IGF-1 induces rat glomerular mesangial cells to accumulate triglyceride.
Rat glomerular mesangial cells (MC) become lipid-laden foam cells when they are exposed to IGF-1. IGF-1 increased accumulation of triglyceride (TG) 2.5-fold in MC after 7 days. TG accumulation resulted from enhanced macropinocytosis and decreased efflux secondary to a 40-50% reduction in peroxisome proliferator-activated receptor (PPAR)-delta (PPARdelta). There was no evidence of primary or secondary changes in cholesterol or TG synthesis, increased uptake by LDL or scavenger receptors, or reduced efflux via ATP-binding cassette A-1. Although the lipid moiety taken up can be influenced by the concentration of cholesterol or TG in the medium, in standard medium MC preferentially accumulate TG. TG-rich MC foam cells fail to contract in response to angiotensin II (Berfield AK, Andress DL, and Abrass CK. Kidney Int 62: 1229-1237, 2002); however, their migratory response to IGF binding protein-5 is unaffected. This differs from cholesterol loading, which impairs both phagocytosis and migration. These findings have important implications for understanding the mechanisms that contribute to lipid accumulation in MC and the functional consequences of different forms of foam cells. These observations are relevant to understanding vascular disease and progressive renal diseases that are accelerated by abnormalities in lipid metabolism.
Berfield
Anne K
AK
Univ. of Washington School of Medicine and Department of Medicine, Veterans Affairs Puget Sound Health Care System, 1660 South Columbian Way, Seattle, WA 98108, USA.
Chait
Alan
A
Oram
John F
JF
Zager
Richard A
RA
Johnson
Ali C
AC
Abrass
Christine K
CK
D000818:Animals; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology* / Q000502:physiology; D050356:Lipid Metabolism; D050527:Mesangial Cells / Q000187:drug effects* / Q000378:metabolism; D010873:Pinocytosis; D051381:Rats; D014280:Triglycerides / Q000378:metabolism*
D014280:Triglycerides; D007334:Insulin-Like Growth Factor I; D002784:Cholesterol