Lipolysis modulates the biosynthesis of inflammatory lipid mediators derived from linoleic acid in adipose tissue of periparturient dairy cows

摘要

Oxidized linoleic acid metabolites (OXLAM) areproducts of adipocyte lipolysis with the potential tomodulate adipose tissue (AT) lipid metabolism andinflammation. In periparturient cows, linoleic acid ispreferentially mobilized from AT during lipolysis byhormone-sensitive lipase (HSL) compared with otherpolyunsaturated fatty acids. Enzymatic and nonenzymaticreactions generate OXLAM from linoleic acid.Among OXLAM, 9-, 10-, and 12-hydroxy-octadecadienoicacids (HODE) are associated with pro-inflammatoryresponses, whereas 9- and 13-oxo-octadecadienoicacids (oxoODE) and 13-HODE can facilitate inflammationresolution and promote lipogenesis. This studyevaluated the effect of HSL activity on OXLAM biosynthesisusing subcutaneous AT explants collectedfrom multiparous dairy cows at 10 d before and againat 10 and 24 d after calving. Explants were treatedfor 3 h without or with the β-adrenergic agonist isoproterenol(ISO; 1 μM; MilliporeSigma, Burlington,MA) to induce HSL activity. The contribution of HSLto OXLAM biosynthesis was determined by inhibitingits activity with CAY10499 (2 μM; Cayman Chemical,Ann Arbor, MI). After treatments, media and explantswere collected for lipidomic analysis using HPLC–tandemmass spectroscopy. Results indicated that ISOincreased the biosynthesis of 9-, 12-, and 13-HODEand 9-oxoODE, and this effect was reduced at 24 dafter calving. Inhibiting HSL activity partially reversedISO effects on HODE and 9-oxoODE. Our ex vivomodel demonstrated for the first time a direct effectof HSL activity on the biosynthesis of OXLAM in AT,especially at 10 d before and 10 d after calving. Thebiosynthesis of anti-inflammatory OXLAM is limitedduring the first weeks after parturition and may promoteAT inflammation and lipolytic responses to negativeenergy balance. These results indicate that HSLactivity releases linoleic acid for OXLAM biosynthesisin concentrations of a magnitude that may bypass theneed for the activation of phospholipases linked withthe inflammatory cascade and thus supports, in part,lipolysis-driven inflammation within AT of periparturientcows.