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

Abstract

Oxidized linoleic acid metabolites (OXLAM) are products of adipocyte lipolysis with the potential to modulate adipose tissue (AT) lipid metabolism and inflammation. In periparturient cows, linoleic acid is preferentially mobilized from AT during lipolysis by hormone-sensitive lipase (HSL) compared with other polyunsaturated fatty acids. Enzymatic and nonenzymatic reactions generate OXLAM from linoleic acid. Among OXLAM, 9-, 10-, and 12-hydroxy-octadecadienoic acids (HODE) are associated with pro-inflammatory responses, whereas 9-and 13-oxo-octadecadienoic acids (oxoODE) and 13-HODE can facilitate inflammation resolution and promote lipogenesis. This study evaluated the effect of HSL activity on OXLAM biosynthesis using subcutaneous AT explants collected from multiparous dairy cows at 10 d before and again at 10 and 24 d after calving. Explants were treated for 3 h without or with the β-adrenergic agonist isoproterenol (ISO; 1 µM; MilliporeSigma, Burlington, MA) to induce HSL activity. The contribution of HSL to OXLAM biosynthesis was determined by inhibiting its activity with CAY10499 (2 µM; Cayman Chemical, Ann Arbor, MI). After treatments, media and explants were collected for lipidomic analysis using HPLC-tandem mass spectroscopy. Results indicated that ISO increased the biosynthesis of 9-, 12-, and 13-HODE and 9-oxoODE, and this effect was reduced at 24 d after calving. Inhibiting HSL activity partially reversed ISO effects on HODE and 9-oxoODE. Our ex vivo model demonstrated for the first time a direct effect of HSL activity on the biosynthesis of OXLAM in AT, especially at 10 d before and 10 d after calving. The biosynthesis of anti-inflammatory OXLAM is limited during the first weeks after parturition and may pro-mote AT inflammation and lipolytic responses to negative energy balance. These results indicate that HSL activity releases linoleic acid for OXLAM biosynthesis in concentrations of a magnitude that may bypass the need for the activation of phospholipases linked with the inflammatory cascade and thus supports, in part, lipolysis-driven inflammation within AT of periparturient cows.

Increased adipose tissue lipolysis in dairy cows with fatty liver is associated with enhanced autophagy activity

“…Pharmacological ISO treatment of 3T3-L1 cells and adipose tissue in mice stimulated lipolysis and release of fatty acids (Chitraju et al, 2017). A similar effect was detected in adipose tissue of periparturient dairy cows where incubation with ISO induced the activity of HSL and increased release of linoleic acid (Andres Contreras et al, 2020). This effect was confirmed in the present study through the increased abundance of ATGL, the ratio of p-HSL to HSL, and the glycerol content along with decreased abundance of PLIN1 in calf adipocytes.…”

Redox Regulation of Lipid Mobilization in Adipose Tissues

“…A comprehensive characterization of OS during the periparturient period or health events in AT of dairy cows is currently lacking. However, there is evidence for the presence of OS in AT of these cows as we detected isoprostanes, the gold standard OS biomarker, in AT during the first three weeks after calving [125].…”

Symposium review: Mechanistic insights into adipose tissue inflammation and oxidative stress in periparturient dairy cows

“…In the meantime, plasma 9-HODE remained unchanged (Contreras et al, 2017a). When we evaluated the production of HODE in AT during the PP, we found that HSL activity is determinant in the synthesis of these oxylipids (Contreras et al, 2020). Most importantly, HSL releases linoleic acid for HODE biosynthesis in concentrations of a magnitude that may bypass the need for the activation of phospholipases linked with the inflammatory cascade, and thus supports, in part, lipolysis-driven inflammation within AT of periparturient cows.…”

“…Both enzymatic and nonenzymatic (FR mediated) oxidative reactions yield oxylipids that rapidly modulate inflammatory responses within AT. Remarkably, lipolysis significantly increases the content of oxylipids in the AT of healthy rodents and cows (Gartung et al, 2016;Contreras et al, 2020).…”