Targeting Inflammation with Dietary ω-3 Polyunsaturated Fatty Acids Improved Lipid Mobilization and Flux in Heat-Stressed Wether Lambs

<b>Background/Objectives:</b> Chronic heat stress impairs lipid mobilization from adipocytes, which reduces substrate availability for muscle metabolism. Systemic inflammation is a key facilitative response to heat stress, and we sought to determine if mitigating inflammation in heat-stressed wether lambs would improve lipid flux. <b>Methods:</b> Two cohorts of commercial feedlot lambs were heat stressed for 30 days. In study 1, heat-stressed lambs received dexamethasone injections every 3 days, fish oil capsules twice daily, or no intervention. In study 2, heat-stressed lambs received daily boluses of ω-3 polyunsaturated fatty acid Ca²⁺ salts (ω-3 PUFA) or no intervention. <b>Results:</b> In both studies, heat stress reduced <i>ex vivo</i> epinephrine-stimulated free fatty acid and glycerol mobilization from visceral adipose tissue. These deficits were partially resolved by fish oil and fully resolved by ω-3 PUFA. In study 1, fish oil recovered heat stress-induced deficits in circulating triglycerides and HDL-cholesterol but not in circulating free fatty acids. Fish oil and dexamethasone resolved the increase in muscle PPARα, indicating less lipid utilization for metabolism. In study 2, ω-3 PUFA resolved heat stress-induced deficits in muscle CD36 and PPARγ, indicating improved lipid uptake capacity. However, interventions did not resolve reduced intramuscular lipid content in either study. <b>Conclusions:</b> We conclude that inflammation was a primary facilitator of impaired lipid mobilization in heat-stressed lambs but was not the sole driver of lipid dysregulation. Nevertheless, targeting inflammation was a beneficial strategy for improving lipid flux during chronic heat stress.