Regulation of lipid accumulation by AMK-activated kinase in high fat
diet-induced kidney injury.
Authors Declèves AE, Zolkipli Z, Satriano J, Wang L, Nakayama T, Rogac M, Le TP, Nortier
JL, Farquhar MG, Naviaux RK, Sharma K
Submitted By Kumar Sharma on 4/15/2014
Status Published
Journal Kidney international
Year 2014
Date Published 3/1/2014
Volume : Pages 85 : 611 - 623
PubMed Reference 24304883
Abstract AMP-activated protein kinase (AMPK) is an important energy sensor that may be
critical in regulating renal lipid accumulation. To evaluate the role of AMPK in
mediating renal lipid accumulation, C57BL/6J mice were randomized to a standard
diet, a high-fat diet, or a high-fat diet plus AICAR (an AMPK activator) for 14
weeks. Renal functional and structural studies along with electron microscopy
were performed. Mice given the high-fat diet had proximal tubule injury with the
presence of enlarged clear vacuoles, and multilaminar inclusions concurrent with
an increase of tissue lipid and overloading of the lysosomal system. The margins
of the clear vacuoles were positive for the endolysosomal marker, LAMP1,
suggesting lysosome accumulation. Characterization of vesicles by special stains
(Oil Red O, Nile Red, Luxol Fast Blue) and by electron microscopy showed they
contained onion skin-like accumulations consistent with phospholipids. Moreover,
cholesteryl esters and phosphatidylcholine-containing phospholipids were
significantly increased in the kidneys of mice on a high-fat diet. AMPK
activation with chronic AICAR treatment prevented the clinical and structural
effects of high-fat diet. Thus, high-fat diet contributes to a dysfunction of
the lysosomal system and altered lipid metabolism characterized by cholesterol
and phospholipid accumulation in the kidney. AMPK activation normalizes the
changes in renal lipid content despite chronic exposure to lipid challenge.

Investigators with authorship
Kumar SharmaUniversity of California San Diego