RGD Reference Report - Calorie restriction modulates renal expression of sterol regulatory element binding proteins, lipid accumulation, and age-related renal disease. - Rat Genome Database

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Calorie restriction modulates renal expression of sterol regulatory element binding proteins, lipid accumulation, and age-related renal disease.

Authors: Jiang, T  Liebman, SE  Lucia, MS  Phillips, CL  Levi, M 
Citation: Jiang T, etal., J Am Soc Nephrol. 2005 Aug;16(8):2385-94. Epub 2005 Jun 8.
RGD ID: 1625196
Pubmed: PMID:15944339   (View Abstract at PubMed)
DOI: DOI:10.1681/ASN.2004080701   (Journal Full-text)

Sterol regulatory element binding proteins (SREBP) are major regulators of fatty acid and cholesterol synthesis. This study found that age-related renal matrix deposition and proteinuria were associated with increased renal expression of SREBP-1 and SREBP-2 and increased renal accumulation of triglyceride and cholesterol. Because calorie restriction (CR) modulates age-related renal disease, it then was determined whether the effects of CR are mediated partially by modulation of renal lipid metabolism. Compared with ad libitum (AL)-fed 24-month-old (24 m) F344BN rats, CR resulted in significant decreases in extracellular matrix accumulation (periodic acid-Schiff staining and immunofluorescence of type IV collagen and fibronectin) and proteinuria. A significant decrease was also observed in the renal expression of growth factors (connective tissue growth factor and vascular endothelial growth factor) and matrix metalloproteinase inhibitor (plasminogen activator inhibitor-1). These structural and functional changes were associated with significant decreases in renal nuclear SREBP-1 (5.2 in 24 m AL versus 3.3 densitometry units in 24 m CR; P < 0.01) and SREBP-2 (7.1 in 24 m AL versus 4.1 densitometry units in 24 m CR; P < 0.01) protein abundance and renal triglyceride and cholesterol contents. It is interesting that serum leptin level was significantly increased as a function of aging, and CR resulted in significant reduction in serum leptin level. Because it was shown previously that increased renal expression of SREBP-1a per se caused renal lipid accumulation, glomerulosclerosis, and proteinuria, the results suggest that CR modulates age-related renal disease in part by modulation of renal SREBP expression and renal lipid accumulation.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
kidney disease  ISOSrebf1 (Rattus norvegicus)1625196; 1625196protein:altered localization:kidneyRGD 
kidney disease  ISOSrebf2 (Rattus norvegicus)1625196; 1625196protein:altered localization:kidneyRGD 
kidney disease  IEP 1625196; 1625196protein:altered localization:kidneyRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
lipid biosynthetic process  TAS 1625196 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Srebf1  (sterol regulatory element binding transcription factor 1)
Srebf2  (sterol regulatory element binding transcription factor 2)

Genes (Mus musculus)
Srebf1  (sterol regulatory element binding transcription factor 1)
Srebf2  (sterol regulatory element binding factor 2)

Genes (Homo sapiens)
SREBF1  (sterol regulatory element binding transcription factor 1)
SREBF2  (sterol regulatory element binding transcription factor 2)


Additional Information