Dietary Protein and Amino Acid Deficiency Inhibit Pancreatic Digestive Enzyme mRNA Translation by Multiple Mechanisms

Area of Science:

• Nutritional biochemistry
• Molecular physiology
• Gastroenterology

Background:

• Chronic amino acid (AA) deficiency, observed in conditions like kwashiorkor, leads to pancreatic atrophy via mammalian target of rapamycin complex 1 (mTORC1) signaling.
• AAs are crucial as substrates and stimulants for mTORC1 and protein synthesis, necessitating an investigation into acute protein and AA deficiency effects on feeding responses.

Purpose of the Study:

• To investigate the impact of acute protein and amino acid deficiency on pancreatic digestive enzyme synthesis following feeding.
• To elucidate the molecular mechanisms, including mTORC1 and translation factor activation, underlying the response to dietary protein and AA availability.

Main Methods:

• ICR/CD-1 mice were fasted and refed with isocaloric diets: control (20% protein), protein-free (0% protein), control (AA-based), and leucine-free.
• Pancreas samples were analyzed for protein synthesis rates, polysomal profiling, and the activation status of key protein translation factors.

Main Results:

• All diets activated the Akt/mTORC1 pathway, but total protein synthesis and polysome formation were significantly inhibited in protein-free and leucine-free diets.
• Protein-free diets partially reduced Akt/mTORC1 signaling and eIF2B activity, while leucine-free diets increased eIF2α phosphorylation and inhibited eIF2B activity.
• Plasma and pancreatic AA levels revealed complex regulation of transport and specific effects on digestive enzyme synthesis.

Conclusions:

• Dietary amino acids are critical regulators of postprandial digestive enzyme synthesis in the pancreas.
• Acute deficiency in dietary AAs can disrupt these regulatory pathways, potentially leading to pancreatic insufficiency and contributing to malnutrition.