octadecadienoic-acid and Disease-Models--Animal

Conjugated linoleic acid (CLA) is composed of positional and stereoisomers of octadecadienoate (18:2); it is found in foods derived from ruminants (beef and lamb as well as dairy products from these sources). When a mixture of isomers is fed to experimental animals, chemically induced tumorigenesis of mammary, skin and colon is reduced. Importantly, many isomers of CLA are readily metabolized to desaturated/elongated products as well as beta-oxidized products, suggesting that these metabolites may be important anticancer compounds. Mechanisms of inhibition of carcinogenesis may include reduction of cell proliferation, alterations in the components of the cell cycle and induction of apoptosis. In addition, CLA modulates markers of immunity and eicosanoid formation in numerous species as well as lipid metabolism and gene expression. It is likely that CLA exerts inhibitory properties in carcinogenesis via one or more of these pathways with some tissue specificity. This review will explore recent advances in putative mechanisms of reduction of carcinogenesis by CLA.

Topics: Animals; Anticarcinogenic Agents; Apoptosis; Cell Division; Dairy Products; Disease Models, Animal; Eicosanoids; Fatty Acids, Unsaturated; Gene Expression Regulation, Neoplastic; Humans; Isomerism; Linoleic Acid; Lipid Metabolism; Meat; Neoplasms, Experimental; Ruminants

The human diet contains numerous endocrine-active compounds that influence mammalian physiology. The effects of these dietary compounds may be mediated by interaction with well-characterized intracellular hormone receptors or by other effects on patterns of endogenous hormone production, metabolism, target tissue signaling, growth, or differentiation. Because humans evolved as omnivores, the spectrum of dietary compounds that can be tolerated at modest levels of intake without frank toxicity is broad. Modest intake of these diverse nonnutritive endocrine-active compounds offers potential human health benefits through modulation of metabolic and hormonal responses, especially in sedentary individuals consuming a highly refined diet.

Topics: Animals; Diet; Disease Models, Animal; Endocrine System; Fatty Acids, Unsaturated; Food, Organic; Health; Humans; Isoflavones; Linoleic Acids; Neoplasms, Hormone-Dependent

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.

Topics: Amygdala; Animals; Chromatography, Liquid; Chronic Pain; Disease Models, Animal; Fatty Acids, Unsaturated; Inflammation; Male; Mice; Oxylipins; Periaqueductal Gray; Tandem Mass Spectrometry