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Growth hormone and IGF‐1 deficiency exacerbate high fat diet‐induced endothelial impairment in obese Lewis dwarf rats: implications for vascular aging
Author(s) -
Bailey-Downs Lora C.,
Sosnowska Danuta,
Toth Peter,
Mitschelen Matthew,
Gautam Tripti,
Henthorn Jim,
Ballabh Praveen,
Koller Akos,
Farley Julie,
Sonntag William,
Csiszar Anna,
Ungvari Zoltan
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1057.12
Subject(s) - medicine , endocrinology , oxidative stress , obesity , endothelial dysfunction , inflammation , insulin resistance , hormone , diabetes mellitus , impaired glucose tolerance
Previous studies suggest that age‐related decline in circulating growth hormone (GH) and IGF‐1 levels significantly contribute to vascular dysfunction in aging by impairing cellular oxidative stress resistance pathways. Obesity in the elderly is increasing at alarming rates and elderly individuals are more vulnerable to deleterious cardiovascular effects of obesity than younger individuals. However, the specific mechanisms through which aging, GH/IGF‐1 deficiency and obesity interact to promote the development of cardiovascular disease remain unclear. To test the hypothesis that low circulating GH/IGF‐1 levels exacerbate pro‐oxidant and pro‐inflammatory vascular effects of obesity, GH/IGF‐ 1 deficient Lewis dwarf rats and control rats were fed a standard diet (SD) or a high fat diet (HFD) for 7 months. HFD‐fed Lewis dwarf rats exhibited an increase in blood glucose levels, lower insulin and impaired glucose tolerance compared to HFD‐fed control rats. Analysis of serum cytokine expression indicated that GH/IGF‐1 deficiency exacerbates HFD‐induced inflammation. GH/IGF‐1 deficiency also exacerbated HFD‐induced endothelial dysfunction, oxidative stress and expression of inflammatory cytokines in aortas of Lewis dwarf rats. Our results suggest that GH/IGF‐1 deficiency renders the cardiovascular system more vulnerable to the deleterious effects of obesity.