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In this study we investigated the effect of lifelong supplementation of the diet with coconut oil (CO, rich in saturated fatty acids) or fish oil (FO, rich in n-3 polyunsaturated fatty acids, PUFAs) on tumor growth, animal survival, and metabolic indicators of cachexia in adult rats. Female Wistar rats were supplemented with CO or FO prior to mating and then throughout pregnancy and gestation, and then the male offspring were supplemented from weaning until 90 days of age. Then they were inoculated subcutaneously with Walker 256 tumor cells. Tumor weight at 14 days in control rats (those fed standard chow) was approximately 20 g. These animals displayed cancer cachexia, which was characterized by loss of weight, hypoglycemia, hyperlacticidemia, hypertriacylglycerolemia, and depletion of glycogen stores. Supplementation of the diet with CO did not change these parameters, except that there was a smaller decrease in serum triacylglycerol concentration. Supplementation of the diet with FO significantly decreased tumor growth (by approximately 60%), increased survival (50% at 30 days postinoculation vs. 30% in the controls and 13.5% in the CO group), and prevented the fall in body weight. Furthermore, FO supplementation partly abolished the fall in serum glucose, totally prevented the elevation in serum lactate concentrations, partly prevented the hypertriacylgylcerolemia, and preserved tissue glycogen stores. Lifelong consumption of FO, rich in n-3 PUFAs, protects against tumor growth and cancer cachexia and improves survival.

BackgroundObesity is commonly associated with diabetes, cardiovascular diseases and cancer. The purpose of this study was to determinate the effect of a lower dose of fish oil supplementation on insulin sensitivity, lipid profile, and muscle metabolism in obese rats.MethodsMonosodium glutamate (MSG) (4 mg/g body weight) was injected in neonatal Wistar male rats. Three-month-old rats were divided in normal-weight control group (C), coconut fat-treated normal weight group (CO), fish oil-treated normal weight group (FO), obese control group (Ob), coconut fat-treated obese group (ObCO) and fish oil-treated obese group (ObFO). Obese insulin-resistant rats were supplemented with fish oil or coconut fat (1 g/kg/day) for 4 weeks. Insulin sensitivity, fasting blood biochemicals parameters, and skeletal muscle glucose metabolism were analyzed.ResultsObese animals (Ob) presented higher Index Lee and 2.5 fold epididymal and retroperitoneal adipose tissue than C. Insulin sensitivity test (Kitt) showed that fish oil supplementation was able to maintain insulin sensitivity of obese rats (ObFO) similar to C. There were no changes in glucose and HDL-cholesterol levels amongst groups. Yet, ObFO revealed lower levels of total cholesterol (TC; 30%) and triacylglycerol (TG; 33%) compared to Ob. Finally, since exposed to insulin, ObFO skeletal muscle revealed an increase of 10% in lactate production, 38% in glycogen synthesis and 39% in oxidation of glucose compared to Ob.ConclusionsLow dose of fish oil supplementation (1 g/kg/day) was able to reduce TC and TG levels, in addition to improved systemic and muscle insulin sensitivity. These results lend credence to the benefits of n-3 fatty acids upon the deleterious effects of insulin resistance mechanisms.

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In this study we investigate the impact of the dietary ratio of n-6 to n-3 fatty acids (FAs) from postweaning until adult age upon tumor growth, lipid peroxidation in tumor tissue, and metabolic indicators of cancer cachexia in Walker 256 tumor-bearing rats. Weanling male Wistar rats received a normal low-fat (40 g/kg diet) chow diet or high-fat diets (300 g/kg) that included fish oil (FO) or sunflower oil or blends of FO and sunflower oil to yield n-6 to n-3 FA ratios of approximately 6:1, 30:1, and 60:1 ad libitum. After 8 wk, half of each group was inoculated with 1 ml of 2 x 10(7) Walker 256 cells. At the 14th day after tumor inoculation, the animals were killed, and tumors and blood were removed. The different diets did not modify the blood parameters in the absence of tumor bearing, except the high-FO diet, which decreased serum cholesterol and triacylglycerol concentrations. Tumor weight in chow-fed rats was 19 g, and these rats displayed cancer cachexia, characterized by hypoglycemia, hyperlacticidemia, hypertriacylglycerolemia, loss of body weight, and food intake reduction. Tumor weight in FO-fed rats was 7.7 g, and these animals gained body weight (14.6 g) and maintained blood metabolic parameters similar to non-tumor-bearing animals. Tumor weight in rats fed the diet with an n-6 to n-3 FA ratio of 6:1 was similar to tumor-bearing, chow-fed rats, but they gained 2 g in the body weight and blood metabolic parameters were similar to those in non-tumor-bearing rats. However, a further increase in the n-6 FA content of the diet did not change the cachectic state associated with tumor bearing. In this experimental model, a dietary n-6 to n-3 FA ratio of 6:1 was able to increase food intake and body weight, restore the biochemical blood parameters of cachexia, and prevent the development of cancer cachexia.

Background/Objectives: Glutamine plays a key role in immune response. Spinal cord injury (SCI) leads to severe loss of muscle mass and to a high incidence of infections. This study investigated the acute effect of SCI (2 and 5 days) on the plasma glutamine and skeletal muscle concentrations and immune responses in rats. Methods: A total of 29 adult male Wistar rats were divided as follows: control (C; n ¼ 5), sham-operated (S2; n ¼ 5) and spinal cord-transected (T2; n ¼ 7). They were killed on day 2 after surgery/transection (acute phase). Another set was sham-operated (S5; n ¼ 5), spinal cord-transected (T5; n ¼ 7), and killed at day 5 after surgery/transection (secondary phase). Blood was collected; the white portion of the epitrochlearis and gastrocnemius muscles and the red portion of soleus muscles were dissected to measure the glutamine concentration. Gut-associated lymphocytes and peritoneal macrophages were obtained for immune parameters measurements. Results: Glutamine concentration in the plasma, gastrocnemius, and soleus muscles in rats with SCI were significantly reduced but not in the epitrochlearis muscle in the acute (2 days) and secondary (5 days) phases. Phagocytic response was reduced in the acute phase but increased in the secondary phase in rats with SCI. Superoxide production, on the other hand, was significantly increased at days 2 and 5 after SCI, and CD8 þ lymphocytes subset decreased significantly on days 2 and 5. Conclusions: Our results showed reduction in plasma glutamine and skeletal muscle concentrations after spinal cord transection. They also suggest that SCI and glutamine reduction contribute to an alteration in immune competence.

BackgroundSeveral studies have been shown pro-apoptotic effects of fish oil (FO), rich in n-3 polyunsaturated fatty acids (n-3 PUFA) on cancer cells. Nevertheless, few in vivo experiments have provided data of its ability on apoptosis protein expression in tumor tissue. Thus, in this study we investigate the effect of FO supplementation on apoptosis protein expression in Walker 256 tumor bearing rats. Male Wistar rats were randomly assigned to three groups: fed with regular chow (W); fed regular chow supplemented with FO (WFO) or coconut fat (WCO) (1 g/kg body weight/daily). After thirty days, all animals were inoculated subcutaneously with Walker 256 tumor cells.FindingsProtein expression was done by western blotting in Walker 256 tumor tissue samples. FO decreased the Bcl-2/Bax ratio (p < 0.05) and increased the p53 (p < 0.05), cleaved caspase-7 (p < 0.05) and cleaved caspase-3 (p < 0.05) in Walker 256 tumor tissue.ConclusionsOur data suggest that the pro-apoptotic effect of FO in Walker 256 tumor is related with specifics cleaved caspases.

The effect of coconut fat (rich in medium saturated fatty acids) or fish oil (rich in x-3 polyunsaturated fatty acids) supplementation for 2 generations on tumor growth, cancer cachexia, animal survival and macrophage function was investigated in Walker 256 tumor-bearing rats. Female Wistar rats were supplemented with coconut fat or fish oil prior to mating and then throughout pregnancy and gestation. Both supplementations were daily and orally given at 1 g per kg body weight as a single bolus. Same treatment was performed by the 2 following generations. At 90 days of age, male offspring (50%) from F2 generation were subcutaneously inoculated with 2 3 10 7 Walker 256 tumor cells. At 14 days after tumor implantation, rats not supplemented displayed cancer cachexia characterized by loss of body weight, hypoglycemia, hyperlacticidemia, hypertriglyceridemia, decreased food intake and depletion of glycogen stores in the liver and skeletal muscles. Supplementation with coconut fat did not affect these parameters. However, supplementation with fish oil decreased tumor growth (59%), prevented body weight loss and food intake reduction and attenuated cancer cachexia. In addition, fish oil increased animal survival up to 20 days (from 25% in rats not supplemented to 67% in rats supplemented with fish oil) and improved macrophage function characterized by increased phagocytosis capacity and production of hydrogen peroxide and nitric oxide. These results suggest that fish oil supplementation for 2 generations improves macrophage function in association to reduced tumor growth and attenuated cancer cachexia, maintaining food intake and increasing animal survival. ' 2006 Wiley-Liss, Inc.Key words: fish oil; macrophage function; tumor growth; cancer cachexia; x-3 polyunsaturated fatty acids Cancer cachexia syndrome is characterized by body weight loss, asthenia, weakness, anemia, edema, increased hepatic gluconeogenesis and resting energy expenditure, intense catabolism of carbohydrate, lipid and protein stores 1-4 and anorexia. 5 This debilitating condition leads to death of up to 70% of patients with cancer. 6,7 Moreover, deaths by secondary infections due to impairment of immune function are frequent in patients with cancer cachexia. 2 In fact, cachexia is considered the major complication to treat cancer patients. 8 Current diet of the Western world has a high content of saturated fatty acids and x-6 polyunsaturated fatty acids (x-6 PUFA) and low content of x-3 PUFA. 9 This fat dietary composition has been correlated with increased occurrence of certain neoplasias such as colon, colorectal, breast and prostate cancers. 10-14 Epidemiological and experimental studies have shown that x-3 PUFA, mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), present anticancer effects 15-21 and improve action of other anticancer agents. [22][23][24] Greenland Eskimos and Alaskans that consume large quantity of x-3 PUFA from fish oil present a lower colon cancer risk than North Americans that consume a low quantity of x-3 PU...