Several 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. Protein 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. Our data suggest that the pro-apoptotic effect of FO in Walker 256 tumor is related with specifics cleaved caspases.

Obesity 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. Monosodium 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. Obese 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. Low 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.

Shark liver oil (SLOil) and fish oil (FOil), which are respectively rich in alkylglycerols (AKGs) and n-3 polyunsaturated fatty acids (PUFAs), are able to reduce the growth of some tumors and the burden of cachexia. It is known that FOil is able to reduce proliferation rate and increase apoptotic cells and lipid peroxidation of tumor cells efficiently. However, there are few reports revealing the influence of SLOil on these parameters. In the current study, effects of FOil chronic supplementation on tumor growth and cachexia were taken as reference to compare the results obtained with SLOil supplementation. Also, we evaluated if the association of SLOil and FOil was able to promote additive effects. Weanling male Wistar rats were divided into 4 groups: fed regular chow (C), supplemented (1 g/kg body weight) with SLOil (CSLO), FOil (CFO) and both (CSLO + FO). After 8 weeks half of each group was inoculated with Walker 256 cells originating new groups (W, WSLO, WFO and WSLO + FO). Biochemical parameters of cachexia, tumor weight, hydroperoxide content, proliferation rate and percentage of apoptotic tumor cells were analysed. Fatty acids and AKG composition of tumor and oils were obtained by high performance liquid chromatography and gas chromatography – mass spectrometry, respectively. Statistical analysis was performed by unpaired t-test and one-way ANOVA followed by a post hoc Tukey test. Fourteen days after inoculation, SLOil was able to restore cachexia parameters to control levels, similarly to FOil. WSLO rats presented significantly lower tumor weight (40%), greater tumor cell apoptosis (~3-fold), decreased tumor cell proliferation (35%), and higher tumor content of lipid hydroperoxides (40%) than observed in W rats, but FOil showed more potent effects. Supplementation with SLOil + FOil did not promote additive effects. Additionally, chromatographic results suggested a potential incorporation competition between the n-3 fatty acids and the AKGs in the tumor cells’ membranes. SLOil is another marine source of lipids with similar FOil anti-cachectic capacity. Furthermore, despite being less potent than FOil, SLOil presented significant in vivo antitumor effects. These results suggest that the chronic supplementation with SLOil may be adjuvant of the anti-cancer therapy.

Glucocorticoid (GC) excess alters glucose homeostasis and promotes modifications in murinometric and anthropometric parameters in rodents and humans, respectively. β-hydroxy-β-methylbutyrate (HMB), a leucine metabolite, has been proposed as a nutritional strategy for preventing muscle wasting, but few data regarding its effects on glucose homeostasis are available. Here, we analyzed whether the effects of GC excess on glucose homeostasis may be attenuated or exacerbated by the concomitant ingestion of HMB. Adult Wistar rats (90-days-old) were assigned to four groups: (1) vehicle treated (Ctl), (2) dexamethasone (DEX) treated (Dex), (3) HMB treated (Hmb), and (4) DEX plus HMB treated (DexHmb). Dex groups received DEX (1 mg·kg body weight (BW)⁻¹, intraperitoneal) for 5 consecutive days. HMB groups ingested HMB (320 mg·kg BW⁻¹, oral gavage) for the same 5 days. HMB ingestion did not attenuate the effects of DEX on food intake and body weight loss, changes in masses of several organs, insulin resistance, and glucose intolerance (p > 0.05). In fact, in DexHmb rats, there was increased fasting glycemia and exacerbated glucose intolerance with the main effect attributed to DEX treatment (p < 0.05). HMB exerted no attenuating effect on plasma triacylglycerol levels from DexHmb rats, but it seems to attenuate the lipolysis induced by β-adrenergic stimulation (20 μmol·L⁻¹isoproterenol) in fragments of retroperitoneal adipose tissue from DexHmb rats. Therefore, HMB does not attenuate the diabetogenic characteristics of GC excess. In fact, the data suggest that HMB may exacerbate GC-induced glucose intolerance.