Document Detail

AMPK mediates the initiation of kidney disease induced by a high-fat diet.
MedLine Citation:
PMID:  21921143     Owner:  NLM     Status:  MEDLINE    
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.
Anne-Emilie Declèves; Anna V Mathew; Robyn Cunard; Kumar Sharma
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2011-09-15
Journal Detail:
Title:  Journal of the American Society of Nephrology : JASN     Volume:  22     ISSN:  1533-3450     ISO Abbreviation:  J. Am. Soc. Nephrol.     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-10-03     Completed Date:  2011-11-21     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  9013836     Medline TA:  J Am Soc Nephrol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1846-55     Citation Subset:  IM    
Center for Renal Translational Medicine, Division of Nephrology-Hypertension, Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
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MeSH Terms
AMP-Activated Protein Kinases / metabolism*
Albuminuria / etiology
Biological Markers / urine
Chemokine CCL2 / metabolism
Diet, High-Fat / adverse effects
Dietary Fats / adverse effects*
Enzyme Activation
Hyperglycemia / etiology
Hypertrophy / etiology
Insulin Resistance
Kidney Diseases / etiology,  metabolism*,  pathology
Kidney Glomerulus / metabolism,  pathology
Mice, Inbred C57BL
Obesity / complications,  enzymology*
Grant Support
Reg. No./Substance:
0/Biological Markers; 0/Ccl2 protein, mouse; 0/Chemokine CCL2; 0/Dietary Fats; EC Protein Kinases

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