This study is the first to demonstrate that dual fermentation of rice bran enriches the functional ingredients in rice bran. FRB therefore contains higher levels of lipid, dietary fibre, and phenolic compounds more than Non-FRB does (Table 2). The results obtained from this study indicate that FRB improves hypertension, insulin resistance, glucose impairment, serum adiponectin level, and AMPK activation in SHRSP. Thus, FRB may be a potent functional food that can be used for the management of metabolic syndrome.
Adiponectin is an important adipokine for insulin sensitization and is involved in some homeostatic functions such as the regulation of glucose and lipid metabolism [26]. A recent study showed that antihypertensive drugs could improve the sensitivities of adiponectin and leptin in SHRSP [27]. In the present study, FRB improved adiponectin and leptin impairments in SHRSP, which results in an improvement in glucose and lipid metabolism. Plasma adiponectin levels are inversely related to adiposity and directly associated with leptin sensitivity [28]. Thus, it appears that FRB exerted its action on leptin sensitivity and body fat mass via the stimulation of adiponectin secretion even though the exact mechanisms involved are still unknown.
Phenolic compounds and dietary fibre are used in formulating food products to improve the functionalities and health benefits of such products. Phenolic compounds and dietary fibre produce health benefits by reducing cholesterolemia, modifying glycemic responses, and preventing the development of cardiovascular diseases [29, 30]. Microorganisms are used in the brewing and food industries to produce fermented products. They are also used to produce aroma compounds and secondary metabolites for use in processed foods. Our results confirm that FRB is a functional food that can be effective in the management of metabolic syndrome and for the prevention of lifestyle-related diseases.
We observed that after administration, a single oral dose of FRB (2 g/kg body weight) lowers BP within 6 h. We also found that FRB has the capacity to decrease plasma glucose and insulin levels (Fig. 1). Chronic supplementation with 5 % FRB for 4 weeks increased serum ACE inhibitory activity (Fig. 2). This corroborates the results in a previous report, which indicated that fractions of enzyme-treated rice bran improved BP elevation in SHRSP via the inhibition of ACE activity [21]. Furthermore, FRB supplementation enhanced serum adiponectin levels (both high molecular weight and total adiponectin) and improved serum and liver lipid profiles (Table 3). FRB supplementation also improved glucose tolerance and insulin resistance (Fig. 3). It was shown in a previous study that L-tryptophan, which is one of the identified functional ingredients in enzyme-treated rice bran, improved blood pressure as well as blood glucose and insulin levels [31]. It was observed that the L-tryptophan content of FRB (30 mg/100 g) is much higher than that of Non-FRB (4 mg/100 g). In the liver, there is de novo glucose synthesis mainly from lactate, alanine, pyruvate, and glycerol. In the present study, FRB reduced the mRNA levels of enzymes involved in gluconeogenesis (PEPCK and G6PC), which are the rate limiting enzymes in gluconeogenesis. Insulin can inhibit the transcriptional activity of forkhead box protein O1, which regulates the transcription of PEPCK. The aforementioned mechanisms were therefore involved in the improvements in serum glucose and insulin levels by FRB in this study. Studies have shown that brown rice bran and enzyme-treated rice bran improve glucose tolerance and insulin resistance in mouse and rat models [21, 32]. Altogether, our results suggest that FRB regulates glucose and lipid metabolism and contributes effectively to improving hypertension in SHRSP better than Non-FRB does.
Moreover, we observed that LXR?, SREBP-1c, and ChREBP? mRNA expression levels were downregulated after FRB supplementation in the SHRSP. Glucose and insulin coordinate hepatic lipogenesis and the glycolytic gene expression [33]. Both glucose and insulin are potent factors that are involved in inducing the transcription of key enzyme genes in glycolysis and de novo lipogenesis [34]. It has been found that rice bran derivatives reduce plasma and liver lipids, whereas protein hydrolysates from rice bran improve insulin and leptin sensitivity in high-fat diet-induced metabolic syndrome in hamsters [6, 14]. Insulin triggers the transcriptions of glycolytic and lipogenic enzymes by activating SREBP-1c and LXR? [35, 36]. Therefore, chronic supplementation with FRB downregulated the mRNA expression levels of LXR?, SREBP-1c, and ChREBP?, as well as their target genes such as G6PC, PEPCK, HMGCR, FASN, SCD1, and ACC in the liver (Fig. 4). Thus, the decreased serum glucose and liver TG levels due to the intake of FRB may have been caused by an enhanced serum level of adiponectin, which regulates glucose and lipid metabolism.
FRB increased the activation of AMPK in the liver (Fig. 5) and quantitative western blot analysis showed that FRB increased the phosphorylation of AMPK?. This indicates that FRB may activate the adiponectin/AMPK signalling pathway. A study in humans has shown that plasma adiponectin concentration negatively correlates with lipid metabolism [37]. However, a previous study demonstrated that the phosphorylation and activation of AMPK are stimulated by adiponectin in the liver. The study also indicated that adiponectin improved insulin sensitivity and decreased plasma glucose levels via the AMPK-peroxisome proliferator-activated receptor gamma coactivator 1-alpha signalling pathway in the liver [38].
The results of the current study verified that the intake of FRB could increase plasma adiponectin levels. This results in an activation of AMPK and a downregulation of the mRNA expression of genes involved in gluconeogenesis and lipogenesis in the liver. This suggests that enhancing serum adiponectin levels and downregulating transcription factors involved in hepatic glucose and fat metabolism may be a promising strategy to prevent metabolic-related diseases characterized by insulin resistance and hyperlipidemia. Therefore, dietary supplementation with FRB can mitigate metabolic syndrome.