66 Targeting inflammation with ω-3 polyunsaturated fatty acid nutraceutical interventions improved lipid flux and partially restored lipid metabolic indicators in heat-stressed finishing wethers.

Abstract Chronic heat stress disrupts fat mobilization and metabolism, leading to reduced energy availability and metabolic inefficiencies in livestock. The present study aimed to determine if targeting heat stress-induced inflammation with anti-inflammatory nutraceutical supplements would improve lipid homeostasis in finishing wethers. We hypothesized that ω-3 polyunsaturated fatty acid (ω-3 PUFA) nutraceuticals would reduce systemic inflammation and in turn mitigate the adverse effects of heat stress on key indicators of lipid storage, mobilization, and metabolism. In Experiment 1, commercial Polypay-cross wether lambs (40.8 ± 0.7 kg) were maintained under heat stress (40 °C, 35% humidity) or were pair-fed under thermoneutral conditions (19 °C, 15% humidity; n = 11) for 30 d. Heat-stressed lambs were randomly assigned to receive: 1) clinical-dose dexamethasone injections (0.15 mg/kg, IM) every 72 h (n = 11), 2) oral 1200-mg boluses of ω-3 PUFA-rich fish oil capsules twice daily (n = 11), or 3) placebo injections/capsules (n = 11). In Experiment 2, heat-stressed wethers received daily oral ω-3 PUFA Ca2+ salts supplementation (0.42 g/kg bodyweight; n = 11) or a placebo (n = 12). Lipid mobilization was assessed ex vivo from primary visceral adipose tissue by measuring epinephrine-stimulated release of non-esterified fatty acids (NEFA) and glycerol. Semitendinosus muscle lipid content and lipid droplet dynamics were quantified by Oil Red O staining, and expression of lipid metabolism enzymes (CD36, PPARα, PPARγ, ACSL1) were analyzed via protein immunoblot. Heat stress reduced (P ≤ 0.05) fatty acid mobilization at all epinephrine concentrations, indicating limited energy availability. Fish oil restored (P ≤ 0.05), and ω-3 Ca2+ salts tended to restore (P = 0.06) ex vivo NEFA release. All three interventions improved (P ≤ 0.05) ex vivo glycerol mobilization. Following heat stress, semitendinosus lipid droplet density was reduced (P ≤ 0.05) by 34% in Experiment 1 and total lipid area tended to be reduced (P = 0.09) by 21% in Experiment 2, with no recovery from any of the interventions. Semitendinosus CD36 content was suppressed (P ≤ 0.05) and PPARγ tended to be suppressed (P = 0.08) by heat stress in Experiment 2, and PPARα was elevated (P ≤ 0.05) by heat stress in Experiment 1. This indicates a metabolic shift toward greater fatty acid oxidation. Moreover, ACSL1 content was unchanged in either experiment, indicating stable fatty acid activation capacity. These findings show that heat stress-induced systemic inflammation impairs lipid mobilization but may increase muscle lipid metabolism. Anti-inflammatory interventions mitigated some of these effects, but unresolved deficits in glycerol mobilization and some metabolic pathways suggest that inflammation is not the sole driver of heat stress-induced lipid dysregulation. Nevertheless, targeting inflammation clearly benefited lipid flux in heat-stressed livestock.