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Disruption of the Igf2 gene alters hepatic lipid homeostasis and gene expression in the newborn mouse
- Publication Year :
- 2018
- Publisher :
- American Physiological Society, 2018.
-
Abstract
- Newborns with intrauterine growth-restriction are at increased risk of mortality and life-long comorbidities. Insulin-like growth factor-II (IGF2) deficiency in humans, as well as in mice, leads to intrauterine growth restriction and decreased neonatal glycogen stores. The present study aims to further characterize the metabolic and transcriptional consequences of Igf2 deficiency in the newborn. We found that, despite being born significantly smaller than their wild-type ( Igf2+/+) littermates, brain size was preserved in Igf2 knockout ( Igf2−/−), consistent with nutritional deficiency. Histological and triglyceride analyses of newborn livers revealed that Igf2−/−mice are born with hepatic steatosis. Gene expression analysis in Igf2−/−newborn livers showed an alteration of genes known to be dysregulated in chronic caloric restriction, including the most upregulated gene, serine dehydratase. Multiple genes connected with lipid metabolism and/or hepatic steatosis were also upregulated. Ingenuity Pathway Analysis confirmed that the biological functions most altered in livers of Igf2−/−newborns are related to lipid metabolism, with the top upstream regulator predicted to be the peroxisome proliferator-activated receptor alpha, a master regulator of hepatic lipid and carbohydrate homeostasis. Together, our data indicate that Igf2 deficiency leads to a newborn phenotype strongly reminiscent of nutritional deficiency, including growth retardation, increased brain/body weight ratio, hepatic steatosis, and characteristic changes in hepatic gene expression. We propose that in addition to its growth factor proliferating functions, Igf2 may also regulate growth by altering the expression of genes that control nutrient metabolism in the newborn.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
animal structures
endocrine system diseases
Physiology
Endocrinology, Diabetes and Metabolism
medicine.medical_treatment
Intrauterine growth restriction
Gene Expression
030209 endocrinology & metabolism
Biology
03 medical and health sciences
chemistry.chemical_compound
Mice
0302 clinical medicine
Insulin-Like Growth Factor II
Physiology (medical)
Internal medicine
Gene expression
medicine
Animals
Homeostasis
Mice, Knockout
Carbohydrate homeostasis
Glycogen
Growth factor
Gene Expression Profiling
Lipid metabolism
medicine.disease
Lipid Metabolism
female genital diseases and pregnancy complications
Fatty Liver
030104 developmental biology
Endocrinology
Phenotype
chemistry
Animals, Newborn
Liver
Steatosis
Research Article
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....695fcc4c40e3a518f37606020663017b