Protein calorie restriction affects nonhepatic IGF-I production and the lymphoid system: studies using the liver-specific IGF-I gene-deleted mouse model.
Nutritional status is a critical factor that modulates the responsiveness of the liver to GH and the resulting production of endocrine (mostly liver-derived) IGF-I. Using a conditional Cre/lox P system, we have established a liver-specific IGF-I-deficient mouse model. Despite the reduction in the circulating IGF-I (75%), the growth parameters are normal, except for the reduced spleen size, providing a unique model to study the effect of protein restriction on the autocrine/paracrine GH/IGF-I axis. To determine the effects of protein calorie malnutrition on the spleen, liver-specific IGF-I-deficient mice were assigned to one of four isocaloric diets, differing in the protein content (20, 12, 4, and 0%), for a period of 10 d. A low protein intake decreased the nonhepatic IGF-I secretion into the circulation, whereas it caused an increase in the level of circulating GH. This supports the view that nonhepatic IGF-I production contributes to circulating IGF-I levels. The lack of dietary protein led to an up-regulation of GH and IGF-I receptors expression in the spleen, whereas the IGF-I mRNA remained unchanged, as was demonstrated by flow cytometry and ribonuclease protection assay. B lymphocytes seem to be responsible for the up-regulated GH/IGF-I receptor expression. Northern blot analysis showed an up-regulation of IGF-binding protein-3 mRNA levels, which suggests that the protein deprivation may lead to an increased sequestration of circulating or locally synthesized IGF-I. These results support the hypothesis that the splenic GH/IGF-I axis responds to the nutritional stress caused by a low protein intake, to maintain the tissue homeostasis.
Naranjo
Wilson Mejia
WM
Department of Chemistry, National University of Columbia, Bogotá, Cundinamarca.
Yakar
Shoshana
S
Sanchez-Gomez
Myriam
M
Perez
Adriana Umana
AU
Setser
Jennifer
J
LERoith
Derek
D
D000818:Animals; D019898:Autocrine Communication / Q000187:drug effects; D015152:Blotting, Northern; D015153:Blotting, Western; D001835:Body Weight / Q000502:physiology; D004032:Diet; D004044:Dietary Proteins / Q000008:administration & dosage; D004435:Eating / Q000502:physiology; D005434:Flow Cytometry; D019793:Fluorescein; D005456:Fluorescent Dyes; D013006:Growth Hormone / Q000097:blood / Q000502:physiology; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis* / Q000235:genetics*; D008099:Liver / Q000378:metabolism*; D008221:Lymphoid Tissue / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D023282:Nuclease Protection Assays; D009929:Organ Size / Q000502:physiology; D019899:Paracrine Communication / Q000187:drug effects; D011502:Protein-Energy Malnutrition / Q000378:metabolism*; D013154:Spleen / Q000033:anatomy & histology / Q000166:cytology / Q000254:growth & development
D004044:Dietary Proteins; D005456:Fluorescent Dyes; D007328:Insulin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D019793:Fluorescein