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Transcription profiling in the liver of undernourished male rat offspring reveals altered lipid metabolism pathways and predisposition to hepatic steatosis.
- Source :
-
American journal of physiology. Endocrinology and metabolism [Am J Physiol Endocrinol Metab] 2019 Dec 01; Vol. 317 (6), pp. E1094-E1107. Date of Electronic Publication: 2019 Oct 22. - Publication Year :
- 2019
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Abstract
- Clinical and animal studies have reported an association between low birth weight and the development of nonalcoholic fatty liver disease (NAFLD) in offspring. Using a model of prenatal maternal 70% food restriction diet (FR30) in the rat, we previously showed that maternal undernutrition predisposes offspring to altered lipid metabolism in adipose tissue, especially on a high-fat (HF) diet. Here, using microarray-based expression profiling combined with metabolic, endocrine, biochemical, histological, and lipidomic approaches, we assessed whether FR30 procedure sensitizes adult male offspring to impaired lipid metabolism in the liver. No obvious differences were noted in the concentrations of triglycerides, cholesterol, and bile acids in the liver of 4-mo-old FR30 rats whichever postweaning diet was used. However, several clues suggest that offspring's lipid metabolism and steatosis are modified by maternal undernutrition. First, lipid composition was changed (i.e., higher total saturated fatty acids and lower elaidic acid) in the liver, whereas larger triglyceride droplets were observed in hepatocytes of undernourished rats. Second, FR30 offspring exhibited long - term impact on hepatic gene expression and lipid metabolism pathways on a chow diet. Although the transcriptome profile was globally modified by maternal undernutrition, cholesterol and bile acid biosynthesis pathways appear to be key targets, indicating that FR30 animals were predisposed to impaired hepatic cholesterol metabolism. Third, the FR30 protocol markedly modifies hepatic gene transcription profiles in undernourished offspring in response to postweaning HF. Overall, FR30 offspring may exhibit impaired metabolic flexibility, which does not enable them to properly cope with postweaning nutritional challenges influencing the development of nonalcoholic fatty liver.
- Subjects :
- Animals
Bile Acids and Salts metabolism
Cholesterol metabolism
Fatty Acids metabolism
Fatty Liver metabolism
Fatty Liver pathology
Female
Gene Expression Profiling
Hepatocytes metabolism
Hepatocytes pathology
Lipid Droplets pathology
Liver pathology
Male
Oleic Acids metabolism
Pregnancy
Prenatal Exposure Delayed Effects metabolism
Prenatal Exposure Delayed Effects pathology
Prenatal Nutritional Physiological Phenomena genetics
Rats
Triglycerides metabolism
Fatty Liver genetics
Lipid Metabolism genetics
Liver metabolism
Malnutrition
Pregnancy Complications
Prenatal Exposure Delayed Effects genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1555
- Volume :
- 317
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Endocrinology and metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 31638854
- Full Text :
- https://doi.org/10.1152/ajpendo.00291.2019