Whether PUFA diets affect inflammatory mediators in central and peripheral sites is not clear. We investigated the effect of high-fat PUFA diets on the expression of proteins involved in inflammatory pathways in hypothalamus, muscle, and liver. Male rats were fed for 2 months with either chow or high-fat diets enriched with either soy (n-6 PUFAs) or fish oil (n-3 PUFAs). The fish group had normal body weight, low serum NEFA, reduced hypothalamic levels of TNF-α, IL-6, and TRAF6, and increased levels of IL-10 receptor. In contrast, the soy group had increased body weight and hypothalamic levels of TRAF6 and NFκBp65. In muscle, the fish diet reduced TNF-α and IL-6 levels. Both PUFA diets increased muscle IL-10 levels and reduced liver TNF-α and IL-6 levels. The data showed that the high-fat soy diet induced activation of the hypothalamic NFκB inflammatory pathway, a feature predisposing to feeding and energy expenditure disturbances associated with the development of obesity. On the other hand, the high-fat fish diet improved the central and the peripheral inflammatory profile via reduction of intracellular inflammatory mediators, suggesting a protection against obesity. 1. Introduction Obesity is known to present an inflammatory process of low grade, with elevated levels of cytokines such as interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), and interleukin 1 beta (IL-1β), contributing to the pathogenesis of important disturbances of the obese condition, as insulin resistance and metabolic defects. This inflammatory state has been described to induce elevated signaling through the toll-like receptors TLR2 and TLR4, with activation of the nuclear factor κB (NFκB) pathway in muscle, liver, and adipose tissue [1–4]. In this inflammatory pathway, TLR2/4 binding to the myeloid differentiation factor-88 (MyD88) leads, after some intermediate steps, to the recruitment of the tumor necrosis factor receptor-associated factor-6 (TRAF6). Its interactions with several proteins leads to phosphorylation of the inhibitory factor IκB, which is then targeted for proteosomal degradation, releasing NFκB, whose p65 subunit undergoes phosphorylation and translocates to the nucleus, where it binds to its target genes to produce proinflammatory cytokines [5]. Importantly, prolonged intake of saturated or trans fats has also been associated with NFκB/MyD88 pathway-mediated induction of inflammatory cytokines in the hypothalamus and cytokine-induced impairment of central insulin hypophagia [6–10]. The hypothalamus is a key regulator of energy homeostasis, through the
References
[1]
D. M. L. Tsukumo, M. A. Carvalho-Filho, J. B. C. Carvalheira et al., “Loss-of-function mutation in toll-like receptor 4 prevents diet-induced obesity and insulin resistance,” Diabetes, vol. 56, no. 8, pp. 1986–1998, 2007.
[2]
S. Schenk, M. Saberi, and J. M. Olefsky, “Insulin sensitivity: modulation by nutrients and inflammation,” Journal of Clinical Investigation, vol. 118, no. 9, pp. 2992–3002, 2008.
[3]
C. M. O. Nascimento, E. B. Ribeiro, and L. M. Oyama, “Metabolism and secretory function of white adipose tissue: effect of dietary fat,” Anais da Academia Brasileira de Ciências, vol. 81, pp. 453–466, 2010.
[4]
R. G. Baker, M. S. Hayden, and S. Ghosh, “NF-κB, inflammation, and metabolic disease,” Cell Metabolism, vol. 13, no. 1, pp. 11–22, 2011.
[5]
S. Akira, “Toll-like receptor signaling,” Journal of Biological Chemistry, vol. 278, no. 40, pp. 38105–38108, 2003.
[6]
M. Milanski, G. Degasperi, A. Coope et al., “Saturated fatty acids produce an inflammatory response predominantly through the activation of TLR4 signaling in hypothalamus: implications for the pathogenesis of obesity,” Journal of Neuroscience, vol. 29, no. 2, pp. 359–370, 2009.
[7]
K. A. Posey, D. J. Clegg, R. L. Printz et al., “Hypothalamic proinflammatory lipid accumulation, inflammation, and insulin resistance in rats fed a high-fat diet,” American Journal of Physiology, vol. 296, no. 5, pp. E1003–E1012, 2009.
[8]
E. P. Araújo, M. A. Torsoni, and L. A. Velloso, “Hypothalamic inflammation and obesity,” Vitamins and Hormones, vol. 82, pp. 129–143, 2010.
[9]
G. D. Pimentel, F. S. Lira, J. C. Rosa, et al., “Intake of trans fatty acids during gestation and lactation leads to hypothalamic inflammation via TLR4/NFkappaBp65 signaling in adult offspring,” Journal of Nutritional Biochemistry, vol. 23, pp. 822–828, 2012.
[10]
X. Wang, X. Zhou, L. Liu, et al., “Increased hypothalamic inflammation associated with the susceptibility to obesity in rats exposed to high-fat diet,” Experimental Diabetes Research, vol. 2012, pp. 1–8, 2012.
[11]
J. B. C. Carvalheira, E. B. Ribeiro, R. B. Guimar？es, et al., “Selective impairment of insulin signalling in the hypothalamus of obese Zucker rats,” Diabetologia, vol. 46, pp. 1629–1640, 2003.
[12]
K. T. Albuquerque, F. L. C. Sardinha, M. M. Telles et al., “Intake of trans fatty acid-rich hydrogenated fat during pregnancy and lactation inhibits the hypophagic effect of central insulin in the adult offspring,” Nutrition, vol. 22, no. 7-8, pp. 820–829, 2006.
[13]
F. L. C. Sardinha, M. M. Telles, K. T. Albuquerque et al., “Gender difference in the effect of intrauterine malnutrition on the central anorexigenic action of insulin in adult rats,” Nutrition, vol. 22, no. 11-12, pp. 1152–1161, 2006.
[14]
E. B. Ribeiro, “Studying the central control of food intake and obesity in rats,” Brazilian Journal of Nutrition, vol. 22, no. 1, pp. 163–171, 2009.
[15]
E. B. Ribeiro, M. M. Telles, L. M. Oyama, et al., “Hypothalamic serotonin in the control of food intake: physiological interactions and effect of obesity,” in Focus on Nutrition Research, T. P. Starks, Ed., pp. 121–148, Nova Science Publishers, New York, NY, USA, 2006.
[16]
R. L. H. Watanabe, I. S. Andrade, J. C. S. Zemdegs et al., “Prolonged consumption of soy or fish-oil-enriched diets differentially affects the pattern of hypothalamic neuronal activation induced by refeeding in rats,” Nutritional Neuroscience, vol. 12, no. 6, pp. 242–248, 2009.
[17]
R. L. H. Watanabe, I. S. Andrade, M. M. Telles et al., “Long-term consumption of fish oil-enriched diet impairs serotonin hypophagia in rats,” Cellular and Molecular Neurobiology, vol. 30, no. 7, pp. 1025–1033, 2010.
[18]
G. D. Pimentel, A. P. S. Dornellas, J. C. Rosa et al., “High-fat diets rich in soy or fish oil distinctly alter hypothalamic insulin signaling in rats,” Journal of Nutritional Biochemistry, vol. 23, pp. 265–271, 2012.
[19]
X. Zhang, G. Zhang, H. Zhang, et al., “Hypothalamic IKK /NF- B and ER stress link overnutrition to energy imbalance and obesity,” Cell, vol. 135, pp. 61–73, 2008.
[20]
D. E. Cintra, E. R. Ropelle, J. C. Moraes et al., “Unsaturated fatty acids revert diet-induced hypothalamic inflammation in obesity,” PLoS ONE, vol. 7, no. 1, article e30571, 2012.
[21]
D. Y. Oh and J. M. Olefsky, “Omega 3 fatty acids and GPR120,” Cell Metabolism, vol. 15, no. 5, pp. 564–565, 2012.
[22]
Y. Y. Lam, G. Hatzinikolas, J. M. Weir, et al., “Insulin-stimulated glucose uptake and pathways regulating energy metabolism in skeletal muscle cells: the effects of subcutaneous and visceral fat, and long-chain saturated, and polyunsaturated fatty acids,” Biochimica et Biophysica Acta, vol. 1811, pp. 468–475, 2011.
[23]
D. Moertl, A. Hammer, S. Steiner, R. Hutuleac, K. Vonbank, and R. Berger, “Dose-dependent effects of omega-3-polyunsaturated fatty acids on systolic left ventricular function, endothelial function, and markers of inflammation in chronic heart failure of nonischemic origin: a double-blind, placebo-controlled, 3-arm study,” American Heart Journal, vol. 161, no. 5, pp. 915.e1–915.e9, 2011.
[24]
S. C. Cottin, T. A. Sanders, and W. L. Hall, “The differential effects of EPA and DHA on cardiovascular risk factors,” Proceedings of the Nutrition Society, vol. 70, no. 2, pp. 215–231, 2011.
[25]
C. D. Byrne, “Fatty liver: role of inflammation and fatty acid nutrition,” Prostaglandins Leukotrienes and Essential Fatty Acids, vol. 82, no. 4-6, pp. 265–271, 2010.
