This study demonstrates that a 4-week regimen of supplementation with AGE with and without exercise on body weight, fat accumulation, and inflammatory cytokines in HFD-induced obese rats. This result suggested that the major finding was that AGE supplementation showed anti-obesity effects; it attenuated the increase in body weight, visceral fat, liver weight, T-C, and LDL-C. Exercise with/without AGE supplementation also significantly improved obesity status, but the combination of exercise and AGE had an additive effect on body weight, visceral fat, and epididymal fat gain, as well as on TG levels.
High-energy diets are widely used to induce obesity and fat deposition in animals. Most studies found that HFD results in increased body weight, fat mass, and the development of hyperlipidemia and metabolic syndrome [28
]. We found that the HFD group had less food intake and a higher food efficiency ratio than the ND group. These findings indicate that the decrease in food intake was due to the increased amount of energy in the HFD, which has been reported previously [30
]. As expected, we found that the HFD significantly increased body weight and, fat mass, which led to obesity and hyperlipidemia [31
Exercise training is routinely suggested to prevent lifestyle-related diseases that are associated with obesity. It attenuates increase in body weight and visceral fat and reduces metabolic risk factors by increasing energy expenditure [32
]. In our HFD-induced obesity model, exercise significantly attenuated body weight and visceral fat increases observed during HFD consumption. These results indicate that increased physical activity was the main reason for reduced body fat accumulation. Our findings are similar to those of Gollisch et al. [7
], who demonstrated that exercise training led to reductions in body weight and visceral adipose tissue in rats. Similarly, we found that AGE supplementation also reduced the effect of HFD on weight and visceral fat gain. As expected, the combination of exercise and AGE supplementation was more effective than either intervention alone; the combined regimen attenuated the effect of the HFD on body and liver weight, as well as visceral and epididymal fat. Although the combined intervention group had the lowest liver weight, this result was not significantly different from the single interventions.
Food intake regulation, which may be modulated by neuroendocrine mechanisms, is an exceedingly complex biological process that involves a large number of cues and biological substrates [33
]. Energy expenditure by exercise and suppression of food intake may be related to altered appetite due to hypothalamic signals [34
]. In the present study, AGE supplementation and exercise either alone or as combined treatments significantly inhibited food intake. These interventions had a cumulative effect on reducing body weight, epididymal fat, liver weight, and TG levels. It is unclear whether AGE consumption directly changes appetite; therefore, this effect requires further investigation.
The exact mechanism by which increased adipose tissue mass induces metabolic dysfunction and atherogenic dyslipidemia is unclear. Adipose tissue lipolysis significantly promotes circulating fatty acids and is associated with hepatic steatosis [35
]. Our findings demonstrate that HFD significantly increased plasma TC, LDL-C, and TG levels in comparison with the ND. It is well known that increased plasma cholesterol increases the risk of developing atherosclerosis [37
]. Some studies have shown that exercise training inhibits the development of hepatic steatosis and reduces serum TG in obese rats [38
]. A previous study showed that garlic extract consumption attenuated serum TG in humans with high blood cholesterol [40
]. Surprisingly, exercise or AGE alone did not affect TG, but the combination of exercise with AGE supplementation attenuated HFD-induced hypertriglyceridemia. These results may indicate decreased TG levels were available for liver-induced lipid synthesis [41
], and insulin action in the liver was improved [42
] with Exercise+AGE. The present study demonstrates that AGE supplementation reduced T-C and LDL-C levels, effects that were not observed following Exercise or Exercise+AGE. This may be because AGE lower cholesterol in part by inhibiting hepatic cholesterol synthesis [43
Obesity leads to chronic low-grade inflammation that is associated with white adipose tissue, which produces and secretes a wide range of inflammatory molecules [44
]. Previous studies have demonstrated elevated IL-6 and TNF-α mRNA levels in obese subjects, which decrease following weight loss [45
]. Garlic extract has been shown to decrease IL-6 and TNF-α, suggesting an anti-inflammatory effect [46
]. In our study, we did not find any significant changes in IL-6, TNF-α, and CRP following HFD. However, exercise with and without AGE administration decreased plasma IL-6 levels, but the result was not statistically significant. Based on previous reports, we expected increased levels of pro-inflammatory cytokines levels with HFD [48
]. However, it is possible that a 10-week HFD regimen was not sufficient to elicit an appreciable increase. Although CRP was not significantly increased by HFD, exercise alone and in combination with AGE reduced CRP levels. These findings confirm the anti-inflammatory effect of exercise, and this effect was greater when AGE was not included in the regimen. Previous studies have been controversial, and some researchers reported that exercise training may decrease inflammatory cytokines [44
]. However, the anti-inflammatory mechanism of exercise training during HFD is unclear and requires further investigation.
In conclusion, this study demonstrated that AGE supplementation and exercise have beneficial effects on reducing weight and visceral fat gain in rats fed with HFD. AGE with and without exercise, but not exercise alone, effectively lowered blood lipids levels. In addition, AGE with exercise is more effective in controlling obesity and TG levels than either intervention alone. However, more extensive research is needed before recommending AGE supplementation to obese humans.