AMPK mediates the initiation of kidney disease induced by a high-fat diet

Anne Emilie Declèves, Anna V. Mathew, Robyn Cunard, Kumar Sharma

Research output: Contribution to journalArticle

120 Citations (Scopus)

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 2O 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 2O 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.

Original languageEnglish (US)
Pages (from-to)1846-1855
Number of pages10
JournalJournal of the American Society of Nephrology
Volume22
Issue number10
DOIs
StatePublished - Oct 1 2011
Externally publishedYes

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AMP-Activated Protein Kinases
Kidney Diseases
High Fat Diet
Kidney
Urine
Hypertrophy
Mesangial Cells
Palmitic Acid
Adiponectin
Inbred C57BL Mouse
Weight Gain
Fibrosis
Obesity
Body Weight
Inflammation

ASJC Scopus subject areas

  • Nephrology

Cite this

AMPK mediates the initiation of kidney disease induced by a high-fat diet. / Declèves, Anne Emilie; Mathew, Anna V.; Cunard, Robyn; Sharma, Kumar.

In: Journal of the American Society of Nephrology, Vol. 22, No. 10, 01.10.2011, p. 1846-1855.

Research output: Contribution to journalArticle

Declèves, Anne Emilie ; Mathew, Anna V. ; Cunard, Robyn ; Sharma, Kumar. / AMPK mediates the initiation of kidney disease induced by a high-fat diet. In: Journal of the American Society of Nephrology. 2011 ; Vol. 22, No. 10. pp. 1846-1855.
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