Chronic Glucocorticoid-Rich Milieu and Liver Dysfunction.

Area of Science:

• Endocrinology
• Hepatology
• Metabolic Syndrome

Background:

• Chronic hypercorticosteronemia is linked to metabolic disturbances.
• Neonatal insults can have long-term health consequences.
• Understanding the impact of elevated glucocorticoids on liver function is crucial.

Purpose of the Study:

• To investigate the effects of neonatal MSG-induced hypercorticosteronemia on liver oxidative stress, inflammation, and metabolism in adult rats.
• To evaluate peripheral metabolic markers and insulin resistance.
• To assess hepatic carbohydrate and lipid metabolism.

Main Methods:

• Neonatal monosodium L-glutamate (MSG) administration to induce hypercorticosteronemia.
• Assessment of peripheral metabolic and oxidative stress markers.
• Analysis of liver oxidative stress and inflammatory biomarkers.
• Evaluation of liver carbohydrate and lipid metabolism pathways (mRNA, activity).

Main Results:

• MSG-treated rats exhibited physical changes (hypophagia, low body/liver weight, increased adipose tissue) and metabolic alterations (hyperglycemia, hypertriglyceridemia, insulin resistance).
• Elevated peripheral and hepatic oxidative stress and inflammation markers were observed.
• Key enzymes and transcription factors involved in hepatic glucose and lipid metabolism were upregulated, suggesting increased lipogenesis.

Conclusions:

• Neonatal MSG exposure leads to a chronic hypercorticosteronemic state, resulting in insulin resistance, oxidative stress, and significant hepatic dysfunction in adult rats.
• The observed hepatic changes include inflammation and metabolic alterations favoring lipogenesis, mimicking aspects of metabolic syndrome and Cushing's syndrome.
• A chronic glucocorticoid-rich environment profoundly impacts hepatic glucose metabolism, shifting it towards lipogenesis.