ArticleBiogerontology2025
Antibiotic exposure alters the LEAP-2/ghrelin axis and anti-inflammatory tone in aged male rat liver and adipose tissue.
Article in Biogerontology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Liver-expressed antimicrobial peptide-2 (LEAP-2), the endogenous antagonist of the ghrelin receptor (GHSR1a), counterbalances ghrelin in an energy- and inflammation-dependent manner. Aging is accompanied by endocrine and immunometabolic shifts that may influence this axis. We investigated whether a short course of broad-spectrum antibiotics (vancomycin-metronidazole-neomycin-ampicillin; VMNA) alters LEAP-2 and ghrelin levels in the liver and epididymal white adipose tissue (WAT) of aged male rats, and whether these changes coincide with modifications in IL-10, TNF-α, and IL-1β. Antibiotic treatment lowered LEAP-2 in both liver and WAT. Ghrelin decreased in both tissues, but the reduction reached significance only in WAT, whereas the hepatic decrease was nonsignificant. Consequently, the LEAP-2/ghrelin ratio declined in the liver and showed a nonsignificant upward trend in WAT. Inflammatory profiling revealed that IL-10 decreased in both tissues, whereas TNF-α and IL-1β remained unchanged. These findings demonstrate that even a one-week antibiotic regimen induces tissue-specific alterations in the LEAP-2/ghrelin axis-characterized by reduced hepatic LEAP-2 signaling, suppressed adipose ghrelin, and diminished anti-inflammatory tone. Overall, the data suggest that aged male rats exhibit heightened vulnerability to antibiotic-induced perturbations in LEAP-2/ghrelin regulation, underscoring the interplay between microbiota-related influences, inflammaging, and age-associated metabolic imbalance.
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