Anti-inflammatory but not insulin-sensitizing: Effects of docosahexaenoic acid abomasal infusions on adipose tissue...

Supplementing dairy cow diets with n-3 fatty acids has been an alternative nutritional intervention to reduce systemic inflammation and improve reproductive function. Docosahexaenoic acid (C22:6n-3; DHA) is one of the n-3 fatty acids with the strongest anti-inflammatory effects in humans and animals. However, it is unknown if DHA modulates adipose tissue (AT) function and inflammatory responses in dairy cows. Our objective was to evaluate the effects of DHA on AT insulin sensitivity and AT macrophage infiltration in mid-lactation dairy cows. Eight ruminally cannulated multiparous Holstein cows (97 ± 37 DIM, 49.2 ± 3.3 kg/d milk) were enrolled in a 4 × 4 Latin square design. Cows were infused abomasally with 0, 2, 4, or 6 g/d DHA for 11 d, with 10-d washouts between infusion periods. Subcutaneous AT was collected on d 11 of each period. Isoproterenol- (ISO, 1 μM) stimulated lipolysis and insulin (1 μg/L) inhibition of lipolysis were determined using an ex vivo explant culture by measuring glycerol release (µmol/mg AT). Macrophage abundance was evaluated by immunohistochemistry using CD172a antibody, and images were analyzed in ImageJ to quantify CD172a signal intensity (total area, µm²). The ISO increased lipolysis (4.82-fold vs. unstimulated) in AT explants from all treatments. Additionally, insulin inhibited ISO-stimulated lipolysis (-45.0%), and this response was unaffected by DHA treatment, indicating that DHA had no impact on insulin sensitivity. Increasing DHA dose (0, 2, 4, 6 g/d) linearly decreased AT macrophage abundance when measured as CD172a⁺ % area of tissue sections (0.17%, 0.11%, 0.10%, 0.06% ± 0.03%). Our results suggest that DHA does not alter lipolytic and insulin responses in AT in mid-lactation cows. However, it reduces inflammatory responses in AT by decreasing macrophage trafficking into the adipose organ. The implications of limiting macrophage infiltration into AT by supplementing DHA warrant further research.