## 4 Discussion
Therefore, lower FER in the F2-treated group might be due to an interfering with the pancreatic lipase causing reduced dietary fat absorption. The extent of weight gain in 7-weeks of drug treatment was significantly lower than that in 5-weeks of the obesity induction period (Figure 5). These findings reinforced the FER and weight gain reducing effect of F2 observed in the previous study [22]. an inflammatory cytokine, IL-6, was found to be under-expressed in WAT, indicating the formulation F2 has a positive response in ameliorating obesity-associated inflammatory responses. The secretion of IL-6 and TNFx by adipose tissue in obesity leads to chronic inflammation, and so promotes insulin resistance [28; 44]. In the previous report, we showed that the gene expression level of the aforementioned adipogenic transcription factors is down-regulated in F2 treated 3T3-L1 adipocytes [22]. From all the observations, it may be suggested that the anti-obesity action of F2 might be due to the restriction of adipogenesis in adipose tissue. It is well known that the \(\beta\) cells of pancreatic islets secret insulin to maintain the basal level of blood glucose. In normal conditions, the \(\beta\) cell function and population dynamics are influenced by the blood glucose concentration [45]. Insulin travels through the body and induces muscles and fat cells to absorb glucose. In addition, insulin selectively induces glycogenesis when postprandial blood glucose levels become elevated. Once the blood glucose level returns to its basal level, insulin secretion is also adapted [46]. When the body systems are exposed to high fat for a long time, it may cause an impairment on insulin binding to its receptors and/or glucose transporter in muscle and fat cells, resulting in decreased insulin sensitivity [47]. As a result, pancreatic \(\beta\) cells secret more insulin to cope with peripheral insulin resistance in muscle and adipose tissue to maintain the normal level of blood glucose. This condition has been termed as compensatory hyperinsulinemia [45]. The previous literature has also revealed that dietary high-fat leads to promote insulin resistance and hyperinsulinemia before the development of type 2 diabetes in rodents [48; 49; 50]. High-fat diet-induced hyperinsulinemia or insulin resistance may occur due to a decrease in the glucose transporter, insulin receptors, and glucose metabolism [10; 28]. The systemic insulin resistance was quantified in the term of the HOMA-IR index [25]. In the current study, the serum insulin level was found to be drastically increased in the HFD control group. However, in F2 and GC-treated groups, the insulin level was significantly diminished (Table 5). However, the blood glucose level was not altered among the groups. These observations indicated that the mice were developing compensatory hyperinsulinemia in the HFD control group as a result of partial insulin resistance. F2 and GC were found to ameliorate HFD-induced insulin resistance. In contrast with the observations of the current experiment, the blood glucose level was significantly reduced by F2 compared to the HFD control in the previous study [22]. These findings indicated that the formulation F2 could have preventive effect in controlling the blood glucose level. In other words, seven weeks treatment of F2 in obese mice was effective enough for protection against insulin resistance. Therefore, it may be suggested that the F2 might be effective in reducing the blood glucose level in obese mice if the treatment period would be longer. The effect of F2 on the weight of visceral organs of obese mice and their histological evaluations were analyzed in the current study following a similar procedure as in the previous study [22]. Similar results were found in both studies that the weights of the WAT in the HFD control group were significantly increased due to the over deposition of lipids into them. Whereas F2 WAT mass was found to be significantly reduced.