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Journal of Diabetes and Metabolic Disorders logoLink to Journal of Diabetes and Metabolic Disorders
. 2020 Aug 27;19(2):907–914. doi: 10.1007/s40200-020-00578-1

The effects of curcumin and Lactobacillus acidophilus on certain hormones and insulin resistance in rats with metabolic syndrome

Fatma Semina Kapar 1, Gülay Ciftci 1,
PMCID: PMC7843847  PMID: 33553015

Abstract

Purpose

In this study, we tried to investigate the effects of curcumin and Lactobacillus acidophilus probiotics, given individually and in combination, to insulin, adipokines and nitric oxide changes and insulin resistance as experimental treatment of metabolic syndrome.

Methods

Five groups were formed in the study. Fructose (20%) was administered with drinking water for 8 weeks to develop metabolic syndrome. For treatment, curcumin (100 mg/kg/day) and L. acidophilus (2 × 108 cfu/ml/day) were given individually or in combination for the last four weeks. At the end of the experiment; insulin, resistin, leptin, adipokines, apelin and nitric oxide levels were determined by ELISA test kits. Total cholesterol, triglyceride, glucose, albumin and total protein levels were determined by autoanalyzer.

Results

The levels of apelin, resistin, glucose, total cholesterol and triglyceride increased significantly (P < 0.05) in the fructose added to drinking water groups whereas curcumin and L. acidophilus probiotics given individually or together groups for treatment started to decrease and the nitric oxide level decreased significantly. Insulin resistance was found to be significantly higher in the group with metabolic syndrome and insulin resistance developed. In the curcumin and probiotics given group, it was determined that the insulin resistance score was lowered compared to the group only given fructose. The administration of L. acidophilus probiotic and curcumin in rats with metabolic syndrome caused by fructose improves hormone levels and reduces insulin resistance.

Conclusions

These results showed that the addition of dietary curcumin as an antioxidant and probiotic could provide a natural alternative for the treatment of metabolic syndrome induced by fructose.

Keywords: Curcumin, Metabolic syndrome, Lactobacillus acidophilus

Introduction

Metabolic syndrome (MS) is a multidisciplinary condition which includes hyperglycemia, dyslipidemia and abdominal obesity [1]. Two of the most appropriate diagnostic criteria for MS were declared by the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III) and the International Diabetes Federation (IDF) [2, 3]. Fasting plasma glucose, blood pressure (BP), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), and central obesity (waist circumference, WC) are these criteria [4]. A cardinal feature of type 2 diabetes mellitus (T2DM) and metabolic syndrome is insulin resistance, defined as a decreased response to insulin. A number of regulatory hormones derived from adipocytes, called adipokines, have become a focal point of scientific inquiry in recent years. Some of the adipokines hormones such as leptin, adiponectin, resistin, and ghrelin play a role in the regulation of glucose metabolism and are involved in the development of obesity, diabetes, inflammation, auto-immunity and metabolic syndromes [5, 6].

Probiotics are defined as live microorganisms with generally regarded as safe status, which when administered in adequate amounts confer a health benefit on the host [7]. This group's two core members include lactobacilli and bifidobacteria. Ongoing studies show that, oral intake of probiotic lactobacillius; can protect against atopic dermatitis, irritable bowel syndrome, colon cancer, hepatic encephalopathy and can provide recovery for some other diseases [8]. Since probiotics are now well-recognized as effective functional food and dietary ingredients with multiple health-promoting functions along with their ability to combat specific diseases, they are currently the main subject of research worldwide to be explored as potential biotherapeutics in the management of multiple inflammatory metabolic diseases. Probiotic treatment in low or high dose; lowered plasma glucose levels, insulin, triglycerides and oxidative stress levels. Therefore, probiotic administration was thought to be an alternative treatment in metabolic syndrome because it suppressed metabolic syndrome symptoms [9].

Curcumin, diffuloylmethan in other words, is the key natural polyphenol present in the Curcuma Longa (turmeric) rhizomes. Turmeric is a traditional medicinal plant widely used in domestic use for improvinge the taste, color and therapeutic properties without any toxicity in oral administration with phenolic, antidiabetic, antioxidant, anti-inflammatory, antibacterial, antiviral, antifungal and anticancer properties [10].

The research aimed to examine the effects of curcumin and probiotic treatment on insülin, adipokines (resistine, leptin, adiponectin, apelin), nitric oxide, total protein, albumin, glucose, triglyceride and total cholesterol levels and insulin resistance in rats with experimental metabolic syndrome.

Materials and methods

Material

Research place and animal material

Fifty male Sprague-Dawley rats with 10-12 weeks aged, weighed between 300-550 g were used in the study. Rats were obtained from Ondokuz Mayis University Experimental Animals Application and Research Center. Our study has proceeded with the permission of Ondokuz Mayis University Animal Experiments Local Ethics Committee. During the study, 22 ± 2oC room temperature, 60% humidity, 12/12 hours of light/dark environment was provided. Experimental animals were fed ad libitum throughout the study.

Preparation of probiotic suspension

L. acidophilus which used as a treatment, known to be probiotic, was supplied as lyophilized. After diluting the lyophilized bacteria with MRS broth, the bacteria were inoculated to MRS agar for viability and purity control. One ml of the culture, determined to be viable and pure, was added to 500 ml MRS and allowed to incubate at 35°C for 48 h. At the end of the incubation period, the suspension was inoculated to three MRS agar and incubated at 35°C for 48 h. After incubation, bacterial colonies were counted and the amount of bacteria in the main culture was calculated. After the calculation, 1010 cfu/ml bacteria were suspended in the main culture and L. acidophilus probiotic suspension was prepared to be used for treatment [11].

Method

Experiment plan

In this study, 5 groups including 10 rats were formed.

  • Group 1 (n=10) (control group; C): The animals of control group were fed with standard rat food (Table 1) for eight weeks.

  • Group 2 (n=10) (metabolic syndrome group; MS): This group was fed with standard rat food. Its drinking water was mixed with fresh fructose at a rate of 20% and given as ad libitum daily for eight weeks.

  • Group 3 (n=10) (metabolic syndrome group+curcumin; MSC): This group was fed with standard rat food and its drinking water was mixed with fructose rate of 20% given as ad libitum daily for eight weeks. In the last four weeks of the experiment, oral gavage by dissolving curcumin (100 mg/kg/day in 0.5 ml of drinking water) was given for treatment.

  • Group 4 (n=10) (metabolic syndrome+probiotic group; MSL): This group was fed with standard rat food. Its drinking water was mixed with fresh fructose at a rate of 20% and given as ad libitum daily for eight weeks. In the last four weeks of the experiment, L. acidophilus probiotic (2x108 cfu/ml/day) was given for treatment by oral gavage.

  • Group 5 (n=10) (metabolic syndrome+curcumin+probiotic group; MSLC): The animals of this group were fed with standart rat food and its drinking water was mixed with fructose rate of 20% given as ad libitum daily for eight weeks. In the last four weeks of the experiment, curcumin (100 mg/kg/day in 0.5 ml of drinking water) and L. acidophilus probiotic (2x108 cfu/ml/day) was given for treatment via oral gavage.

Table 1.

Serum insulin, leptin, nitric oxide, resistin, adiponectin, apelin levels and HOMA-IR scores

C MS MSC MSL MSLC
Insülin (Mu/mL) 4.39±0.32 a 10.47±0.41 c 6.82±1.23 ab 7.38±1.12 b 6.42±0.5 ab
Leptin (ng/mL) 1.29±0.14 a 2.01±0.11 b 1.57±0.11 a 1.44±0.09 a 1.22±0.11 a
NO (μmol/mL) 17.1±0.69 a 20.22±1.06 b 15.09±0.58 c 18.07±0.65 a 14.63±0.26c
Resistin (ng/mL) 10.79±0.13 a 16.3±0.8 c 12.68±0.17 b 11.83±0.21ab 11.86±0.1ab
Adiponectin (mg/L) 0.48±0.018 a 0.44±0.015 b 0.46±0.009 ab 0.45±0.012 ab 0.45±0.009 ab
Apelin (pg/mL) 629.33±107.11a 922.15±56.74b 537.95±40.62a 531.91±53.9a 558.63±27a
HOMA-IR 1.52±0.17 a 7.31±0.67 d 3±0.46 b 4.61±0.79 c 3.81±0.21 bc

Control group (C), metabolic syndrome group (MS), metabolic syndrome+curcumin group (MSC), metabolic syndrome + probiotic group (MSL) and metabolic syndrome+ probiotic + curcumin (MSLC) group

a, b, c: Differences between groups shown in the same row with different letters are important (P<0.05).

At the end of the eight-week experimental period, the rats were fasted for 12 hours before weighed one by one, allowing only normal drinking water. Rats were anesthetized with 10% ketasol (0.8-1.3ml/kg) and 2% basilazine (2-5 mg/kg) via IP and blood samples were taken from the heart. Blood samples were leaved to stand for 20 minutes in the laboratory for allowed clotting, and then centrifuged for 10 min at 1550 xg. The sera were extracted and diveded into aliquots. Sera were stored at -80 °C until used for the analyses.

Determination of insulin, adipokines, and nitric oxide levels by ELISA

For the determination of insulin, resistin, leptin, adiponectin, apelin and nitric oxide levels in sera of each rat, specific ELISA kits were used. The ELISA’s were performed according to the manufacturer’s instructions, and the absorbances (as OD values) of the ELISA plates were measured by ELISA reader.

The insulin resistance was calculated with the formula of homeostasis model of assesment-insulin resistance (HOMA-IR) as described by Bonora et al. [12].

Determination of some biochemical parameters in sera

Serum triglyceride, total cholesterol, glucose, total protein, and albumin levels were measured by using autoanalyser, spectrophotometrically. In this device; the samples and the reagents were taken by the appropriate dimensions and mixed with standard solutions. The results of the analyses were calculated by optical reading at a certain time and temperature.

Statistical analyses

SPSS statistical software for Windows (SPSS-PC, SPSS Inc., Chicago, Illinois, USA) was used for statistical analysis. One-way analysis of variance (ANOVA), Duncan’s multiple range and Pearson correlation tests were used to determine the differences and relationships among the groups.

Results

Insulin, resistin, leptin, adiponectin, apelin and nitric oxide levels in serum

Insulin levels of C, MS, MSC, MSL and MSLC groups were 4.39±0.32, 10.47±0.41, 6.82±1.23, 7.38±1.12, 6.42±0.5 (Mμ/mL), respectively. It was determined that insulin hormone level increased significantly in MS group (P <0.050) and begun to decrease in MSC, MSL and MSLC groups.

Resistin hormone levels of the C, MS, MSC, MSL and MSLC groups were 10.79±0.13, 16.3±0.8, 12.68±0.17, 11.83±0.21, 11.86±0.1 ng/mL, respectively. Resistin hormone levels were significantly increased in MS group (P <0.050) and begun to decrease in MSC, MSL and MSLC groups.

Leptin levels of the C, MS, MSC, MSL and MSLC groups were 1.29±0.14, 2.01±0.11, 1.57±0.11, 1.44±0.09, 1.22±0.11 ng/mL, respectively. It was determined that serum leptin hormone levels increased significantly in the MS group (P <0.05) and in the MSLC group it was decreased approached the control group.

Adiponectin hormone levels among the C, MS, MSC, MSL and MSLC groups were determined as 0.48±0.018, 0.44±0.015, 0.46±0.009, 0.45±0.012, 0.45±0.009 mg/L, respectively. It was determined that adiponectin hormone level decreased in MS group (P<0. 50) and started to increase in MSC, MSL and MSLC groups.

Apelin hormone levels of the C, MS, MSC, MSL and MSLC groups were 629.33±107.11, 922.15±56.74, 537.95±40.62, 531.91±53.9, 558.63±27 pg/mL, respectively. It was determined that adiponectin hormone levels increased significantly in MS group (P <0.050) and started to decrease in MSC, MSL and MSLC groups.

Nitric oxide levels among the C, MS, MSC, MSL and MSLC groups were 17.1±0.69 20.22±1.06, 15.09±0.58, 18.07±0.65, 14.63±0.26 μmol/mL), respectively. It was determined that nitric oxide levels increased in MS group (P <0.05) and decreased significantly in MSC, MSL and MSLC groups (P <0.05).

The mean HOMA-IR values of the C, MS, MSC, MSL and MSLC groups were determined as 1.52, 7.31, 3, 4.61, 3.81 mg/dL, respectively. Since the HOMA score ≥2.5 is considered as a positive for insulin resistance, the HOMA-IR value was the highest in the MS group and insulin resistance was improved. In the MSC, MSL and MSLC groups, the HOMA-IR score decreased compared to the MS group.

The results of the mean and standard deviation of insulin, resistin, leptin, adiponectin, apelin and nitric oxide levels, and HOMA-IR values are presented in Table 1.

Some biochemical parameter levels in serum

The mean and standard deviation of serum triglyceride, total cholesterol, glucose, total protein, albumin levels of C, MS, MSC, MSL and MSLC groups are presented in the table (mean ± SE) (Table 2).

Table 2.

Serum albumin, total cholesterol, glucose, total protein and triglyceride levels

C MS MSC MSL MSLC
ALB (g/dl) 34.6±0.26 a 36.8±0.41 b 35.5±0.58 a 35.5±0.34 a 36.8±0.32 b
CHO (mg/dl) 34.2±2.39 a 41.4±2.24 b 33.88±2.5 a 33.4±1.94 a 36.5±2.53 ab
GLU (mg/dl) 123.3±2.8 a 280.5±18.58 c 198.55±10.97 b 242.2±24.13 bc 240.6±15.16bc
TP (g/L) 5.99±0.05 a 6.78±0.12 c 6.03±0.11 a 6.18±0.08 ab 6.41±0.42 b
TG (mg/dl) 59.5±5.25 a 218.3±15.54b 160±22.29 b 152.5±12.32 b 136.8±15.06 c

C: Control group, MS: metabolic syndrome group, MSC: metabolic syndrome+curcumin group, MSL: metabolic syndrome+probiotic group, MSLC: metabolic syndrome+ probiotic + curcumin group; ALB: Serum albumin, CHO: total cholesterol, GLU: glucose, TP: total protein TG:triglyceride.

a, b, c:Differences between groups shown in the same row with different letters are important (P<0.05).

Correlation relations

Correlation relations of insulin, leptin, resistin, adiponectin, apelin and nitric oxide levels among the groups are presented in the Tables 3 and 4 (mean ± SE).

Table 3.

Correlation relations of insulin, leptin, resistin, adiponectin, apelin and nitric oxide levels among groups

INS LEP RES ADP APE NO
INS 1 0.560** 0.534** -0.087 0.424** 0.280*
LEP 1 0.558** -0.042 0.624** 0.286*
RES 1 -0.294* 0.444** 0.432**
ADP 1 -0.194 -0.052
APE 1 0.309*
NO 1

INS: insulin, LEP: leptin, RES: resistin, ADP: adiponectin, APE: apelin, NO: nitric oxide

Table 4.

Correlation relations of albumin, cholesterol, glucose, total protein and triglyceride levels among groups

ALB CHO GLU TP TG
ALB 1 0.320* 0.364* 0.787** 0.564**
CHO 1 0.119 0.313* 0.465**
GLU 1 0.402** 0.542**
TP 1 0.633**
TG 1

ALB: albumin, CHO: cholesterol, GLU: glucose, TP: total protein, TG: triglyceride. (P<0.05), **(P<0.01)

When the correlation of insulin, leptin, resistin, adiponectin, apelin and nitric oxide levels was examined among the groups, there was a positive correlation among insulin with leptin, resistin and apelin (r = 0.560**, r = 0.534**, r = 0.624**, respectively). There was a positive correlation (r=0,280*) between insulin level and nitric oxide levels.

There was significant negative correlation between leptin hormone and adiponectin (r=-0.042). There was a significant positive correlation among leptin to resistin and apelin (r=0.558 **, r=0.0624**). Also, there was a significant positive correlation (r=0.286 *) between leptin and nitric oxide levels.

There was a negative correlation (r=-0.294*) between resistin and adiponectin, and a significant negative correlation between apelin and nitric oxide (r=0.444** and r=0.432 **).

A significant positive correlation was found between apelin and nitric oxide (r=0,309*).

There was a positive correlation between insulin and glucose levels (r=0.264) and a significant positive correlation between insulin and HOMA-IR (r=0.863**). There was a significant positive correlation between glucose and HOMA-IR (r=0.649**).

There was a significant positive correlation among albumin level to cholesterol, glucose, total protein and triglyceride levels (r=0.320*, 0.364*, 0.787**, 0.564**).

There was a significant positive correlation among cholesterol, total protein and triglyceride(r=0.313*, 0.465**).

There was a significant positive correlation among glucose, total protein and triglyceride (r=0.402*, 0.542**).

There was a significant positive correlation between total protein and triglyceride (r=0.633**).

Discussion

The use of targeted microbiota agents in the treatment of metabolic diseases, especially diabetes and obesity, has been placed on the agenda with an understanding of the function of intestinal microbiota in the pathophysiology of metabolic illness. Therapeutic probiotics that can manipulate the gut microbiota may also prevent some of the risk factors underlying MS development including dyslipidemia, elevated levels of fasting glucose and insulin resistance. MS is the commonly observed clustering of hyperglycemia, dyslipidemia and abdominal obesity. As a result of the increase in abdominal obesity, sedentary lifestyle and changes in dietary habits, MS is becoming more and more serious problem in the world. High exposure of the liver to fructose has been reported to reduce the sensitivity of insulin by inducing lipogenesis and accumulation of triglycerides [13]. In our study, it was determined that glucose, total cholesterol, triglyceride and insulin levels increased significantly (P <0.05) and metabolic syndrome developed in MS group. Glucose, total cholesterol, triglyceride and insulin levels were decreased in curcumin and L. acidophilus probiotic given groups for treatment. In a study on rats, the effects of curcumin on insulin resistance were investigated. Curcumin has been shown to reduce liver inflammation by increasing insulin sensitivity and decreasing liver necrosis [14]. Panda et al. [15] reported that insulin resistance develops and leads to hyperinsulinemia due to ectopyc lipid deposition in fructose-fed rats. Increased HOMA-IR scores have been reported in rats fed fructose due to high serum insulin levels and high fasting glucose levels. Similarly, in our study, it was determined that insulin hormone levels increased significantly in the group with fructose added to drinking water (P<0.05), then started to decrease in the groups which curcumin and L. acidophilus probiotic given individually or together. Patients with a HOMA score ≥2.5 were considered to be positive for insulin resistance. HOMA-IR was the highest in the MS group and insulin resistance was improved. It was concluded that HOMA-IR scores decreased in the groups that were given probiotic and curcumin compared to MS group.

Curcumin has made significant improvements in all glucose and fat metabolism parameters, oxidative stress, inflammation biomarkers in the presence of metabolic syndrome. Curcumin has been reported to be useful in the treatment of MS due to its ability to modulate oxidation stress and inflammation steps [16]. In a study, the effect of daily intake of curcumin extract for 12 weeks on weight, glucose and lipid profiles in patients with metabolic syndrome was examined. HDL-C was significantly increased and LDL was significantly decreased in patients receiving curcumin. Daily curcumin consumption, especially in patients with metabolic syndrome, has been reported to be an alternative option to change cholesterol-related parameters [17].

In a study, the effects of curcuminoids with increased bioavailability on serum lipid concentrations in MS patients were investigated. Curcuminoid (100 mg/day) or placebo was administered to patients diagnosed with MS for 8 weeks. Curcuminoids were found to be more effective than placebo in lowering serum LDL-C, total cholesterol and triglyceride; in increasing HDL-C concentrations. Curcuminoids are effective adjunctive therapy in patients with MS and it is thought that it may change serum lipid concentrations more than those obtained with standard care [18].

Intestinal microbiota plays an important role in the pathogenesis of metabolic syndrome, as confirmed by studies in both human and animal models. Intestinal microbial composition and functions have been reported to be strongly affected by diet. This intestinal superorganism complex affects the host metabolic balance and hepatic fat storage, which regulates energy absorption, gout motility, appetite, glucose, and lipid metabolism. Probiotic administration can improve bowel barrier integrity, thereby improving metabolic balance and promoting weight loss. However, it has been reported to need more evidence for better understand its clinical effects and therapeutic use [19]. In a study to investigate the effect of probiotics in metabolic syndrome, rats were induced by high fructose diet. Then, probiotics of Lactobacillus curvatus and Lactobacillus plantarum or placebo were given by oral gavage for 3 weeks. Rats fed with high fructose diet showed clinical symptoms of metabolic syndrome such as high plasma glucose, insulin, triglyceride, total cholesterol and oxidative stress levels as well as increased liver mass and liver lipids. Probiotic treatment at high or low dose reduced plasma glucose, insulin, triglycerides and oxidative stress levels; only high-dose probiotic treatment was reported to reduce liver mass and liver lipids [8]. In our study, it was found that glucose levels were significantly increased in the MS group (P <0.05), but in the MSC, MSL and MSLC groups, it was found that the total cholesterol level decreased significantly (P <0.05). It was determined that curcumin and L. acidophilus probiotic decreased glucose level slightly and decreased cholesterol level significantly.

Adipokines, including adiponectin, leptin, resistin and apelin, are peptide hormones secreted primarily by adipose tissue and are associated with metabolic syndrome [20]. Leptin is effective in long-term regulation of energy balance. Leptin suppresses food intake, whereas ghrelin plays a major role in the onset of eating. Obese individuals have hyperleptinemia and low ghrelin levels [21]. Furthermore, obese individuals are resistant to leptin, which was thought to be associated with decreased leptin receptors leading to increased adiposity, dyslipidemia and insulin resistance [22]. Naira et al. [23] found that rats fed with high-fat diet and fructose drinking-water gained weight and were obese; its glucose intolerance, insulin and leptin resistance increased compared to the low-fat diet rats. In our research; serum leptin levels increased significantly in MS group compared to other groups. Serum leptin levels decreased in curcumin and L. acidophilus probiotic given groups and approached to the control group.

Adiponectin mediates insulin function and glucose homeostasis and circulating levels of adiponectin has a negative correlation with body fat mass and insulin resistance [24, 25]. In studies on rhesus monkeys that offer good models of type 2 diabetes, adiponectin levels have been shown to decrease in parallel with insulin resistance and the progression of type 2 diabetes [26]. Increased plasma adiponectin has been reported to be strongly and independently associated with decreased risk of type 2 diabetes in healthy subjects [27]. Adiponectin is present in high concentrations in the circulation of healthy humans and mice. Unlike other adipokines, which levels increase with fat mass, adiponectin levels have been reported to decrease in obesity [28]. Adiponectin levels were much more reduced in individuals with type 2 DM and were reported to have a strong negative correlation with multiple insulin resistance indices [26, 29]. In a study, it was found that individuals with obesity, diabetes mellitus [26] and hypertension [30] have significantly lower adiponectin levels; in addition, plasma adiponectin levels have been reported to may be a marker of the development of type-2-diabetes in the Pima India population [31]. Naira et al. [23] have found that in accordance with previous reports, the serum concentration of adiponectin decreased significantly in rats given high-fat diet and given fructose drinking water. In our research like the other studies, adiponectin hormone levels decreased in MS group. It was determined that adiponectin hormone levels started to increase curcumin, L. acidophilus probiotic given individually or together groups. These observations suggest that plasma adiponectin levels may be closely related to the development of metabolic syndrome.

Weiss et al. [32] examined the prevalence of obesity, metabolic syndrome and its relationship with insulin resistance, C-reactive protein and adiponectin levels in multiethnic with children and adolescents. The prevalence of metabolic syndrome increased with the severity of obesity and reached 50% in severely obese adolescents. The prevalence of metabolic syndrome has been reported to increase significantly as insulin resistance increases (P <0.001 for trend) with the same race and degree of obesity. It has been reported that as obesity increases the C-reactive protein level increases and adiponectin level decreases. The prevalence of metabolic syndrome in obese children and adolescents has been reported to increase as obesity worsens. In a study, the circulating adiponectin levels during the development of metabolic syndrome in a rat model fed with sucrose rich diet was prospectively studied. It was found that the development of metabolic syndrome in rats fed high sucrose diet was not associated with a decrease in circulating adiponectin levels [33].

Xi et al. [34] investigated the effect of crosetine on insulin resistance induced by high fructose diet and its associated abnormalities in male Wistar rats. A number of pathological changes, including insulin resistance, hyperinsulinemia, dyslipidemia and hypertension, have been observed in rats fed fructose. Although fructose feeding did not have a significant effect on body weight, it caused a significant increase in the weight of the epididymal white adipose tissue In addition, there was a significant decrease in both protein and mRNA expression of adiponectin, also there was an increase in tumor necrosis factor (TNF) -α and leptin in epididymal white adipose tissue in rats fed fructose. It has been reported that these disorders were effectively normalized in rats treated with crocetin.

In a study to investigate the effect of swimming on cardiac adiponectin mRNA expression in 40 cholesterol and fructose-fed rats, 40 Sprague-Dawley male rats were divided into two equal groups. The first group was fed a normal diet for 15 weeks while the second group was given high cholesterol and fructose diet (HCFD) for 15 weeks. Ten rats from both groups were swimming during the last 4 weeks and after 15 weeks, serum glucose, insulin, leptin, resistin, adiponectin and cardiac enzymes (lactate dehydrogenase and creatinkinase-MB) levels were measured. In rats fed HCFD, swimming exercises caused an increase in serum adiponectin and a decrease in leptin, resistin and HOMA-IR index. In addition, it was thought that swimming exercise improves ventricular function and this improvement may be related with increased cardiac expression of adiponectin [35].

Apelin is a peptide found in the cardiovascular system, adipose tissue, intestine, pancreas and hypothalamus. Administration of apelin in pharmacological doses stimulates food intake, heart rate and contraction in animals. Administration of peripheral apelin in humans causes nitric oxide-mediated arterial vasodilation. Its presence in adipose tissue leads to inflammation and increased insulin. In a study, it was observed that plasma apelin levels increased in morbid obesity and apelin levels decreased slightly in response to diet-induced weight loss in patients with MS [36]. Apelin is a peptide produced by proximal digestive cells that regulates glucose homeostasis. Dray et al. [37] investigated whether glucose modulates apelin secretion by enterocytes and the effect of apelin on intestinal glucose absorption. As a result, glucose has been shown to increase its secretion from the intestinal lumen to the bloodstream by increasing lumen apelin secretion. Active apelin in the lumen has been reported to regulate carbohydrate flow. Another study in vivo shows that apelin is essential for maintaining systemic insulin sensitivity. Apelin may alter glucose uptake in skeletal myocytes in the absence of endothelial cells. Due to the positive effect of apelin on insulin-glucose homeostasis, it has been reported that apelin/APJ pathway can be utilized for therapeutic benefit in case of insulin resistance [38]. Hyperinsulinemia, insulin resistance and apelin levels have been reported to increase in obese individuals [39]. In our study, it was determined that apelin hormone level increased significantly (P <0.05) in the MS group and it started to decrease in curcumin and probiotic given individually and together groups.

Han et al. [40] investigated the effect of 5% D-allulose supplementation on body fat mass in high-fat diet-induced obesity (HFD). Mice were given a HFD with or without sugar substitutes (D-glutoseose, D-fructose, erythrite or D-allulose) for 16 weeks. It was observed that body weight, fat mass, plasma leptin and resistin concentrations in D-allulose group decreased well compared to the control group. In our study, it was found that resistin hormone levels increased significantly in the MS group (P <0.050) and it started to decrease in curcumin and probiotic individually and together given groups.

High fructose or high fat diet leads to the development of oxidative stress. In addition, the severity of oxidative stress is higher when a fructose-rich diet is consumed compared to a fat-rich diet. Curcumin intake is known to improve redox balance by improving antioxidant defense systems [41]. NO is thought to be directly or indirectly related to food consumption. During diet treatment of obesity, NO production increases in the hypothalamic saturation center. It was thought that NO might be a central regulator in food consumption associated with neuropeptides [42]. In our study, it was determined that nitric oxide levels were increased in the MS group (P <0.05) and it decreased significantly in curcumin and probiotic given individually and together groups (P <0.05).

In conclusion, it was concluded that the use of curcumin antioxidant in combination with L. acidophilus probiotic for the treatment of metabolic syndrome is beneficial in reducing metabolic syndrome markers.

Acknowledgements

This research was supported by the Scientific Research Projects Commission of Ondokuz Mayis University (Contract Grand Number: PYO-VET.1904.16.020).

Compliance with ethical standards

Conflict of interest

The authors have declared that no competing interests exist.

Footnotes

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References

  • 1.Solak A, Tuncal P. Leptin, adiponectin, oxidized LDL levels and paraoxonase activity in Metabolic Syndrome. Turk J Clin Biochem. 2009;7(1):22–9. [Google Scholar]
  • 2.Deepa M, Farooq S, Datt M, Deepa R, Mohan V. Prevalence of metabolic syndrome using WHO, ATPIII and IDF definitions in Asian Indians: The Chennai Urban Rural Epidemiology Study (CURES-34) Diabetes Metab Res Rev. 2007;23(2):127–34. doi: 10.1002/dmrr.658. [DOI] [PubMed] [Google Scholar]
  • 3.Kelliny C, William J, Riesen W, Paccaud F, Bovet P. Metabolic syndrome according to different definitions in a rapidly developing country of the African region. Cardiovasc Diabetol. 2008;7:27. doi: 10.1186/1475-2840-7-27. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Rezaianzadeh A, Namayandeh SM, Sadr SM. National cholesterol education program adult treatment panel III versus international diabetic federation definition of metabolic syndrome, which one is associated with diabetes mellitus and coronary artery disease? Int J Prev Med. 2012;3(8):552–8. [PMC free article] [PubMed] [Google Scholar]
  • 5.Tilg H, Moschen AR. Role of adiponectin and PBEF/visfatin as regulators of inflammation: involvement in obesity-associated diseases. Clin Sci. 2008;114:275–88. doi: 10.1042/CS20070196. [DOI] [PubMed] [Google Scholar]
  • 6.Huang H, Korivi M, Tsai CH, Yang JH, Tsai YC. Supplementation of Lactobacillus plantarum K68 and fruit-vegetable ferment along with high fat-fructose diet attenuates Metabolic Syndrome in rats with insulin resistance. Evid Based Complement Alternat Med. 2013;94:3020. doi: 10.1155/2013/943020. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.FAO/WHO. Working Group Report on Drafting Guidelines for the Evaluation of Probiotics in Food London, Ontario, Canada: 2002.
  • 8.Özden A. Gastro-intestinal Sistem ve Probiyotik-Prebiyotik Sinbiyotik, Ankara Üniversitesi Tıp Fakültesi, Gastroenteroloji Bilim Dalı. Eylül: Ankara, Güncel Gastroenteroloji; 2005. [Google Scholar]
  • 9.Park DY, Ahn YT, Huh CS, McGregor RA, Choi MS. Dual probiotic strains suppress high fructose-induced metabolic syndrome. World J Gastroenterol. 2013;19:274–83. doi: 10.3748/wjg.v19.i2.274. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Nelson KM, Dahlin JL, Bisson J, Graham J, Pauli GF, Walters MA. The essential medicinal chemistry of curcumin. J Med Chem. 2017;60(5):1620–37. doi: 10.1021/acs.jmedchem.6b00975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Park YH, Kim JG, Shin YW, Kim SH, Whang KY. Effect of dietary inclusion of Lactobacillus acidophilus ATCC 43121 on cholesterol metabolism in rats. J Microbiol Biotechnol. 2006;17(4):655–62. [PubMed] [Google Scholar]
  • 12.Bonora E, Targher G, Alberiche M, Bonadonna RC, Saggiani F, Zenere MB. Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glu cose tolerance and insulin sensitivity. Diabet Care. 2000;23:57–63. doi: 10.2337/diacare.23.1.57. [DOI] [PubMed] [Google Scholar]
  • 13.Dornas WC, Lima WG, Pedrosa ML, Silva ME. Health implications of high-fructose intake and current research. Adv Nutr. 2015;6:729–37. doi: 10.3945/an.114.008144. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Mohammadi S, Bardei LK, Hojati V, Ghorbani AG, Nabiuni M. Anti-inflammatory effects of curcumin on insulin resistance index, levels of interleukin-6, C-reactive protein, and liver histology in polycystic ovary syndrome-induced rats. Cell J. 2017;19(3):425–33. doi: 10.22074/cellj.2017.4415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Panda V, Mistry K, Sudhamani S, Nandave M, Ojha SK. Amelioration of abnormalities associated with the Metabolic Syndrome by Spinacia oleracea consumption and aerobic exercise in rats. Oxid Med Cell Longev. 2017;1:1–15. doi: 10.1155/2017/2359389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Kelany ME, Hakami TM, Omar AH. Curcumin improves the metabolic syndrome in high-fructose-diet-fed rats: role of TNF-α, NF-κB, and oxidative stress. Can J Physiol Pharmacol. 2017;95(2):140–50. doi: 10.1139/cjpp-2016-0152. [DOI] [PubMed] [Google Scholar]
  • 17.Yang YS, Su YF, Yang HW, Lee YH, Chou I, Ueng JI. KC. Lipid-lowering effects of curcumin in patients with Metabolic Syndrome: A randomized, double-blind, placebo-controlled trial. Phytother Res. 2014;28:1770–7. [DOI] [PubMed]
  • 18.Panahia Y, Khalilib N, Sadat Hosseinib M, Abbasinazaric M, Sahebkard A. Lipid-modifying effects of adjunctive therapy with curcuminoids piperine combination in patients with metabolic syndrome: results of a randomized controlled trial. Complement Ther Med. 2014;22:851–7. [DOI] [PubMed]
  • 19.Festi D, Schiumerini R, Eusebi HL, Marasco G, Taddia M, Colecchia A. Gut microbiota and metabolic syndrome. World J Gastroenterol. 2014;20(43):16079–94. doi: 10.3748/wjg.v20.i43.16079. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Raucci R, Rusolo F, Sharma A, Colonna G, Castello G, Costantini S. Functional and structural features of adipokine family. Cytokine. 2013;61:1–14. doi: 10.1016/j.cyto.2012.08.036. [DOI] [PubMed] [Google Scholar]
  • 21.Klok MD, Jakobsdottir S, Drent ML. The role of leptin and ghrelin in theregulation of food intake and body weight in humans: a review. Obes Rev. 2007;8:21–34. doi: 10.1111/j.1467-789X.2006.00270.x. [DOI] [PubMed] [Google Scholar]
  • 22.Myers MG, Cowley MA, Münzberg H. Mechanisms of leptin action and leptin resistance. Annu Rev Physiol. 2008;70:537–56. doi: 10.1146/annurev.physiol.70.113006.100707. [DOI] [PubMed] [Google Scholar]
  • 23.Naira S, Gagnona J, Pelletiera C, et al. Shrimp oil extracted from the shrimp processing waste reduces the development of insulin resistance and metabolic phenotypes in diet-induced obese rats. Appl Physiol Nutr Metab. 2017;42(8):841–9. doi: 10.1139/apnm-2016-0644. [DOI] [PubMed] [Google Scholar]
  • 24.Yamauchi T, Kamon J, Waki H, et al. The fat derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med. 2001;7(8):941–6. doi: 10.1038/90984. [DOI] [PubMed] [Google Scholar]
  • 25.Jung UJ, Choi MS. Obesity and its metabolic complications: the role ofadipokines and the relationship between obesity, inflammation, insulin resistance, dyslipidemia and nonalcoholic fatty liver disease. Int J Mol Sci. 2014;15(4):6184–223. doi: 10.3390/ijms15046184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Hotta K, Funahashi T, Arita Y, et al. Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol. 2000;20:1595–9. doi: 10.1161/01.ATV.20.6.1595. [DOI] [PubMed] [Google Scholar]
  • 27.Spranger J, Kroke A, Möhlig M, Bergmann MM, Ristow M, Boeing H, Pfeiffer AF. Adiponectin and protection against type 2 diabetes mellitus. Lancet. 2003;361:226–8. doi: 10.1016/S0140-6736(03)12255-6. [DOI] [PubMed] [Google Scholar]
  • 28.Arita Y, Kihara S, Ouchi N. Paradoxical decrease of an adipose specific protein, adiponectin, in obesity. Biochem Biophys Res Commun. 1999;257:79–83. doi: 10.1006/bbrc.1999.0255. [DOI] [PubMed] [Google Scholar]
  • 29.Weyer C, Funahashi T, Tanaka S, et al. Hypoadiponectinemia in Obesity and Type 2 Diabetes: Close Association with Insulin Resistance and Hyperinsulinemia. J Clin Endocrinol Metab. 2001;86:1930–5. doi: 10.1210/jcem.86.5.7463. [DOI] [PubMed] [Google Scholar]
  • 30.Adamczak M, Wiecek A, Funahashi T, Chudek J, Matsuzawa Y. Decreased plasma adiponectin concentration in patients with essential hypertension. Am J Hypertens. 2003;16:72–5. doi: 10.1016/S0895-7061(02)03197-7. [DOI] [PubMed] [Google Scholar]
  • 31.Lindsay RS, Funahashi T, Hanson RL, Matsuzawa Y, Tanaka S, Tataranni PA, Knowler WC, Krakoff J. Adiponectin and development of type 2 diabetes in the Pima Indian population. Lancet. 2002;360:57–8. doi: 10.1016/S0140-6736(02)09335-2. [DOI] [PubMed] [Google Scholar]
  • 32.Weiss R, Dziura J, Burgert TS, Tamborlane WV, Taksali SE, Yeckel CW, Allen K, Lopes M, Savoye M, Morrison J, Sherwin RS, Caprio S. Obesity and the Metabolic Syndrome in children and adolescents. J Med. 2004;350:23. doi: 10.1056/NEJMoa031049. [DOI] [PubMed] [Google Scholar]
  • 33.Aslam M, Madhu SV. Development of metabolic syndrome in high-sucrose diet fed rats is not associated with decrease in adiponectin levels. Endocrine. 2017;58:59–65. doi: 10.1007/s12020-017-1403-5. [DOI] [PubMed] [Google Scholar]
  • 34.Xi L, Qian Z, Xu G, Zheng S, Sun S, Wen N, Sheng L, Shi Y, Zhang Y. Beneficial impact of crocetin, a carotenoid from saffron, on insulin sensitivity in fructose-fed rats. J Nutr Biochem. 2007;18:64–72. doi: 10.1016/j.jnutbio.2006.03.010. [DOI] [PubMed] [Google Scholar]
  • 35.Sakr HF. Modulation of metabolic and cardiac dysfunctions by swimming in overweight rats on a high cholesterol and fructose diet: possible role of adiponectin. J Physiol Pharmacol. 2013;64(2):231–40. [PubMed] [Google Scholar]
  • 36.Heinonen MV, Laaksonen DE, Karhu T, Karhunen L, Laitinen T, Kainulainen S. Effects of diet-induced weight loss on plasma apelinand cytokine levels in individuals with metabolic syndrome. Nutr Metab Cardiovasc Dis. 2009;19:626–33. doi: 10.1016/j.numecd.2008.12.008. [DOI] [PubMed] [Google Scholar]
  • 37.Dray C, Sakar Y, Vinel C, Daviaud D, Masri B, Garrigues L. The intestinal glucose-apelin cycle controls carbohydate absorption in mice. Gastroenterol. 2013;144:771–80. doi: 10.1053/j.gastro.2013.01.004. [DOI] [PubMed] [Google Scholar]
  • 38.Yue P, Jin H, Marissa A, Deng AC, Azuma J, Asagami T, Kundu RK, Reaven GM, Quertermous T, Tsao PS. Apelin is necessary for the maintenance of insulin sensitivity. Am J Physiol Endocrinol Metab. 2010;298:59–67. doi: 10.1152/ajpendo.00385.2009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39.Beltowski J. Apelin and visfatin: Unique “beneficial” adipokines upregulated in obesity? Med Sci Monit. 2006;12:112–9. [PubMed] [Google Scholar]
  • 40.Han Y, Han HJ, Kim AH, Choi JY, Cho SJ, Park YB, Un JJ, Choi MS. D-Allulose supplementation normalized the body weight nd fat-pad mass in diet-induced obese mice via the regulation of lipid metabolism under isocaloric fed condition. Mol Nutr Food Res. 2016;60:1695–706. doi: 10.1002/mnfr.201500771. [DOI] [PubMed] [Google Scholar]
  • 41.Selvi NMK, Sridhar MG, Swaminathan RP, Sripradha R, Badhe B. Curcumin inhibits hyperlipidemia and hepatic fat accumulation in high-fructose-fed male Wistar rats. Pharm Biol. 2016;54(12):2857–63. doi: 10.1080/13880209.2016.1187179. [DOI] [PubMed] [Google Scholar]
  • 42.Jang EH, Park CS, Lee SK, Pie JE, Kang JH. Excessive nitric oxide attenuates leptin-mediated signal transducer and activator of transcription 3 activation. Life Sci. 2007;80(7):609–17. doi: 10.1016/j.lfs.2006.10.007. [DOI] [PubMed] [Google Scholar]

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