Concentrations of oxidized linoleic acid derived lipid mediators in the amygdala and periaqueductal grey are reduced in a mouse model of chronic inflammatory pain.

Chronic pain is both a global public health concern and a serious source of personal suffering for which current treatments have limited efficacy. Recently, oxylipins derived from linoleic acid (LA), the most abundantly consumed polyunsaturated fatty acid in the modern diet, have been implicated as mediators of pain in the periphery and spinal cord. However, oxidized linoleic acid derived mediators (OXLAMs) remain understudied in the brain, particularly during pain states. In this study, we employed a mouse model of chronic inflammatory pain followed by a targeted lipidomic analysis of the animals' amygdala and periaqueductal grey (PAG) using LC-MS/MS to investigate the effect of chronic inflammatory pain on oxylipin concentrations in these two brain nuclei known to participate in pain sensation and perception. From punch biopsies of these brain nuclei, we detected twelve OXLAMs in both the PAG and amygdala and one arachidonic acid derived mediator, 15-HETE, in the amygdala only. In the amygdala, we observed an overall decrease in the concentration of the majority of OXLAMs detected, while in the PAG the concentrations of only the epoxide LA derived mediators, 9,10-EpOME and 12,13-EpOME, and one trihydroxy LA derived mediator, 9,10,11-TriHOME, were reduced. This data provides the first evidence that OXLAM concentrations in the brain are affected by chronic pain, suggesting that OXLAMs may be relevant to pain signaling and adaptation to chronic pain in pain circuits in the brain and that the current view of OXLAMs in nociception derived from studies in the periphery is incomplete.

A comparison of effects of lard and hydrogenated vegetable shortening on the development of high-fat diet-induced obesity in rats.

BACKGROUND: Obesity is associated with increased consumption and preference for dietary fat. Experimental models of fat-induced obesity use either lard or vegetable shortening. Yet, there are no direct comparisons of these commonly used fat sources, or the influence of their fatty acid composition, on the development of diet-induced obesity. OBJECTIVE: To compare the effects of lard and hydrogenated vegetable-shortening diets, which differ in their fatty acid composition, on weight gain and the development of obesity and insulin resistance in rats. METHODS AND DESIGN: Male Wistar rats were fed ad libitum for 14 weeks high-fat diets containing either (1) high vegetable fat (HVF, 60 kcal% from vegetable shortening) or (2) high lard fat (HLF, 60 kcal% from lard). Rats fed normal-fat (NF, 16 kcal% from vegetable shortening) diet served as control. Body weight, food intake, adipose tissue mass, serum 25[OH]D3, glucose, insulin and fatty acid composition of diets were measured. RESULTS: Rats fed either of the two high-fat diets had higher energy intake, weight gain and fat accretion than rats fed normal-fat diet. However, rats fed the HLF diet consumed more calories and gained more weight and body fat with greater increases of 32% in total (158.5±8.2 vs 120.2±6.6 g, P<0.05), 30% in visceral (104.4±5.2 vs 80.3±4.2 g, P<0.05) and 36% in subcutaneous fat mass (54.1±3.6 vs 39.9±3.1 g, P<0.05), compared with rats fed the HVF diet. Higher visceral adiposity was positively correlated with serum insulin (r=0.376, P<0.05) and homeostatic model assessment insulin resistance (r=0.391, P<0.05). CONCLUSION: We conclude that lard-based high-fat diets accentuate the increase in weight gain and the development of obesity and insulin resistance more than hydrogenated vegetable-shortening diets. These results further point to the importance of standardizing fatty acid composition and type of fat used in determining outcomes of consuming high-fat diets.