Effects of fish oil on hypertension, plasma lipids, and tumor necrosis factor- in rats with sucrose-induced metabolic syndrome Alfonso Alexander Aguilera, Guillermo Herna ´ndez Dı ´az, Martı ´n Lara Barcelata, Ofelia Angulo Guerrero, Rosa M. Oliart Ros* Instituto Tecnolo ´gico de Veracruz, UNIDA, Apdo. Postal 1420, Veracruz, Ver. Me ´xico Received 21 May 2003; received in revised form 18 November 2003; accepted 23 December 2003 Abstract Dietary fish oil rich in (n-3) fatty acids plays an important role in reducing abnormalities associated with the metabolic syndrome and mortality from coronary heart disease. We investigated the effects of dietary fish oil on the metabolic syndrome in a high-sucrose–fed rat model. The model was achieved by the administration of 30% sucrose in drinking water in male Wistar rats during 21 weeks. After the metabolic syndrome rat model was established, fish oil was administered during 6 weeks. The metabolic syndrome rats showed significant increases in body weight, systolic blood pressure, serum insulin, total lipids, triacylglycerols, cholesterol, free fatty acids, LDL, total proteins, albumin, and serum tumor necrosis factor– (TNF-). They also presented abdominal and epididymal fat accumulation and fatty liver. After fish oil diet administration, metabolic syndrome rats had a significant reduction in blood pressure, serum insulin, triacylglycerols, cholesterol, free fatty acids, and total lipids, but no change was observed in TNF- concentration or fat accumulation. In conclusion, fish oil reversed the alterations on metabolic parameters and blood pressure exerted by sucrose administration, although it had no effect on TNF- production and adiposity. This confirms the theory that the molecular etiology of the metabolic syndrome is multifactorial, as is the effect of n-3 polyunsaturated fatty acids (PUFAs) upon it, having complex and multifaceted actions. © 2004 Elsevier Inc. All rights reserved. Keywords: Fish oil; Metabolic syndrome; Sucrose-induced model; TNF- 1. Introduction In 1988, Gerald Reaven introduced the concept of “syn- drome X” for the clustering of cardiovascular risk factors such as hypertension, glucose intolerance, high triacylglyc- erols, and low HDL cholesterol concentrations found in individuals prone to develop cardiovascular diseases (CVD), and proposed that the common denominator of the syndrome was resistance to the action of insulin [1]; other metabolic abnormalities have been associated with this syn- drome, including obesity, microalbuminuria, alterations in fibrinolysis, and coagulation [2,3]. The syndrome has also been called insulin resistance syndrome, cardiovascular syndrome, and more recently metabolic syndrome. Recent studies have suggested that inflammatory mediators such as tumor necrosis factor- (TNF-) and interleukins (ILs) play a central role in the development of cardiovascular diseases. Elevated plasma levels of TNF- have been found to be associated with obesity, insulin resistance, hypertriglyceri- demia, and glucose intolerance [4]. CVDs have become the leading cause of morbidity and mortality in western countries [5], totaling 22.43% of all deaths in Mexico in 2002 [6]. CVDs are one of the signif- icant diet-related health problems; there are a number of epidemiological studies supporting the dietary regulation of each of the metabolic risk factors of metabolic syndrome [7–10], and there is a great deal of interest in how dietary fat composition influences the development of this syndrome. Long-chain (n-3) polyunsaturated fatty acids have attracted considerable attention for the last few years, as dietary fish oil rich in EPA (20:5 n-3) and DHA (22:6 n-3) fatty acids plays an important role in reducing hypertriglyceridemia and seems to lower mortality from coronary heart disease [11–13]. It is important to note, however, that discrepancies exist regarding differences in the effects on metabolic syn- drome parameters after fish oil or n-3 fatty acid administra- tion, as well as in the mechanisms proposed to explain such effects. * Corresponding author. Tel.: 52 (229) 9 34 57 01 ext 112; fax: 52 (229) 9 34 57 01 ext 201. E-mail address: roliart@itver.edu.mx (R.M. Oliart Ros). Journal of Nutritional Biochemistry 15 (2004) 350 –357 0955-2863/04/$ – see front matter © 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.jnutbio.2003.12.008