Oxidized linoleic acid metabolites produced during lipolysis modulate adipose tissue.

During the periparturient period of dairy cows, adipose tissues (AT) lipolysis fulfills, in part, energy deficits driven by fetal growth and the onset of lactation. Lipolysis induces a remodeling process within AT that is characterized by a moderate inflammatory response with infiltration of macrophages. In periparturient cows that successfully transition into lactation, lipolysis rate decreases and AT inflammation resolves as lactation progresses.

However, when lipolysis rate is not reduced, AT inflammation is maintained leading to poor lactation performance. During lipolysis adipocytes produce hydroxyl-octadecadienoic acids (HODEs) from linoleic acid through enzymatic and non-enzymatic reactions. These lipolytic products are potent modulators of inflammatory responses in AT that may directly increase lipolysis rate by reducing adipocyte response to insulin. Our hypothesis is that lipolysis dysregulation increases AT abundance of HODEs, in a non- enzymatic, reactive oxygen species dependent manner, which enhances AT macrophage infiltration and sustains AT inflammation.

We will develop the hypothesis in two aims. Aim 1 will determine how HODEs synthesized during lipolysis in bovine AT modify macrophage phenotype and reduce the anti-lipolytic response of adipocytes to insulin. Aim 2 will determine the effect of lipolysis inhibition in periparturient dairy cows on non-enzymatic biosynthesis and profile of HODEs and AT macrophage phenotype. Upon completion of this project, we will be able to determine the role of HODEs in the vicious cycle of lipolysis dysregulation and chronic inflammation in AT. These findings will support their use as diagnostic, nutritional, or pharmacological targets in management programs of periparturient dairy cows.