The obese animals presented higher Lee index and increase of fat depots (Table ). These results confirm the obesity induction by glutamate monosodium and corroborate previous studies [14
]. Several metabolic changes of this model occur due to hypothalamic lesions, mainly on the arcuate nucleus [16
]. These lesions result in impaired insulin signaling and reduction of GHRH (Growth Hormone Releasing Hormone), which is associated with body length reduction also related to reduction of body weight (Table ). This model also presents reduction of sympathetic activity and low HSL (Hormone Senstive Lipase) activity which is an enzyme with a role in the triacyglycerol hydrolysis [17
]. These alterations in adipose tissue metabolism may explain the high quantities found in epididymal and retroperitoneal adipose tissues (Table ). Thus, the MSG rats have been used for studies of obesity because they usually present insulin resistance and high depots of fat [17
]. Interestingly, there are no reports on employing this model to examine the effects of fish oil supplementation.
Rats fed under an isocaloric high fat diet plus 7% of fish oil showed improved insulin sensitivity quantified by euglycemic-hyperinsulinemic glucose clamp [22
]. Andersen and coworkers showed reduction of glycemy and improved insulin sensitivity by HOMA test after oral supplementation of EPA or DHA (0.5 g/kg) for 8 weeks [12
]. Our study corroborates these previous finding, showing the ability of fish oil supplementation to improve insulin sensitivity in obese animals. In contrast, Gillam and coworkers did not find any effect of the fish oil (10%) added to diet on insulin resistance, pancreatic function and glucose metabolism [23
]. The discrepancy between these results may be due the concentration of fish oil added to diet and models used, i.e., high fat and/or high-sucrose diets to induce obesity, or genetically obesity models.
Dyslipidaemia is a common feature in diabetic people and it is strongly associated with the development of atherosclerosis [24
]. The MSG rats presented higher levels of TG and cholesterol, as previously described [21
]. Lipoproteins rich in TG play a role in inflammatory process through NF-κB activation [25
]. Thus, the reduction of TG levels found within this study and others [26
] is an important factor which might explain part of the beneficial effects of n-3 fatty acids on cardiovascular diseases. Hypercholesterolemia increases the expression of adhesion molecules involved in atherogenesis [28
]. Our study also showed the ability of fish oil to reduce cholesterol levels of obese rats.
Skeletal muscle is the principal site of glucose metabolism and represents 40 to 50% of the total body mass. Nevertheless, to best of our knowledge, there is no report about the changes on muscle metabolism of the MSG rats. Analyzing the results from muscle metabolism responses and comparing them to systemic insulin resistance, data might seem paradoxal. There are possible reasons for these findings. First, the results from systemic insulin resistance may be influenced by several factors, besides the muscle, such as free fatty acids [29
], cytokines [30
] and other insulin targets like adipose tissue and liver [31
]. Second, a state of hyperinsulinemia usually found in this model could result in the increase of cell metabolism for a short period [32
]. D'Alessandro and coworkers showed that fed rats with a diet plus 7% fish oil increased insulin sensitivity of skeletal muscle [33
]. This study also found that under insulin stimuli, the glycolytic pathway was more activated rather than oxidation and storage components of glucose metabolism. This result differs from the data herein reported, probably owing to different deployed methodologies i.e. muscle type and enzymes analyzed. Interestingly, our study is the first to report these effects using a lower dose (1 g/kg/day) orally administrated on obese rats induced by MSG.