Linoleic acid derived oxylipins are elevated in kidney and liver and reduced in serum in rats given a high-protein diet

Abstract

High protein (HP) diets are often used as a means to reduce obesity, but their long-term effects remain unclear. In vitro studies suggest the involvement of a subset of oxylipins in the tissue response to HP diets. To examine the role of these bioactive lipids in vivo, normal adult male Sprague Dawley rats were provided isocaloric diets with LP (low protein, 8% protein by weight), NP (normal protein, 14%) or HP (50%) diets for 2 weeks, and targeted lipidomic analysis of oxylipins in kidney (cortex and medulla), liver and serum was performed by HPLC-MS/MS. The main group of oxylipins affected by the HP diet was the oxylipins derived from linoleic acid (LA), many of which were elevated in kidney (particularly the medulla) and liver, but reduced in serum of rats provided the HP compared to NP or LP diets. A smaller proportion of other n-6 fatty acid derived oxylipins were lower in kidney and higher in liver, and none were affected in serum, by HP feeding. Few n-3 oxylipins were affected by protein level. In liver only, the oxylipin product to substrate ratios of the soluble epoxide hydrolase enzyme were higher in LP fed rats. Differences between cortex and medulla oxylipins suggest relatively higher cortex activity of 5- and 8-lipoxygenase and cytochrome P450 hydroxylase, and higher medulla cyclooxygenase and 12- and 15-lipoxygenase activity. Further studies are needed to elucidate the physiological effects of the changes in these novel oxylipins in response to short-term dietary HP.