All rats fed a high fat and high fructose diets demonstrated a risk factor for metabolic syndrome with fasting blood glucose > 100 mg/dL . After kefir treatments (probiotic and synbiotic kefir) in this study, there were no decrease in blood glucose in rats fed HFHF diet, except for simvastatin treatment. However, a konjac-derived glucomannan supplement (3.6 g/day) administered for 28 days reduced blood lipid and glucose levels by enhancing fecal excretion of neutral sterol and bile acid and alleviated the elevated glucose levels in hyperglycemic diabetic subjects . In contrast to a previous study by , skim milk kefir given at a dose of 3.6 ml/day for 4 weeks could significantly reduce blood glucose levels by 111.00 mg/dL. In the present study, the decrease in low blood glucose was possibly because synbiotic kefir was still not enough to play a role in reducing blood glucose in rats that consumed HFHF diets during the experiment. In the study by , diabetic rats were not fed a HFHF diet. The low dose of glucomannan in kefir and the difference in the conditions of the subjects may not cause a significant reduction in blood glucose levels.
The decrease in blood glucose by simvastatin treatment in this study is in accordance with a previous study by , in which mice fed a high-fat diet and treated with rosuvastatin showed lower blood glucose, which might be due to improved glucose uptake, but beta cell activity is inhibited through lowered insulin levels and inhibited Ca2+ signaling in beta cells, resulting in lowered insulin secretion. Duoble effects on glucose homeostasis by rosuvastatin are due to increased insulin sensitivity, while beta cell activity is inhibited. In another study by , glucose uptake in adipose tissue was upregulated in pravastatin-treated mice fed a high fat/high sucrose diet and db/db mice. In contrast to studies by [20, 21], simvastatins can increase the risk of T2DM, particularly in prediabetic subjects, due to hyperglycemia by impairing the function of islet β cells and have a negative effect on glucose homeostasis, especially on fasting blood glucose levels. Atorvastatin at a high dose causes worsening of glycemic control in patients with DM . According to , individual types of statins may have different effects on glucose metabolism. Based on the results of these studies, the possible effect of statins on blood glucose levels depends on the dose and type of statin and the condition of the subject used for the study.
Porang glucomannan added to kefir could improve glucose metabolism to reduce glycosylated hemoglobin. According to , the synergistic effects of these two components, probiotics and prebiotics, make it a more effective supplement than probiotics or prebiotics separately. In another study by , the fructose diet was rapidly metabolized by the liver, causing changes in carbohydrate and lipid metabolism as well as hepatic inflammation, which led to the development of hyperglycemia, insulin resistance, hyperinsulinemia, and hypertriglyceridemia as major risk factors for diabetes complications. The administration of a high fructose diet (68.35%) over a long period of time can induce complications related to type 2 diabetes, namely, high blood glucose, glycosylated HbA1c, cholesterol, triglycerides and oxidative stress . However, the results indicate that the administration of fermented milk containing the probiotic Lactobacillus rhamnosus GG (150 g/kg standard diet) can reduce the increase in glycosylated hemoglobin (HbA1c) in rats induced by diabetes by feeding high fructose feeds . Additionally, the 24 individuals with T2DM had significantly decreased HbA1c by 7.7% after glucomannan noodle intervention .
Probiotic and synbiotic kefir in the present study could maintain plasma FFA levels in HFHF rats. In a previous study, konjac-glucomannan supplementation (5%) in baboons resulted in lower than baseline values for triglycerides and circulating free fatty acids after 9 weeks . The lower dose of glucomannan from porang tuber in the present study compared to the previous study by  resulted in no decrease in plasma FFA. According to [28, 27], increased levels of circulating FFAs can stimulate fibrinogen synthesis in the liver. Elevated plasma fibrinogen is characteristic of insulin resistance in the liver (insulin may regulate the synthesis of fibribinogen). Glucomannan from konjac, which is fermented in the colon, can decrease FFA production, including propionate, leading to a decrease in fibrinogen synthesis. Therefore, colonie production and absorption of SCFAs (propionate) from soluble fiber may contribute to this fiber's metabolic effects . The various physiological processes, including the control of lipolysis and lipogenesis in adipose tissue, inflammation, endocrine signaling and the composition and characteristics of cellular membranes may be affected by each kind of FFA. The progress of insulin resistance and coagulatory damage may result from the physiological changes caused by changed plasma FFA levels or profiles .
In the present study, porang glucomannan added to kefir can play a role in reducing the occurrence of inflammation through decreased production of pro-inflammatory cytokines in rats fed high-fat high fructose. The effect of soluble fiber in porang glucomannan on the improvement of metabolic disorders is in accordance with a previous study using chitosan fiber , which is given to rats with metabolic disorders (induced by diabetes), can improve insulin resistance and chronic inflammation through decreased lipid absorption and slowed absorption of glucose in the small intestine after eating, resulting in a decrease in hepatic lipids and weight of adipose tissue, and reduced plasma adipocytokine levels including leptin, TNFα and plasminogen activator inhibitor-1 (PAI-1).
In other study, supplementation with a combination of fiber (konjac glucomannan) and bacterial cellulose in high-fat diet-induced obesity in mice had a more positive effect on obesity-associated hepatic inflammation by reducing the levels of TNFα and IL-6 and suppressing the protein expression of nuclear factor erythroid 2–related factor 2 (Nrf-2) in comparison with supplementation with bacterial cellulose or konjac glucomannan alone . In addition, glucomannan and spirulina combination blocks detrimental effects promoted by hypercholesterolemic diets in Zucker rats, one of which could decrease plasma TNFα as one of an inflammation biomarkers .
Normally, PPARγ2 is most abundantly expressed in adipocytes and plays major adipogenic and lipogenic roles in the tissue . Because the rats in the present study received a high-fat and high-fructose diet, it was possible to cause fatty liver. According to [34, 35], in non-alcoholic fatty liver disease (NAFLD) patients and experimental animals there was an increase in the expression of PPARγ in the liver. In addition, in mice fed a high-fat diet showed a high PPARγ expression in the liver .
In the present study, the change in gene expression was the lowest in rat tissue that was treated with synbiotic kefir, although this difference was not significant compared to probiotic kefir treatment. It is possible that kefir-containing probiotics synergize with the prebiotic glucomannan and play a role in the downregulation of PPARγ2 expression in white adipose and hepatic tissue. The result in the present study was similar to that of a previous study , in which mice fed a high-fat diet supplemented with 0.2% kefir powder for 8 weeks lowered PPARγ gene expression in the epididymal fat. In another study, mice fed a high-fat diet and 1 × 107 or 1 × 109 CFU /mice probiotic L. plantarum LG42 supplementation daily for 12 weeks reduced PPARγ expression in adipose tissue . Decreased levels of PPAR-γ and GLUT4 mRNA after high fructose treatment were also enhanced by Lactobacillus reuteri GMNL-263 administration . It was further emphasized by , besides reducing PPARγ expression, the mixed bacterial cellulose and glucomannan from konjac also lowered the protein expression of PPARγ by reducing the size of cells in the adipose tissue of high-fat diet-fed mice.
Consumption of dietary fibers, especially mixed bacterial cellulose/konjac glucomannan, resulted in an improved antioxidant defense system and reduced lipid peroxidation in the liver by increasing the activity of antioxidant enzymes and reducing the formation of malondialdehyde (MDA) in the liver. Moreover, supplementation with these fibers regulated the levels of leptin and adiponectin and inhibited the protein expression of PPARγ by reducing the size of cells in the adipose tissue of high-fat diet-fed mice 
The highest changes in PPAR γ2 gene expression in both adipose and liver tissue of rats treated HFHF without kefir in the present study were in accordance with the results in a previous study , who found that the PPARγ expression level was significantly higher in rats fed a high-fat diet than in rats fed a normal diet, which is mainly related to fat formation. PPARγ2 is also expressed in the liver, specifically in hepatocytes, and its expression level positively correlates with fat accumulation induced by pathological conditions such as obesity and diabetes 
There was no change in the number of Langerhans islets and insulin-producing beta cells in all treatments, indicating that a high-fructose high-fat diet received during the experiment did not cause β-cell damage. This was also evidenced by unchanged average fasting blood glucose levels in HFHF rats before and after being treated with kefir (Table 2). According to , individuals with type 2 diabetes have decreased β-cell mass compared to nondiabetic individuals, and fasting blood glucose will increase if the volume (mass) of cells is less than the 1.1% threshold . If it is below this threshold value, changes in insulin sensitivity and functional damage in insulin secretion will have a major impact on blood glucose. A high fat and high fructose diets in the present study had not yet led to diabetes but only caused prediabetes because blood glucose levels ranged from 100 mg/dL to 125 mg/dL, which is at risk of becoming diabetic (≥ 126 mg/dL), whereas normal blood glucose was < 100 mg/dL [43, 44].
Immunohistochemical staining showed that rats fed HFHF diet without kefir addition had the weakest color intensity. However, rats fed HFHF diet with probiotic or synbiotic kefir showed a strong color intensity as in normal rats (Fig. 1). These result indicate that the probiotic microorganisms in kefir have an important role in improving insulin-producing β-cells. This was supported by a previous studies on diabetic rats treated with konjac extract (containing glucomannan) alone showed less strong in improving insulin-producing β-cells than the rats treated with combination of konjac and inulin extract .