Zn64 aspartate modulates inflammation, tryptophan metabolism, and pancreatic function in diet-induced obesity.

Obesity-induced metabolic syndrome is characterized by chronic inflammation, hormonal imbalance, and altered neurotransmitter metabolism. Zinc plays a critical role in immune regulation and energy balance; however, the effects of isotopically modified chelate complexes in metabolic functions remain unexplored. This study investigated the therapeutic effects of isotopically enriched Zn64 Aspartate in a rat model of diet-induced obesity, focusing on inflammation, adipokine secretion, and tryptophan metabolism across serum, brain, duodenum, the pancreas, and adipose tissues. Male Wistar rats were fed a high-fat diet to induce obesity and treated with Zn64 Aspartate. Proinflammatory and anti-inflammatory cytokine levels, resistin, ghrelin, serotonin, tryptophan concentrations, and enzymatic activities of tryptophan hydroxylase (TPH), indoleamine 2,3-dioxygenase (IDO), and monoamine oxidase (MAO) were analyzed. Zn64 Aspartate significantly reduced pro-inflammatory cytokines and resistin levels while normalizing ghrelin. It enhanced serotonin levels and modulated TPH, IDO, and MAO activities in a tissue-specific manner, favoring serotonergic over kynurenine pathway metabolism. A decrease in pancreatic fibrosis, glycogen content, and an increase in the number of insulin-positive β-cells were observed in obese rats treated with Zn64 Aspartate, compared with the obese group. Conclusively, Zn64 Aspartate shows promise as a metabolic modulator by attenuating inflammation and restoring neuroendocrine balance in obesity. Further studies are warranted to validate its therapeutic potential.