title: Selective protein depletion impairs bone growth and causes liver fatty infiltration in female rats: prevention by Spirulina alga.
abstract: Chronic protein malnutrition leads to child mortality in developing countries. Spirulina alga (Spi), being rich in protein and growing easily, is a good candidate as supplementation. We showed that Spi completely prevents bone growth retardation and liver disturbances observed in young rats fed a low protein diet. This supports Spi as a useful source of vegetable protein to fight against protein malnutrition.
  
  
  
  Chronic malnutrition is a main factor of child mortality in developing countries. A low protein diet impairs whole-body growth and leads to fatty liver in growing rats. Spi has great potential as a supplementation as it has a 60 % protein content and all essential amino acids. However, its specific impact on bone growth and the related secretion of hepatokines have not yet been studied.
  
  
  
  To address this question, 6-week-old female rats were fed isocaloric diets containing 10 % casein, 5 % casein, or 5 % casein + 5 % protein from Spi during 9 weeks. Changes in tibia geometry, microarchitecture, BMC, BMD, and biomechanical properties were analyzed. Serum IGF-I, FGF21, follistatin, and activin A were assessed as well as their hepatic gene expressions in addition to those of Sirt1, Ghr, and Igf1r. Hepatic fat content was also assessed.
  
  
  
  A low protein diet altered bone geometry and reduced proximal tibia BMD and trabecular bone volume. In addition, it increased hepatic fat content and led to hepatic GH resistance by decreasing serum IGF-I and increasing serum FGF21 without altering serum activin A and follistatin. Spi prevented low protein diet-induced bone, hepatic, and hormonal changes, and even led to higher biomechanical properties and lower hepatic fat content in association with specific InhbA and Follistatin expression changes vs. the 10 % casein group.
  
  
  
  Altogether our results demonstrate the preventive impact of Spi on bone growth delay and hepatic GH resistance in conditions of isocaloric dietary protein deficiency.
authors.affiliation: Division of Bone Diseases, Department of Internal Medicine Specialties, Geneva University Hospitals and Faculty of Medicine, Rue Gabrielle-Perret-Gentil, 4, CH1211, Geneva, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Fournier
authors.affiliation: Division of Bone Diseases, Department of Internal Medicine Specialties, Geneva University Hospitals and Faculty of Medicine, Rue Gabrielle-Perret-Gentil, 4, CH1211, Geneva, Switzerland.
authors.forename: R
authors.initials: R
authors.lastname: Rizzoli
authors.affiliation: Department of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland.
authors.forename: K
authors.initials: K
authors.lastname: Bouzakri
authors.affiliation: Division of Bone Diseases, Department of Internal Medicine Specialties, Geneva University Hospitals and Faculty of Medicine, Rue Gabrielle-Perret-Gentil, 4, CH1211, Geneva, Switzerland. Patrick.Ammann@hcuge.ch.
authors.forename: P
authors.initials: P
authors.lastname: Ammann
mesh_terms: D028341:Activins / Q000097:blood; D000818:Animals; D001846:Bone Development; D018753:Diet, Protein-Restricted / Q000009:adverse effects; D019587:Dietary Supplements; D005234:Fatty Liver / Q000517:prevention & control*; D005260:Female; D005346:Fibroblast Growth Factors / Q000097:blood; D038681:Follistatin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D053545:Spirulina
chemical_list: D038681:Follistatin; C422405:activin A; C414620:fibroblast growth factor 21; C548904:insulin-like growth factor-1, rat; D028341:Activins; D005346:Fibroblast Growth Factors; D007334:Insulin-Like Growth Factor I
keywords: Fatty liver; Protein malnutrition; Skeletal growth; Spirulina alga