A new study, led by an Indian-origin scientist, has found that low levels of a hormone, called adiponectin, which leads to development of insulin resistance, may be linked to a higher risk of kidney disease as well.

Kumar Sharma, M.D., F.A.H.A., professor of medicine and Director of Translational Research in Kidney Disease at UC San Diego's School of Medicine, in collaboration with Barry J. Goldstein from Thomas Jefferson University, conducted the study.

The results of this study show that adiponectin, produced by fat cells, circulates in the blood and acts to both suppress inflammation, known to be a contributor to diabetes and cardiovascular disease, and to reduce protein in the urine.

"A deficiency in adiponectin could be the major reason why obese patients develop the initial signs of kidney disease. At present, the connections between the kidney and the cardiovascular system are not clear. A better understanding of the relationships between the kidney, the cardiovascular system and obesity will be of major benefit in treating these common public health problems at an early stage," said Sharma.

He also said that increased level of protein in the urine, termed albuminuria, is linked with obesity. Albuminuria is an indicator of kidney disease and an important risk factor for cardiovascular disease.

"The findings in the kidney are consistent with beneficial effects we reported for adiponectin in the microvasculature, in which it reduces oxidative stress and inflammatory responses. In this setting, adiponectin suppresses the adverse effects of high glucose, which implies that it may eventually be shown to serve a protective role in patients with diabetes as well as those with obesity," said Goldstein.

In the kidney, a network of fine capillaries acts as a filter to prevent proteins in the blood from being secreted into the urine. This filter is made up of three components, one of which, the podocyte cell, regulates albuminuria.

"We discovered that the hormone adiponectin, produced by fat cells, is directly linked to the healthy function of podocytes," said Sharma.

While studying obese patients without obvious diabetes or kidney disease, the research team found that when blood adiponectin levels were low, there was a direct correlation to elevated albumin protein levels in the urine.

Then the scientists studied a knockout model of a mouse lacking the adinopectin hormone, and discovered that these mice had high urine albumin levels. Treatment of the mice with adiponectin brought the albuminuria back to normal levels.

When they conducted a study on a receptor on the podocyte cell surface that is associated with a molecular signaling pathway, the AMP kinase enzyme (AMPK), it was shown that if AMPK is stimulated, either chemically or by introducing adiponectin, the filter works normally to keep albumin from leaking out of the blood and into the urine. But, when adiponectin is lacking, the resulting decrease in AMPK activity contributes to dysfunction of the filter. This made the researchers conclude that deficiency of adiponectin is indeed causative to albuminuria.

"We know there are certain medicines that stimulate the AMPK pathway, including adiponectin and a drug called Metformin, which is commonly given to patients with diabetes," said Sharma.

"This study suggests that using the hormone adiponectin, Metformin or other therapies could work to protect kidney function in patients who are obese, even before they have diabetes," he added.

In the end, the researchers looked at markers of inflammation in the kidney that may be regulated by adiponectin, and found that the podocyte also produces an inflammatory enzyme called NOX4 which is increased in the absence of the hormone.

"When you don't have the hormone there to suppress it, NOX4 enzyme is stimulated and can potentially contribute to the inflammation going on in the kidney and perhaps elsewhere in the body," said Sharma.

He added that replacing the hormone adiponectin in obese patients might work preventively to help the podocytes do their job, thus preventing kidney damage and inflammation.

The study is published in the Journal of Clinical Investigation.

ANI

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