ISSUE FOCUS 66 FEED & ADDITIVE MAGAZINE February 2026 Mitokine production Mitokines are “signaling molecules that enable communication of local mitochondrial stress to other mitochondria in distant cells and tissues” (Burtscher et al., 2023). Through fibroblast growth factor 21 (FGF21), growth differentiation factor 15 (GDF15), adrenomedullin2 (ADM2) etc, these stress signals are released systemically and coordinate tissue-wide responses, leading to improved growth and resilience. INFLAMMATION AND DISEASE DEFENSE While the negative side of antibiotic growth promoters is well researched and understood (Rahman et al., 2022), science can advance by isolating the positive effects and attempting to offer different pathways to the same benefits. One such lesson can be derived from understanding inflammation pathways and responses. Chronic low-grade intestinal inflammation is common in modern poultry production, due to diet, microbiota shifts, high metabolic demands etc. This inflammation diverts energy from growth to immune responses. AGPs reduce the energy costs of this inflammation in three main ways: • Reduces inflammation through adaptive stress response • Raising the threshold to trigger inflammation • Promoting overall resilience, rather than simply killing pathogens Fernandez Miyakawa et al. suggest, in this emerging model, that disease defense can operate two different actions: resistance to health challenges through reduction of the pathogen load (which is driven by the immune system and is energy costly); and overall resilience by reducing host damage without reducing the pathogen load. AGPs, the authors claim, mainly promote resilience by enhancing mitochondrial stress responses and tissue repair, i.e. more precisely: • Direct mitochondrial stimulation in intestinal epithelial cells • Systemic mitokine signaling coordinating organMitochondria ↓ appetite ↓ glucose homeostasis ↑ taste aversion ↓ appetite ↓ muscle mass ↑ energy expenditure ↑ fatty acid oxidation ↓ glucose ↑ ketogenesis ↑ fatty acid oxidation ↑ insulin sensitivity ↑ glucose uptake ↑ insulin sensitivity ↑ lipolysis ↑ fatty acid oxidation ↑ lipolysis ↓ weight loss ↑ thermogenesis ↑ insulin sensitivity ↑ glucose uptake ↑ β-cell survival ↑ β-cell function ↓ glucagon ↓ inflammation FGF21 GDF15 Nucleus Mitokines GDF15 FGF21 ATF4,5 CHOP misfolded protein Mitochondrial stress response (DELE1, p-elF2a, AMPK) mtDNA damage Figure 1. From Zhang et al., 2024
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