The stressful condition as a nutritionally dependent adaptive dichotomy

Area of Science:

• Endocrinology
• Metabolic Regulation
• Stress Response

Background:

• The body initiates defense and repair mechanisms following injury, involving cytokines and counterregulatory hormones.
• These responses lead to insulin resistance, altered lipid metabolism, and changes in thyroid hormone regulation.

Purpose of the Study:

• To elucidate the interplay between cytokines, hormones, and metabolic adaptations during the stress response.
• To investigate the role of transthyretin (TTR) and retinol-binding protein (RBP) in thyroid and retinoid hormone transport and activation.
• To understand how nutritional status influences these acute-phase responses and survival outcomes.

Main Methods:

• Analysis of cytokine-induced metabolic events and hormonal changes in response to injury.
• Assessment of thyroid hormone deiodination (5'-DA) and its impact on T3 levels.
• Evaluation of liver and tissue adaptations, including TTR and RBP synthesis and transport.

Main Results:

• Injury triggers sustained hypercortisolemia and down-regulation of the hypothalamo-pituitary-thyroid axis.
• Inhibition of 5'-DA leads to low T3 levels, sparing energy and nitrogen.
• Cytokines stimulate liver 5'-DA, suppress TTR synthesis, increasing free T4 and retinol, creating a transient hyperthyroid/hyperretinoid state.

Conclusions:

• The body's stress response involves complex hormonal and metabolic shifts, including altered thyroid and retinoid signaling.
• Transthyretin (TTR) and retinol-binding protein (RBP) are crucial for transporting and activating thyroid and retinoid hormones.
• Impaired nutritional status compromises these adaptive responses, hindering survival during critical illness.