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Differential hepatic lobar gene expression in offspring exposed to altered maternal dietary protein intake
1Endocrine and Metabolism Unit, University of Southampton School of Medicine, Southampton General Hospital, Southampton SO16 6YD, United Kingdom.
Insights
Maternal low-protein diets reduce fibrinogen gene expression and protein in adult offspring. This effect is localized to the left liver lobe and linked to reduced glucocorticoid receptor function.
Area of Science:
- Biochemistry
- Developmental Biology
- Nutritional Science
Background:
- Elevated plasma fibrinogen is a risk factor for coronary heart disease.
- Fibrinogen levels in adults correlate with reduced early growth parameters.
- The liver's unique fetal blood supply creates differential stimuli between left and right lobes.
Purpose of the Study:
- To investigate the impact of maternal low-protein (MLP) diet on fibrinogen gene expression in adult offspring.
- To determine if MLP effects on fibrinogen are consistent between the left and right liver lobes.
- To explore the underlying mechanisms involving glucocorticoid receptor function.
Main Methods:
- Studied fibrinogen gene expression (mRNA copy numbers) in adult offspring of control and MLP dams.
- Assessed fibrinogen concentration in liver lobes.
- Analyzed glucocorticoid receptor binding affinity and mRNA levels in liver lobes.
Main Results:
- MLP offspring showed reduced fibrinogen mRNA and protein specifically in the left liver lobe.
- No significant effects were observed in the right liver lobe or in control offspring.
- Reduced glucocorticoid receptor binding affinity and mRNA levels were found in the left liver lobe of MLP offspring.
Conclusions:
- Maternal dietary protein restriction leads to reduced fibrinogen gene expression, protein, and glucocorticoid receptor function.
- These effects are anatomically restricted to the left liver lobe in adult offspring.
- Early-life nutrition significantly influences long-term gene expression and receptor function in a tissue-specific manner.
Abstract:
Increased plasma fibrinogen concentrations are a recognized risk factor for coronary heart disease, and increased fibrinogen levels in adults are associated with parameters of reduced early growth. We studied fibrinogen gene expression in adult offspring of dams fed either a 20% (control) or an 8% protein diet [maternal low-protein (MLP) rats] during pregnancy and lactation and determined whether any effects were consistent between left and right liver lobes, since the fetal liver has a unique blood supply that produces differential stimuli to the left and right lobes. In MLP offspring, there was a reduction in all three fibrinogen mRNA copy numbers in the left liver lobe [left vs. right lobes for alpha-, beta-, and gamma-fibrinogen (x10(6) copies/ng total RNA): 8.04 vs. 23.16, P<0.001; 4.74 vs. 13.07, P<0.001; and 4.61 vs. 16.38, P = 0.007, respectively], with a parallel reduction in fibrinogen concentration in the left liver lobe (8.53+/-0.33 vs. 10.41 +/-0.65 arbitrary units, P = 0.014, left and right lobes, respectively). No such effect was observed in offspring of control dams. To investigate the underlying mechanism, glucocorticoid receptor function and mRNA levels were studied, since expression of fibrinogen genes is regulated by glucocorticoid hormones. The binding affinity of the high-affinity glucocorticoid receptor was reduced only in the left liver lobe of the MLP offspring (P = 0.02, left. vs. right), with a parallel reduction in this lobe in glucocorticoid receptor mRNA level (P = 0.006, left vs. right). In conclusion, maternal dietary protein restriction reduces fibrinogen gene expression, fibrinogen protein, and mRNA level and binding affinity of glucocorticoid receptors only in the left liver lobe of the adult offspring.