AMPK Mediates the Initiation of Kidney Disease Induced by a High-Fat Diet.
Authors Declèves AE, Mathew AV, Cunard R, Sharma K
Submitted By Kumar Sharma on 1/12/2011
Status Published
Journal Journal of the American Society of Nephrology : JASN
Year 2011
Date Published 10/1/2011
Volume : Pages Not Specified : Not Specified
PubMed Reference 21921143
Abstract The mechanisms underlying the association between obesity and progressive renal
disease are not well understood. Exposure to a high-fat diet decreases levels of
the cellular energy sensor AMPK in many organs, including the kidney, but
whether AMPK contributes to the pathophysiology of kidney disease induced by a
high-fat diet is unknown. In this study, we randomly assigned C57BL/6J mice to a
standard or high-fat diet. After 1 week, mice fed a high-fat diet exhibited an
increase in body weight, renal hypertrophy, an increase in urine H(2)O(2) and
urine MCP-1, and a decrease in circulating adiponectin levels and renal AMPK
activity. Urine ACR progressively increased after 4 weeks of a high-fat diet.
After 12 weeks, kidneys of mice fed a high-fat diet demonstrated a marked
increase in markers of fibrosis and inflammation, and AMPK activity remained
significantly suppressed. To determine whether inhibition of AMPK activity
explained these renal effects, we administered an AMPK activator along with a
high-fat diet for 1 week. Although AMPK activation did not abrogate the weight
gain, it reduced the renal hypertrophy, urine H(2)O(2), and urine and renal
MCP-1. In vitro, AMPK activation completely inhibited the induction of MCP-1 by
palmitic acid in mesangial cells. In conclusion, these data suggest that the
energy sensor AMPK mediates the early renal effects of a high-fat diet.

Investigators with authorship
Kumar SharmaUniversity of California San Diego