title: Growth hormone and IGF-1 deficiency exacerbate high-fat diet-induced endothelial impairment in obese Lewis dwarf rats: implications for vascular aging.
abstract: Previous studies suggest that the age-related decline in circulating growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels significantly contribute to vascular dysfunction in aging by impairing cellular oxidative stress resistance pathways. Obesity in elderly individuals is increasing at alarming rates, and there is evidence suggesting that elderly individuals are more vulnerable to the 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 the pro-oxidant and proinflammatory vascular effects of obesity, GH/IGF-1-deficient Lewis dwarf rats and heterozygous control rats were fed either a standard diet or a high-fat diet (HFD) for 7 months. Feeding an HFD resulted in similar relative weight gains and increases in body fat content in Lewis dwarf rats and control rats. HFD-fed Lewis dwarf rats exhibited a relative increase in blood glucose levels, lower insulin, and impaired glucose tolerance as compared with HFD-fed control rats. Analysis of serum cytokine expression signatures indicated that chronic GH/IGF-1 deficiency exacerbates HFD-induced inflammation. GH/IGF-1 deficiency also exacerbated HFD-induced endothelial dysfunction, oxidative stress, and expression of inflammatory markers (tumor necrosis factor-α, ICAM-1) in aortas of Lewis dwarf rats. Overall, our results are consistent with the available clinical and experimental evidence suggesting that GH/IGF-1 deficiency renders the cardiovascular system more vulnerable to the deleterious effects of obesity.
authors.affiliation: Reynolds Oklahoma Center on Aging, Donald W. Reynolds Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
authors.forename: Lora C
authors.initials: LC
authors.lastname: Bailey-Downs
authors.forename: Danuta
authors.initials: D
authors.lastname: Sosnowska
authors.forename: Peter
authors.initials: P
authors.lastname: Toth
authors.forename: Matthew
authors.initials: M
authors.lastname: Mitschelen
authors.forename: Tripti
authors.initials: T
authors.lastname: Gautam
authors.forename: Jim C
authors.initials: JC
authors.lastname: Henthorn
authors.forename: Praveen
authors.initials: P
authors.lastname: Ballabh
authors.forename: Akos
authors.initials: A
authors.lastname: Koller
authors.forename: Julie A
authors.initials: JA
authors.lastname: Farley
authors.forename: William E
authors.initials: WE
authors.lastname: Sonntag
authors.forename: Anna
authors.initials: A
authors.lastname: Csiszar
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Ungvari
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects*; D004392:Dwarfism / Q000097:blood / Q000378:metabolism; D005951:Glucose Tolerance Test; D013006:Growth Hormone / Q000172:deficiency*; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000172:deficiency*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D008297:Male; D009765:Obesity / Q000097:blood / Q000378:metabolism*; D018384:Oxidative Stress; D051381:Rats; D011917:Rats, Inbred Lew; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D001786:Blood Glucose; D016207:Cytokines; D007328:Insulin; D014409:Tumor Necrosis Factor-alpha; C548904:insulin-like growth factor-1, rat; D018799:Intercellular Adhesion Molecule-1; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone
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