Adiponectin regulates albuminuria and podocyte function in mice.
Authors Kumar Sharma, M.D., Satish RamachandraRao, Ph.D., Gang Qiu, M.S., Hitomi Kataoka
Usui, M.D., Yanqing Zhu, M.D., Stephen R. Dunn, B.S., Raogo Ouedraogo, Ph.D.,
Kelly Hough, Peter McCue, M.D., Lawrence Chan, M.D., Bonita Falkner, M.D., Barry
J. Goldstein, M.D., Ph.D.
Submitted By Kumar Sharma on 2/5/2008
Status Published
Journal The Journal of clinical investigation
Year 2008
Date Published 5/1/2008
Volume : Pages 118 : 1645 - 1656
PubMed Reference 18431508
Abstract Increased albuminuria is associated with obesity and diabetes and is an
important risk factor for cardiovascular and renal disease. However, the link
between early albuminuria and adiposity is unclear. To demonstrate whether
adiponectin, an adipocyte-derived hormone, is a communication signal between
adipocytes and the kidney, studies were performed in a cohort of patients at
high risk for diabetes and kidney disease (obese African Americans (AA)), as
well as in adiponectin knockout (Ad-/-) mice and podocytes in culture.
Albuminuria had a negative correlation with plasma adiponectin in obese AA
subjects. Ad-/- mice exhibited increased albuminuria and podocyte foot process
fusion. In cultured podocytes, adiponectin and 5’AMP-activated protein kinase
(AMPK) reduced permeability to albumin and ZO-1 translocation to cytosol. The
beneficial effect of adiponectin and AMPK appeared to be contributed by
reduction of oxidant stress as adiponectin and AICAR reduced protein levels of
NADPH oxidase Nox4 in podocytes. Ad-/- mice with and without diabetes had
normalization of albuminuria with adiponectin treatment. Ad -/- mice treated
with adiponectin also demonstrated improvement of foot process effacement,
increased glomerular AMPK activation and reduced urinary and glomerular markers
of oxidant stress. We conclude that adiponectin is a key signal regulating
albuminuria, likely via modulating AMPK and Nox4 in podocytes.

Investigators with authorship
Kumar SharmaUniversity of California San Diego


Adipoqadiponectin, C1Q and collagen domain containing