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Developmental changes in mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase gene expression in rat liver,
S Thumelin1, M Forestier, J Girard
1Centre de Recherche sur l'Endocrinologie Moléculaire et le Développement, CNRS, Meudon-Bellevue, France.
Abstract:
The tissue-specific expression of the mitochondrial 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase gene was studied in 15-day-old suckling rats. The mRNA and protein were present in liver, intestine and kidney, but were absent from brain, heart, skeletal muscles, brown and white adipose tissues. Kidney-cortex mitochondria from suckling rats were able to produce low amounts of ketone bodies from oleate. Hepatic, intestinal and renal HMG-CoA synthase mRNA levels increased slowly during foetal life and markedly after birth. The postnatal increase in liver HMG-CoA synthase mRNA could be due to the increase in plasma glucagon levels, since it rapidly induced the accumulation of HMG-CoA synthase mRNA in cultured foetal hepatocytes. Hepatic, intestinal and renal HMG-CoA synthase mRNA levels remained elevated throughout the suckling period or in rats weaned on to a high-fat carbohydrate-free diet (HF), but decreased by 50% in the liver and totally disappeared from the intestine and the kidney of rats weaned on to a high-carbohydrate low-fat diet (HC). When HC-weaned rats were fed on a HF-diet for a week, HMG-CoA synthase mRNA was re-induced in the intestine and the kidney. The role of hormones and nutrients in the regulation of HMG-CoA synthase gene expression is discussed.
Insights
Mitochondrial 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase gene expression is specific to liver, intestine, and kidney in suckling rats. Diet significantly impacts HMG-CoA synthase mRNA levels, highlighting nutrient regulation.
Area of Science:
- Biochemistry
- Molecular Biology
- Physiology
Background:
- Mitochondrial 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase is crucial for ketone body synthesis.
- Understanding its tissue-specific expression and regulation is vital for metabolic studies.
Purpose of the Study:
- To investigate the tissue-specific expression of the mitochondrial HMG-CoA synthase gene in suckling rats.
- To explore the influence of diet and hormones on HMG-CoA synthase gene expression.
Main Methods:
- Studied mRNA and protein expression in various rat tissues.
- Assessed ketone body production in kidney mitochondria.
- Analyzed gene expression changes in response to different diets (high-fat, high-carbohydrate) and hormonal stimulation (glucagon).
Main Results:
- Mitochondrial HMG-CoA synthase mRNA and protein were detected in liver, intestine, and kidney, but not in brain or muscle.
- Kidney mitochondria produced low levels of ketone bodies.
- Gene expression increased postnatally and was sustained by high-fat diets, but decreased on high-carbohydrate diets.
- Glucagon stimulated HMG-CoA synthase mRNA accumulation in cultured hepatocytes.
Conclusions:
- Tissue-specific expression of mitochondrial HMG-CoA synthase is established early in development.
- Dietary composition, particularly fat and carbohydrate content, plays a significant role in regulating HMG-CoA synthase gene expression.
- Hormonal factors like glucagon may contribute to the postnatal regulation of this gene.