Protein calorie restriction affects nonhepatic IGF-I production and the lymphoid system: Studies using the liver-specific IGF-I gene-deleted mouse model

Wilson Mejia Naranjo, Shoshana Yakar, Myriam Sanchez-Gomez, Adriana Umana Perez, Jennifer Setser, Derek Leroith

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2233-2241
Number of pages9
JournalEndocrinology
Volume143
Issue number6
DOIs
StatePublished - 2002

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Insulin-Like Growth Factor I
Liver
Genes
Proteins
IGF Type 1 Receptor
Spleen
Up-Regulation
Protein-Energy Malnutrition
Messenger RNA
Insulin-Like Growth Factor Binding Protein 3
Dietary Proteins
Ribonucleases
Nutritional Status
Northern Blotting
Flow Cytometry
Homeostasis
B-Lymphocytes
Diet

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Protein calorie restriction affects nonhepatic IGF-I production and the lymphoid system : Studies using the liver-specific IGF-I gene-deleted mouse model. / Naranjo, Wilson Mejia; Yakar, Shoshana; Sanchez-Gomez, Myriam; Perez, Adriana Umana; Setser, Jennifer; Leroith, Derek.

In: Endocrinology, Vol. 143, No. 6, 2002, p. 2233-2241.

Research output: Contribution to journalArticle

Naranjo, Wilson Mejia ; Yakar, Shoshana ; Sanchez-Gomez, Myriam ; Perez, Adriana Umana ; Setser, Jennifer ; Leroith, Derek. / Protein calorie restriction affects nonhepatic IGF-I production and the lymphoid system : Studies using the liver-specific IGF-I gene-deleted mouse model. In: Endocrinology. 2002 ; Vol. 143, No. 6. pp. 2233-2241.
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