White button mushroom (Agaricus bisporus) lowers blood glucose and cholesterol levels in diabetic and hypercholesterolemic rats

Agaricus bisporus (white button mushroom; WBM) contains high levels of dietary fibers and antioxidants including vitamin C, D, and B₁₂; folates; and polyphenols that may provide beneficial effects on cardiovascular and diabetic diseases. The objective of this study was to examine the hypothesis that intake of the fruiting bodies of WBM regulates anticholesterolemic and antiglycemic responses in rats fed a hypercholesterolemic diet (0.5% cholesterol; 14% fat) and rats with type 2 diabetes induced by injection of streptozotocin (STZ) (50 mg/kg body weight), respectively. The STZ-induced diabetic male Sprague-Dawley rats fed the Agaricus bisporus powder (ABP; 200 mg/kg of body weight) for 3 weeks had significantly reduced plasma glucose and triglyceride (TG) concentrations (24.7% and 39.1%, respectively), liver enzyme activities, alanine aminotransferase and aspartate aminotransferase (11.7% and 15.7%, respectively), and liver weight gain (P < .05). In hypercholesterolemic rats, oral feeding of ABP for 4 weeks resulted in a significant decrease in plasma total cholesterol (TC) and low-density lipoprotein (LDL) (22.8% and 33.1%, respectively) (P < .05). A similar significant decrease in hepatic cholesterol and TG concentrations was observed (36.2% and 20.8%, respectively) (P < .05). Decrease in TC, LDL, and TG concentrations was accompanied by a significant increase in plasma high-density lipoprotein concentrations. It was concluded that A bisporus mushroom had both hypoglycemic and hypolipidemic activity in rats.     

Dietary polyunsaturated fatty acids slow the progression of diabetic nephropathy in streptozotocin-induced diabetic rats

Diabetic nephropathy is associated with lipid deposits in the kidney. We hypothesized that a diet containing polyunsaturated fatty acids (PUFAs) could ameliorate pathogenesis of diabetic kidney diseases associated with lipid depositions in the kidneys. We examined if the pathogenesis and progression of diabetic nephropathy are affected by the type of dietary fat using streptozotocin (45 mg/kg body weight, intravenous)-induced diabetic rats (5-week-old male Sprague-Dawley rats). Streptozotocin-induced diabetic rats were fed a lard diet containing saturated fatty acids or a rapeseed oil diet containing PUFAs (DML and DMR, respectively) for 11 days. Similarly, streptozotocin-nontreated rats were fed a lard diet or a rapeseed oil diet (NL and NR, respectively) for 11 days. Hyperglycemia was induced in DML and DMR, compared with NL and NR groups. The levels of plasma ketone, total cholesterol, and triglyceride (TG) were significantly increased in the DML group. Moreover, albuminuria and renal TG content were enhanced in the DML group. The renal TG content correlated positively with urinary albumin excretion (P < .001). Oil-Red O staining of kidney sections indicated a marked accumulation of neutral lipids in both glomerular and tubular cells in the DML group. In addition, a renal sterol regulatory element-binding protein-1 mature protein increment was induced in the DML group. Conversely, sterol regulatory element-binding protein-1 expression in the kidney was maintained at normal levels in the DMR group. These results suggest that dietary PUFAs may slow the progression of diabetic nephropathy associated with lipid depositions in the kidney.     

Combined extractives of red yeast rice,bitter gourd,chlorella, soy protein,and licorice improve total cholesterol,low-density lipoprotein cholesterol,and triglyceride in subjects with metabolic syndrome

In this study, we aimed to examine the effects of a plant-extractive compound on lipid profiles in subjects with metabolic syndrome. We hypothesized that extractives from red yeast rice, bitter gourd, chlorella, soy protein, and licorice have synergistic benefits on cholesterol and metabolic syndrome. In this double-blinded study, adult subjects with metabolic syndrome were randomized to receive a plant-extractive compound or a placebo treatment for 12 weeks. Both total cholesterol (5.4 ± 0.8 to 4.4 ± 0.6 mmol/L, P < .001) and low-density lipoprotein cholesterol (3.4 ± 0.7 to 2.7 ± 0.5 mmol/L, P < .001) were significantly reduced after treatment with the plant extractives, and the magnitudes of reduction were significantly greater than in the placebo group (−1.0 ± 0.6 vs 0.0 ± 0.6mmol/L, P < .001; −0.7 ± 0.6 vs 0.0 ± 0.6 mmol/L, P < .001). The reduction in the fasting triglycerides level was significantly greater in the plant-extractive group than in the placebo group (−0.5 ± 0.8 vs −0.2 ± 1.0 mmol/L, P = .039). There was also a significantly greater reduction in the proportion of subjects with hypertensive criteria in the plant-extractive group than in the placebo group (P = .040). In conclusion, the plant extractives from red yeast rice, bitter gourd, chlorella, soy protein, and licorice were effective in reducing total and low-density lipoprotein cholesterol. The plant extractives also showed potential for reducing triglyceride and normalizing blood pressure.     

Opuntia humifusa stems lower blood glucose and cholesterol levels in streptozotocin-induced diabetic rats

The Opuntia humifusa stem (OHSt) contains high levels of antioxidants including vitamin C, flavonoids, and polyphenols that may prove beneficial in treating diabetes mellitus. The objective of this study was to examine the hypothesis that intake of the OHSt regulates blood glucose levels and hypolipidemic responses in rats with diabetes mellitus induced by injection of streptozotocin. Forty Sprague-Dawley rats (6 weeks of age) were assigned to 5 groups: normal control, rats with streptozotocin-induced diabetes mellitus (DM), DM treated with OHSt 150 mg/kg per day, DM treated with OHSt 250 mg/kg per day, and DM treated with OHSt 500 mg/kg per day. Powdered OHSt was suspended in distilled water and administered orally through the sonde once daily. After 7 weeks of treatment, the fasting blood glucose and triglyceride levels of the OHSt groups were significantly lower when compared with the DM group (P < .05). Treatment with the OHSt also resulted in a significant decrease in serum total cholesterol and low-density lipoprotein cholesterol (P < .05). Decreases in both total cholesterol and low-density lipoprotein cholesterol were accompanied by a significant increase in serum high-density lipoprotein cholesterol (P < .05). Furthermore, levels of alanine aminotransferase and aspartate aminotransferase were significantly lower in the OHSt groups than in the DM group (P < .05). In addition, a significant increase in relative beta cell volume of pancreas was observed in rats treated with 500 mg/kg of OHSt when compared with the untreated DM rats (P < .05). The overall results suggest that the OHSt possesses potential hypoglycemic and hypolipidemic activity in streptozotocin-induced diabetic rats.     

Dietary intervention with green dwarf banana flour (Musa sp AAA) prevents intestinal inflammation in a trinitrobenzenesulfonic acid model of rat colitis

Dietary products are among the therapeutic approaches used to modify intestinal microflora and to promote protective effects during the intestinal inflammatory process. Because the banana plant is rich in resistant starch, which is used by colonic microbiota for the anaerobic production of the short-chain fatty acids that serve as a major fuel source for colonocytes: first, green dwarf banana flour produces protective effects on the intestinal inflammation acting as a prebiotic and, second, combination of this dietary supplementation with prednisolone presents synergistic effects. For this, we used the trinitrobenzenesulphonic acid (TNBS) model of rat colitis. Our results revealed that the protective effect produced by a combination of 10% green dwarf banana flour with prednisolone was more pronounced than those promoted by a single administration of prednisolone or a diet containing 10% or 20% banana flour. This beneficial effect was associated with an improvement in the colonic oxidative status because the banana flour diet prevented the glutathione depletion and inhibited myeloperoxidase activity and lipid peroxidation. In addition, the intestinal anti-inflammatory activity was associated with an inhibition of alkaline phosphatase activity, a reduction in macroscopic and microscopic scores, and an extension of the lesions. In conclusion, the dietary use of the green dwarf banana flour constitutes an important dietary supplement and complementary medicine product to prevention and treatment of human inflammatory bowel disease.     

Iridoid extracts from Ajuga iva increase the antioxidant enzyme activities in red blood cells of rats fed a cholesterol-rich diet

The lyophilized aqueous extract of Ajuga iva (Ai) is able to reduce oxidative stress, which may prevent lipid peroxidation in hypercholesterolemic rats. Iridoids (I) were isolated from Ai. We hypothesized that the antioxidant defense status in red blood cells (RBC) and tissues in rats fed a cholesterol-rich diet and treated with Ai may be correlated to these compounds. Male Wistar rats (n = 32) weighing 120 ± 5 g were fed a diet containing 1% cholesterol for 15 days. After this phase, hypercholesterolemic (HC) rats were divided into groups, fed the same diet, and received either the same or different doses (5, 10, or 15 mg/kg body weight by intraperitoneal injection) of I for 15 days. Compared with the HC group, total cholesterol value was 1.4- and 1.2-fold lower in the I₅-HC and I₁₀-HC groups. Serum thiobarbituric acid reactive substance content was 2.3-, 2.9-, and 3-fold lower in the I₅-HC, I₁₀-HC, and I₁₅-HC groups compared with the HC group. In RBC, glutathione peroxidase, glutathione reductase, and superoxide dismutase activities were significantly higher in the I₅-HC, I₁₀-HC, and I₁₅-HC groups than the HC group. Liver, heart, and muscle glutathione peroxidase and superoxide dismutase activities were significantly higher in the groups treated with I than the HC group. Muscle glutathione reductase activity was increased 1.4-fold in the I₅-HC, 1.5-fold in the I₁₀-HC, and 1.5-fold in the I₁₅-HC group. In HC rats, different doses of I increase the antioxidant enzyme activities in RBC and act differently in tissues. Treatment with I may play an important role in suppressing oxidative stress caused by dietary cholesterol and, thus, may be useful for the prevention and/or early treatment of hypercholesterolemia.     

Dietary fat level affects tissue iron levels but not the iron regulatory gene HAMP in rats

Because dietary fats affect the regulation and use of body iron, we hypothesized that iron regulatory and transport genes may be affected by dietary fat. A model of early-stage I to II, nonalcoholic fatty liver was used in which rats were fed standard (35% energy from fat) or high-fat (71% energy from fat) liquid diets with normal iron content (STD/HF groups). In addition, intraperitoneal injections of iron dextran were given to iron-loaded (STD+/HF+ groups) and iron-deficient diets to STD−/HF− groups. Plasma osmolality, hemoglobin level, and mean corpuscular hemoglobin concentration were increased in all STD diet groups compared with all HF diet groups. Plasma iron and transferrin saturation were affected by an interaction between dietary fat and iron. They were high in the STD group (normal iron) compared with their respective HF group. Similarly, this group also showed a 4-fold increase in the messenger RNA expression of the hepatic hemochromatosis gene. Spleen iron was high in the iron-loaded STD+ group compared with all other groups. Hepatic iron and messenger RNA expression of peroxisome proliferator–activated receptor-γ, CCAAT/enhancer binding protein α, interleukin-6, and iron transport genes (transferrin receptor 2, divalent metal transporter 1 iron-responsive element, and divalent metal transporter 1 non–iron-responsive element) were increased, whereas tumor necrosis factor α was decreased in the HF diet groups. The expression of iron regulatory gene HAMP was not increased in the HF diet groups. Iron regulatory and transport genes involved in cellular and systemic iron homeostasis may be affected by the macronutrient composition of the diet.     

A mixture of Salacia reticulata (Kotala himbutu) aqueous extract and cyclodextrin reduces body weight gain,visceral fat accumulation,and total cholesterol and insulin increases in male Wistar fatty rats

This study examined the effects of a mixture of an aqueous extract of Salacia reticulata (Kotala himbutu) and cyclodextrin (SRCD) on various metabolic parameters and cecal fermentation in obese fa/fa male Wistar fatty rats, a model of type 2 diabetes mellitus. Wistar fatty rats were fed 0% (control group) or 0.2% SRCD-supplemented diets and weighed weekly. The plasma glucose, triacylglycerol, total cholesterol, insulin, and adiponectin concentrations were measured at weeks 0, 2, 4, and 5. SRCD supplementation suppressed the time-dependent increase in the plasma total cholesterol and insulin concentrations. After 6 weeks of a 0.2% SRCD-supplemented diet, the body weight gain, food intake, visceral fat mass, liver mass, and liver triacylglycerol content of the rats were significantly lower, whereas the plasma adiponectin concentrations were significantly higher than those of the control group. SRCD supplementation had no significant effect on plasma glucose and triacylglycerol concentrations. SRCD supplementation significantly increased cecum mass, whereas it significantly decreased the cecal butyrate and short-chain fatty acid (sum of the acetate, butyrate, and propionate) concentrations. All of the rats were subjected to an oral glucose tolerance test at the beginning of week 6. The area under the curve for insulin was significantly smaller with SRCD supplementation and showed no change in glucose tolerance compared to that of the control group. These results suggest that bioactive compounds in SRCD may suppress the development of type 2 diabetes mellitus by influencing glucose and lipid metabolism in male Wistar fatty rats and that SRCD may influence cecal fermentation.     

Feed withdrawal abate regimens lipodystrophy and metabolic syndrome symptoms,such as glucose tolerance,are associated with the diameter of retroperitoneal adipocytes in rats

Adipocyte numbers were increased by feed withdrawal (FW) regimens in cattle; thus, the effect of FW regimens was studied in male Wistar and fa/fa obese rats, as models for humans, in 2 completely randomized design experiments to abate lipodystrophy and progression of metabolic syndrome symptoms. The hypothesis was that application of FW regimens could alter adipose tissue cellularity, adipocyte size, and affect area under the curve (AUC) during glucose tolerance tests. Objectives were to determine associations among retroperitoneal and inguinal adipose tissue adipocyte number, diameter, and AUC, as affected by fortnightly or a single (at age 50 days) 24-hour FW regimen. Adipocyte marker peroxisome proliferator–activated receptor γ expression was elevated (P = .054) in the retroperitoneal tissue of fa/fa obese rats in the fortnightly FW treatment because of a 13% increase in tissue cell density (cells per gram; P = .13). Average cell diameter in retroperitoneal adipose and AUC were negatively corelated. Regression analyses after including the square of average cell diameter indicated that average retroperitoneal adipocyte diameter (between 65 and 135 μm) and the AUC were related in a quadratic manner (R² = 0.14; n = 49; P = .03) for Wistar rats. Cell number of the inguinal and retroperitoneal adipocytes tended to be positively corelated (r = 0.24; P = .09 and r = 0.26; P = .07, n = 49, respectively) to the AUC and are indexes of adiposity. Results suggest that maintenance of retroperitoneal adipocytes at appropriate diameters may control progression of metabolic syndrome symptoms such as glucose tolerance.     

Green tea,black tea,and epigallocatechin modify body composition,improve glucose tolerance,and differentially alter metabolic gene expression in rats fed a high-fat diet

The mechanisms of how tea and epigallocatechin-3-gallate (EGCG) lower body fat are not completely understood. This study investigated long-term administration of green tea (GT), black tea (BT), or isolated EGCG (1 mg/kg per day) on body composition, glucose tolerance, and gene expression related to energy metabolism and lipid homeostasis; it was hypothesized that all treatments would improve the indicators of metabolic syndrome. Rats were fed a 15% fat diet for 6 months from 4 weeks of age and were supplied GT, BT, EGCG, or water. GT and BT reduced body fat, whereas GT and EGCG increased lean mass. At 16 weeks GT, BT, and EGCG improved glucose tolerance. In the liver, GT and BT increased the expression of genes involved in fatty acid synthesis (SREBP-1c, FAS, MCD, ACC) and oxidation (PPAR-α, CPT-1, ACO); however, EGCG had no effect. In perirenal fat, genes that mediate adipocyte differentiation were suppressed by GT (Pref-1, C/EBP-β, and PPAR-γ) and BT (C/EBP-β), while decreasing LPL, HSL, and UCP-2 expression; EGCG increased expression of UCP-2 and PPAR-γ genes. Liver triacylglycerol content was unchanged. The results suggest that GT and BT suppressed adipocyte differentiation and fatty acid uptake into adipose tissue, while increasing fat synthesis and oxidation by the liver, without inducing hepatic fat accumulation. In contrast, EGCG increased markers of thermogenesis and differentiation in adipose tissue, while having no effect on liver or muscle tissues at this dose. These results show novel and separate mechanisms by which tea and EGCG may improve glucose tolerance and support a role for these compounds in obesity prevention.     

Systematic review of saturated fatty acids on inflammation and circulating levels of adipokines

Diet is one factor that plays a part in coronary heart disease risk through multiple biological mechanisms including subclinical inflammation. In this review, we aimed to systematically assess and summarize evidence regarding the association of saturated fatty acids (SFAs) with inflammatory markers and adipokines. An electronic search of the literature was conducted up to September 2010 using Medline, Scopus, Web of Science, and Science Direct (updated from September 2010 to August 2011 through Medline). Original studies that were written in Portuguese, English, Spanish, or French, and addressed the effects of SFA (not dietary sources or SFA-rich diets) on inflammatory markers or adipokines in adult populations were considered eligible. Data from 15 studies providing adjusted estimates were extracted. The publication year varied from 1995 to 2010 and the sample size from 54 to 4900. Most studies were cross sectional, with 3 studies using a prospective design. Twelve studies assessed total SFA, and 3 studies considered their subtypes, which were measured through dietary assessments (11 studies) or in blood samples (4 studies). Significant positive associations were observed between SFA and soluble intercellular adhesion molecule-1 and interleukin-6, whereas no significant associations were observed with E-selectin, tumor necrosis factor α, granulocyte-macrophage colony-stimulating factor, fibrinogen, and adiponectin. For high-sensitivity C-reactive protein, 2 studies showed significant positive associations, whereas 3 studies reported no significant associations. One study reported a significant inverse association of SFA with leptin, although the other 3 found no significant associations. Based on this systematic review, a potential positive association of SFA with high-sensitivity C-reactive protein but not with adipokines is suggested, which should be confirmed by future research.     

Dietary intervention with vitamin D,calcium, and whey protein reduced fat mass and increased lean mass in rats

The aim of the current study was to determine the effects and the mechanisms of inclusion of dietary whey protein, high calcium, and high vitamin D intake with either a high-sucrose or high-fat base diets on body composition of rodents. Male Wistar rats were assigned to either no whey protein, suboptimal calcium (0.25%), and vitamin D (400 IU/kg) diet (LD), or a diet containing whey protein, high calcium (1.5%), and vitamin D (10 000 IU/kg) diet (HD), and either high-fat (40% of energy) or high-sucrose (60%) base diets for 13 weeks. Liver tissue homogenates were used to determine [¹⁴C]glucose and [¹⁴C]palmitate oxidation. mRNA expression of enzymes related to energy metabolism in liver, adipose, and muscle, as well as regulators of muscle mass and insulin receptor was assessed. The results demonstrated that there was reduced accumulation of body fat mass (P = .01) and greater lean mass (P = .03) for the HD- compared to LD-fed group regardless of the background diet. There were no consistent differences between the LD and HD groups across background diets in substrate oxidation and mRNA expression for enzymes measured that regulate energy metabolism, myostatin, or muscle vascular endothelial growth factor. However, there was an increase in insulin receptor mRNA expression in muscle in the HD compared to the LD groups. In conclusion, elevated whey protein, calcium, and vitamin D intake resulted in reduced accumulation of body fat mass and increased lean mass, with a commensurate increase in insulin receptor expression, regardless of the level of calories from fat or sucrose.     

Green tea extract reduces blood pressure,inflammatory biomarkers,and oxidative stress and improves parameters associated with insulin resistance in obese,hypertensive patients

Green tea (GT) consumption is known to be associated with enhanced cardiovascular and metabolic health. The purpose of this study is to examine the hypothesis that supplementation with GT alters insulin resistance and associated cardiovascular risk factors in obese, hypertensive patients. In a double-blind, placebo-controlled trial, 56 obese, hypertensive subjects were randomized to receive a daily supplement of 1 capsule that contained either 379 mg of GT extract (GTE) or a matching placebo, for 3 months. At baseline and after 3 months of treatment, the anthropometric parameters, blood pressure, plasma lipid levels, glucose levels, creatinine levels, tumor necrosis factor α levels, C-reactive protein levels, total antioxidant status, and insulin levels were assessed. Insulin resistance was evaluated according to the homeostasis model assessment–insulin resistance protocol. After 3 months of supplementation, both systolic and diastolic blood pressures had significantly decreased in the GTE group as compared with the placebo group (P < .01). Considerable (P < .01) reductions in fasting serum glucose and insulin levels and insulin resistance were observed in the GTE group when compared with the placebo group. Serum tumor necrosis factor α and C-reactive protein were significantly lower, whereas total antioxidant status increased in the GTE group compared with the placebo (P < .05). Supplementation also contributed to significant (P < .05) decreases in the total and low-density lipoprotein cholesterol and triglycerides, but an increase in high-density lipoprotein cholesterol. In conclusion, daily supplementation with 379 mg of GTE favorably influences blood pressure, insulin resistance, inflammation and oxidative stress, and lipid profile in patients with obesity-related hypertension.     

Fructose consumption during pregnancy and lactation induces fatty liver and glucose intolerance in rats

Nutritional insults during pregnancy and lactation are health risks for mother and offspring. Both fructose (FR) and low-protein (LP) diets are linked to hepatic steatosis and insulin resistance in nonpregnant animals. We hypothesized that dietary FR or LP intake during pregnancy may exacerbate the already compromised glucose homeostasis to induce gestational diabetes and fatty liver. Therefore, we investigated and compared the effects of LP or FR intake on hepatic steatosis and insulin resistance in unmated controls (CTs) and pregnant and lactating rats. Sprague-Dawley rats were fed a CT, or a 63% FR, or an 8% LP diet. Glucose tolerance test at day 17 of the study revealed greater (P < .05) blood glucose at 10 (75.6 mg/dL vs 64.0 ± 4.8 mg/dL) minutes and 20 (72.4 mg/dL vs 58.6 ± 4.0 mg/dL) minutes after glucose dose and greater area under the curve (4302.3 mg?dL^− 1? min^− 1 vs 3763.4 ± 263.6 mg?dL^− 1? min^− 1) for FR-fed dams compared with CT-fed dams. The rats were euthanized at 21 days postpartum. Both the FR- and LP-fed dams had enlarged (P < .05) livers (9.3%, 7.1% body weight vs 4.8% ± 0.2% body weight) and elevated (P < .05) liver triacylglycerol (216.0, 130.0 mg/g vs 19.9 ± 12.6 mg/g liver weight) compared with CT-fed dams. Fructose induced fatty liver and glucose intolerance in pregnant and lactating rats, but not unmated CT rats. The data demonstrate a unique physiological status response to diet resulting in the development of gestational diabetes coupled with hepatic steatosis in FR-fed dams, which is more severe than an LP diet.     

Millet consumption decreased serum concentration of triglyceride and C-reactive protein but not oxidative status in hyperlipidemic rats

This study was undertaken to investigate the hypothesis that whole grain consumption would have beneficial effects on lipid profiles, antioxidant status, and the inflammation state of hyperlipidemic rats compared to those resulting from a white rice (WR) diet. Forty-week-old male Sprague-Dawley rats (n = 24) were fed a high-fat diet (188.3 kJ% energy as fat) for 8 weeks to induce hyperlipidemia and were then randomly divided into 4 groups (n = 6 each) that were fed diets containing WR (control), sorghum, foxtail millet (FM), or proso millet for the next 5 weeks. Blood lipid profiles, hepatic antioxidant parameters, and inflammation-related measurements were determined in all of the groups. The concentrations of serum triglycerides were significantly lower in the FM and proso millet groups compared to those of the WR and sorghum groups. The concentrations of serum total, high-density lipoprotein (HDL), and low-density lipoprotein (LDL)-cholesterol were significantly higher in the sorghum group than in the WR, FM, and proso millet groups. Hepatic catalase, superoxide dismutase, and glutathione activities, as well as thiobarbituric acid reactive substance levels were not significantly different between the groups. Levels of C-reactive protein were significantly lower in the FM group than in the WR, sorghum, and proso millet groups. Inhibitor κB-α was expressed in the liver cytosolic fraction, and nuclear translocation of nuclear factor-κB (p65) into the liver nucleus was blocked in all groups. In conclusion, FM and proso millet may prevent cardiovascular disease by reducing plasma triglycerides in hyperlipidemic rats; in contrast, sorghum increases total cholesterol, HDL-cholesterol, and LDL-cholesterol concentrations.     

Aqueous extract of tamarind seeds selectively increases glucose transporter-2, glucose transporter-4, and islets' intracellular calcium levels and stimulates β-cell proliferation resulting in improved glucose homeostasis in rats with streptozotocin-induced diabetes mellitus

Tamarindus indica Linn. has been in use for a long time in Asian food and traditional medicine for different diseases including diabetes and obesity. However, the molecular mechanisms of these effects have not been fully understood. In view of the multidimensional activity of tamarind seeds due to their having high levels of polyphenols and flavonoids, we hypothesized that the insulin mimetic effect of aqueous tamarind seed extract (TSE) might increase glucose uptake through improvement in the expression of genes of the glucose transporter (GLUT) family and sterol regulatory element-binding proteins (SREBP) 1c messenger RNA (mRNA) in the liver. Daily oral administration of TSE to streptozotocin (STZ)–induced (90 mg/kg intraperitoneally) type 2 diabetic male Wistar rats at different doses (120 and 240 mg/kg body weight) for 4 weeks showed positive correlation with intracellular calcium and insulin release in isolated islets of Langerhans. Tamarind seed extract supplementation significantly improved the GLUT-2 protein and SREBP-1c mRNA expression in the liver and GLUT-4 protein and mRNA expression in the skeletal muscles of diabetic rats. The elevated levels of serum nitric oxide (NO), glycosylated hemoglobin level (hemoglobin _A1c) and tumor necrosis factor α (TNF-α) decreased after TSE administration. Immunohistochemical findings revealed that TSE abrogated STZ-induced apoptosis and increased β-cell neogenesis, indicating its effect on islets and β-cell mass. In conclusion, it was found that the antidiabetic effect of TSE on STZ-induced diabetes resulted from complex mechanisms of β-cell neogenesis, calcium handling, GLUT-2, GLUT-4, and SREBP-1c. These findings show the scope for formulating a new herbal drug for diabetes therapy.     

An inhibitory effect of resveratrol in the mitotic clonal expansion and insulin signaling pathway in the early phase of adipogenesis

Resveratrol is known as a potent antiobesity compound that acts partly through inhibition of adipogenesis. However, the direct targets responsible for its antiadipogenic action are unclear. Our hypothesis is that resveratrol inhibits adipogenesis through modulation of mitotic clonal expansion (MCE) and cell signaling pathways in the early phase of differentiation. To test this, we examined the effects of resveratrol on MCE and insulin signaling pathway in the early phase of adipogenesis in murine preadipocytes. We observed that the antiadipogenic action of resveratrol is largely limited to the early phase of adipogenesis. Specifically, the presence of resveratrol in the first 24 hours of adipogenesis was required for its antiadipogenic effect. During the first 24 hours of adipogenesis, resveratrol impaired the progression of MCE by suppressing the cell cycle entry of preadipocytes to G2/M phase, and expression of cell cycle regulators cyclin A and cyclin-dependent kinase 2. Concomitantly, resveratrol inhibited insulin signaling pathway in the early phase of adipogenesis. Furthermore, we revealed an inhibitory effect of resveratrol on insulin receptor (IR) activity, and this is likely through a direct physical interaction between resveratrol and IR. The antiadipogenic effect of resveratrol is through inhibition of the MCE and IR-dependent insulin signaling pathway in the early phase of adipogenesis.     

Acute exposure to high-fat diets increases hepatic expression of genes related to cell repair and remodeling in female rats

High-fat diets (HFD) promote the development of both obesity and fatty liver disease through the up-regulation of hepatic lipogenesis. Insulin resistance, a hallmark of both conditions, causes dysfunctional fuel partitioning and increases in lipogenesis. Recent work has demonstrated that systemic insulin resistance occurs in as little as the first 72 hours of an HFD, suggesting the potential for hepatic disruption with HFD at this time point. The current study sought to determine differences in expression of lipogenic genes between sexes in 3-month-old male and female Long-Evans rats after 72 hours of a 40% HFD or a 17% fat (chow) diet. Owing to the response of estrogen on hepatic signaling, we hypothesized that a sexual dimorphic response would occur in the expression of lipogenic enzymes, inflammatory cytokines, apoptotic, and cell repair and remodeling genes. Both sexes consumed more energy when fed an HFD compared with their low fat–fed controls. However, only the males fed the HFD had a significant increase in body fat. Regardless of sex, HFD caused down-regulation of lipogenic and inflammatory genes. Interestingly, females fed an HFD had up-regulated expression of apoptotic and cell repair–related genes compared with the males. This may suggest that females are more responsive to the acute hepatic injury effects caused by HFDs. In summary, neither male nor female rats displayed disrupted hepatic metabolic pathways after 72 hours of the HFD treatment. In addition, female rats appear to have protection from increases in fat deposition, possibly due to increased caloric expenditure; male rats fed an HFD were less active, as demonstrated by distance traveled in their home cage.