Late effects of postnatal administration of monosodium glutamate on insulin action in adult rats

Early postnatal administration of monosodium glutamate (MSG) to rats induces obesity, hyperinsulinemia and hyperglycemia in adulthood, thus suggesting the presence of insulin resistance. We therefore investigated the effects of insulin on glucose transport and lipogenesis in adipocytes as well as insulin binding to specific receptors in the liver, skeletal muscle and fat tissues. An increase of plasma insulin, glucose and leptin levels was found in 3-month-old rats treated with MSG during the postnatal period. The attenuation of insulin stimulatory effect on glucose transport was observed in MSG-treated rats. Despite the lower basal and insulin-stimulated glucose uptake, the incorporation of glucose into lipids was significantly higher in MSG-treated rats, suggesting a shift in glucose metabolism towards lipid synthesis in fat tissue. Insulin binding to plasma membranes from the liver, skeletal muscle and adipocytes was decreased in MSG-treated rats. This is in agreement with the lower insulin effect on glucose transport in these animals. Furthermore, a decreased amount of GLUT4 protein was found in adipocytes from MSG-treated obese rats. The results demonstrated an attenuation of insulin effect on glucose transport due to a lower insulin binding and lower content of GLUT4 protein in MSG-treated rats. However, the effect of insulin on lipogenesis was not changed. Our results indicated that early postnatal administration of MSG exerts an important effect on glucose metabolism and insulin action in adipocytes of adult animals.     

Taurine supplementation prevents morpho-physiological alterations in high-fat diet mice pancreatic β-cells

Taurine (Tau) is involved in beta (β)-cell function and insulin action regulation. Here, we verified the possible preventive effect of Tau in high-fat diet (HFD)-induced obesity and glucose intolerance and in the disruption of pancreatic β-cell morpho-physiology. Weaning Swiss mice were distributed into four groups: mice fed on HFD diet (36 % of saturated fat, HFD group); HTAU, mice fed on HFD diet and supplemented with 5 % Tau; control (CTL); and CTAU. After 19 weeks of diet and Tau treatments, glucose tolerance, insulin sensitivity and islet morpho-physiology were evaluated. HFD mice presented higher body weight and fat depots, and were hyperglycemic, hyperinsulinemic, glucose intolerant and insulin resistant. Their pancreatic islets secreted high levels of insulin in the presence of increasing glucose concentrations and 30 mM K⁺. Tau supplementation improved glucose tolerance and insulin sensitivity with a higher ratio of Akt phosphorylated (pAkt) related to Akt total protein content (pAkt/Akt) following insulin administration in the liver without altering body weight and fat deposition in HTAU mice. Isolated islets from HTAU mice released insulin similarly to CTL islets. HFD intake induced islet hypertrophy, increased β-cell/islet area and islet and β-cell mass content in the pancreas. Tau prevented islet and β-cell/islet area, and islet and β-cell mass alterations induced by HFD. The total insulin content in HFD islets was higher than that of CTL islets, and was not altered in HTAU islets. In conclusion, for the first time, we showed that Tau enhances liver Akt activation and prevents β-cell compensatory morpho-functional adaptations induced by HFD.     

镁补充对2 型糖尿病大鼠糖脂代谢的影响

目的:研究镁补充对2型糖尿病大鼠糖脂代谢的影响。方法:将用高脂饮食联合链脲佐菌素(STZ)方法诱发的2型糖尿病大鼠随机分为四个组,糖尿病对照组喂饲高脂饲料,高、中、低剂量组在高脂饲料中分别加入2000、1000、200 mg/kg的镁(以镁离子计)。自由饮食喂养四周,处死动物。用放射免疫法测血清胰岛素(Ins)水平、用葡萄糖氧化酶法测空腹血浆葡萄糖(fasting plasmaglucose,FPG),并计算胰岛素敏感指数(insulin sensitivity index,ISI)。比色法检测糖化血红蛋白(glycosylated hemoglobin,HbA1c)。用全自动生化分析仪测高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDLC)、甘油三酯(triglyceride,TG)、总胆固醇(total cholesterol,TC)。结果:高剂量组的空腹血糖、空腹血清、糖化血红蛋白、甘油三酯、总胆固醇水平均较糖尿病对照组显著性降低(P<0.05),而高密度脂蛋白胆固醇、胰岛素敏感指数较糖尿病对照组显著性升高(P<0.05)。结论:镁补充可以提高2型糖尿病大鼠胰岛素敏感性,改善糖尿病大鼠的糖脂代谢情况。     

Taurine supplementation restores glucose and carbachol-induced insulin secretion in islets from low-protein diet rats: involvement of Ach-M3R, Synt 1 and SNAP-25 proteins

Isolated islets from low-protein (LP) diet rats showed decreased insulin secretion in response to glucose and carbachol (Cch). Taurine (TAU) increases insulin secretion in rodent islets with a positive effect upon the cholinergic pathway. Here, we investigated the effect of TAU administration upon glucose tolerance and insulin release in rats fed on a normal protein diet (17%) without (NP) or with 2.5% of TAU in their drinking water (NPT), and LP diet fed rats (6%) without (LP) or with TAU (LPT). Glucose tolerance was found to be higher in LP, compared to NP rats. However, plasma glucose levels, during ipGTT, in LPT rats were similar to those of controls. Isolated islets from LP rats secreted less insulin in response to increasing glucose concentrations (2.8-22.2 mmol/L) and to 100 μmol/L Cch. This lower secretion was accompanied by a reduction in Cch-induced internal Ca(2+) mobilization. TAU supplementation prevents these alterations, as judged by the higher secretion induced by glucose or Cch in LPT islets. In addition, Ach-M3R, syntaxin 1 and synaptosomal associated protein of 25 kDa protein expressions in LP were lower than in NP islets. The expressions of these proteins in LPT were normalized. Finally, the sarcoendoplasmatic reticulum Ca(2+)-ATPase 3 protein expression was higher in LPT and NPT, compared with controls. In conclusion, TAU supplementation to LP rats prevented alterations in glucose tolerance as well as in insulin secretion from isolated islets. The latter effect involves the normalization of the cholinergic pathway, associated with the preservation of exocytotic proteins.     

Appearance and metabolic development of diabetes mellitus in the sand rat, Psammomys obesus

The aim of this study was to examine the long-term effects of synthetic chow diet on the metabolic pattern of diabetic syndrome in a large group of sand rats. Few animals had a fulminating reaction with markedly decreased glucose tolerance, low plasma insulin levels and death within 3-4 weeks. But the most of sand rats developed obesity and elevated plasma insulin levels. From the third month, 40% of sand rats presented a diabetic syndrome with hyperinsulinemia, hyperglycemia, markedly decreased glucose tolerance and insulin resistance. Plasma lipids were increased; the lipid and glycogen accumulation in the liver was high. So this diabetic syndrome can be compared to maturity onset diabetes. If this synthetic chow diet lasted more than 6 months, the most of animals lost considerable weight with a strong lipid depletion of fat stores. Serum immunoreactive insulin levels fall and the blood glucose rose over 500 mg/100 ml with glycosuria and ketonuria . The elevated triglyceride content of plasma and the lipid deposits in the liver were exaggerated; glycogen had disappeared. Animals developed an overtly insulin- dependent diabetes, the latter phase of the disease. The sand rat appears to us as a potentially interesting model for investigation both maturity onset and ketotic-type diabetic syndrome.     

Protective effect of esculetin on hyperglycemia-mediated oxidative damage in the hepatic and renal tissues of experimental diabetic rats

Diabetes mellitus is the most common serious metabolic disorder and it is considered to be one of the five leading causes of death in the world. Hyperglycemia-mediated oxidative stress plays a crucial role in diabetic complications. Hence, this study was undertaken to evaluate the protective effect of esculetin on the plasma glucose, insulin levels, tissue antioxidant defense system and lipid peroxidative status in streptozotocin-induced diabetic rats. Diabetic rats exhibited increased blood glucose with significant decrease in plasma insulin levels. Extent of oxidative stress was assessed by the elevation in the levels of lipid peroxidation markers such as thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (HP) and conjugated dienes (CD); reduction in the enzymic antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST); nonenzymic antioxidants Vitamin C, E and reduced glutathione (GSH) were observed in the liver and kidney tissues of diabetic control rats as compared to control rats. Oral supplementation of esculetin to diabetic rats for 45 days significantly brought back lipid peroxidation markers, enzymic and nonenzymic antioxidants to near normalcy. Moreover, the histological observations evidenced that esculetin effectively rescues the hepatocytes and kidney from hyperglycemia mediated oxidative damage without affecting its cellular function and structural integrity. These findings suggest that esculetin (40 mg/kg BW) treatment exerts a protective effect in diabetes by attenuating hyperglycemia-mediated oxidative stress and antioxidant competence in hepatic and renal tissues. Further, detailed studies are in progress to elucidate the molecular mechanism by which esculetin elicits its modulatory effects in insulin signaling pathway.     

Impaired muscarinic type 3 (M3) receptor/PKC and PKA pathways in islets from MSG-obese rats

Monosodium glutamate-obese rats are glucose intolerant and insulin resistant. Their pancreatic islets secrete more insulin at increasing glucose concentrations, despite the possible imbalance in the autonomic nervous system of these rats. Here, we investigate the involvement of the cholinergic/protein kinase (PK)-C and PKA pathways in MSG β-cell function. Male newborn Wistar rats received a subcutaneous injection of MSG (4 g/kg body weight (BW)) or hyperosmotic saline solution during the first 5 days of life. At 90 days of life, plasma parameters, islet static insulin secretion and protein expression were analyzed. Monosodium glutamate rats presented lower body weight and decreased nasoanal length, but had higher body fat depots, glucose intolerance, hyperinsulinemia and hypertrigliceridemia. Their pancreatic islets secreted more insulin in the presence of increasing glucose concentrations with no modifications in the islet-protein content of the glucose-sensing proteins: the glucose transporter (GLUT)-2 and glycokinase. However, MSG islets presented a lower secretory capacity at 40 mM K⁺ (P < 0.05). The MSG group also released less insulin in response to 100 μM carbachol, 10 μM forskolin and 1 mM 3-isobutyl-1-methyl-xantine (P < 0.05, P < 0.0001 and P < 0.01). These effects may be associated with a the decrease of 46 % in the acetylcholine muscarinic type 3 (M3) receptor, and a reduction of 64 % in PKCα and 36 % in PKAα protein expressions in MSG islets. Our data suggest that MSG islets, whilst showing a compensatory increase in glucose-induced insulin release, demonstrate decreased islet M3/PKC and adenylate cyclase/PKA activation, possibly predisposing these prediabetic rodents to the early development of β-cell dysfunction.     

Tesaglitazar, a dual PPAR{alpha}/{gamma} agonist, ameliorates glucose and lipid intolerance in obese Zucker rats

Insulin resistance, impaired glucose tolerance, high circulating levels of free fatty acids (FFA), and postprandial hyperlipidemia are associated with the metabolic syndrome, which has been linked to increased risk of cardiovascular disease. We studied the metabolic responses to an oral glucose/triglyceride (TG) (1.7/2.0 g/kg lean body mass) load in three groups of conscious 7-h fasted Zucker rats: lean healthy controls, obese insulin-resistant/dyslipidemic controls, and obese rats treated with the dual peroxisome proliferator-activated receptor alpha/gamma agonist, tesaglitazar, 3 mumol.kg(-1).day(-1) for 4 wk. Untreated obese Zucker rats displayed marked insulin resistance, as well as glucose and lipid intolerance in response to the glucose/TG load. The 2-h postload area under the curve values were greater for glucose (+19%), insulin (+849%), FFA (+53%), and TG (+413%) compared with untreated lean controls. Treatment with tesaglitazar lowered fasting plasma glucose, improved glucose tolerance, substantially reduced fasting and postload insulin levels, and markedly lowered fasting TG and improved lipid tolerance. Fasting FFA were not affected, but postprandial FFA suppression was restored to levels seen in lean controls. Mechanisms of tesaglitazar-induced lowering of plasma TG were studied separately using the Triton WR1339 method. In anesthetized, 5-h fasted, obese Zucker rats, tesaglitazar reduced hepatic TG secretion by 47%, increased plasma TG clearance by 490%, and reduced very low-density lipoprotein (VLDL) apolipoprotein CIII content by 86%, compared with obese controls. In conclusion, the glucose/lipid tolerance test in obese Zucker rats appears to be a useful model of the metabolic syndrome that can be used to evaluate therapeutic effects on impaired postprandial glucose and lipid metabolism. The present work demonstrates that tesaglitazar ameliorates these abnormalities and enhances insulin sensitivity in this animal model.     

Comparison of high-protein diets and leucine supplementation in the prevention of metabolic syndrome and related disorders in mice

High-protein diets have been shown to promote weight loss, to improve glucose homeostasis and to increase energy expenditure and fat oxidation. We aimed to study whether leucine supplementation is able to mimic the alleviating effects of high-protein diets on metabolic syndrome parameters in mice fed high-fat diet.Male C57BL/6 mice were fed for 20 weeks with semisynthetic high-fat diets (20% w/w of fat) containing either an adequate (10% protein, AP) or high (50% protein, HP) amount of whey protein, or an AP diet supplemented with l-leucine corresponding to the leucine content of the HP diet (6% leucine, AP+L). Body weight and composition, energy expenditure, glucose tolerance, hepatic triacylglycerols (TG), plasma parameters as well as expression levels of mRNA and proteins in different tissues were measured. HP feeding resulted in decreased body weight, body fat and hepatic TG accumulation, as well as increased insulin sensitivity compared to AP. This was linked to an increased total and resting energy expenditure (REE), decreased feed energy efficiency, increased skeletal muscle (SM) protein synthesis, reduced hepatic lipogenesis and increased white fat lipolysis. Leucine supplementation had effects that were intermediate between HP and AP with regard to body composition, liver TG content, insulin sensitivity, REE and feed energy efficiency, and similar effects as HP on SM protein synthesis. However, neither HP nor AP+L showed an activation of the mammalian target of rapamycin pathway in SM. Leucine supplementation had no effect on liver lipogenesis and white fat lipolysis compared to AP. It is concluded that the essential amino acid leucine is able to mimic part but not all beneficial metabolic effects of HP diets.     

大脑胰岛素信号途径受损导致2型糖尿病时阿尔茨海默病发病风险增高

大脑胰岛素不仅可调节血糖,而且可改善记忆和认知,而大脑胰岛素缺乏常导致Alzheimer病（Alzheimer’s disease, AD）的发生. 本研究检测了正常及2型糖尿病（type 2 diabetes, T2D）大鼠外周及大脑胰岛素信号传导途径,以探讨T2D时由于大脑胰岛素异常导致AD发病的可能性.以同龄正常SD大鼠为对照（CTL组）,高糖、高脂、高蛋白饮食加链脲佐菌素（streptozotocin, STZ）腹腔注射建造T2D大鼠模型（T2D组）.葡萄糖氧化酶法检测血浆血糖,放免法检测脑脊液及血浆胰岛素,免疫印迹技术检测大脑海马tau蛋白上部分位点磷酸化水平,大脑及肝脏、肌肉组织胰岛素信号传导途径中磷脂酰肌醇3 激酶（phosphatidylinositol 3 kinase, PI3K）/ 蛋白激酶B（protein kinase B,Akt)、糖原合成激酶3β（glycogen synthase kinase 3β, GSK 3β）活性. 结果显示：和对照组相比,T2D大鼠血浆葡萄糖水平及胰岛素水平显著升高,脑脊液胰岛素水平显著降低,大脑海马组织tau蛋白上所检测位点均呈过度磷酸化改变,海马及外周组织（肝脏、肌肉）胰岛素信号传导途径PI3K/Akt活性均显著下降,GSK 3β活性升高. 研究结果表明：2型糖尿病大鼠大脑胰岛素缺乏及其信号传导途径下调可能是导致阿尔茨海默病发病的重要原因.     

Effect of high-intensity exercise and high-fat diet on lipid metabolism in the liver of rats

[Purpose]

This study investigated the effects of high-intensity exercise (Ex) and high dietary fat intake on lipid metabolism in the liver of rats.

[Methods]

Male Sprague-Dawley rats were randomly assigned to one of the four groups (n=10 per group) that were maintained on a normal diet (ND) or high-fat diet (HFD) consisting of 30% fat (w/w), with or without exercise on a treadmill at 30 m/min and 8% grade) for 4 weeks (i.e., ND, ND+Ex, HFD, and HFD+Ex groups).

[Results]

Body weight (p<.001), total plasma cholesterol (TC) (p<.001), triglyceride (TG) (p<.05), and liver TG levels (p<.05) were increased in the HFD group relative to the ND groups, and serum glucose (p<.05), insulin (p<.05), homeostatic model assessment of insulin resistance (HOMA-IR) (p<.01), and liver TG levels (p<.01) were also higher in the HFD group compared to the ND+Ex group. Plasma free fatty acid was elevated in the HFD+Ex group compared to the HFD group (p<.01). With the exception of acetyl coenzyme A carboxylase, the expression of lipid metabolism-related genes in the liver was altered in the Ex groups compared to the control group (p<.05), with genes involved in lipolysis specifically up regulated in the HFD+Ex group compared to the other groups.

[Conclusion]

Vigorous exercise may increase glucose utilization and fat oxidation by activating genes in the liver that are associated with lipid metabolism compared to that in animals consuming a HFD without exercise. Therefore, high intensity exercise can be considered to counter the adverse effects of high dietary fat intake.     

The effect of dietary polyunsaturated fatty acid on insulin sensitivity and lipid metabolism in Otsuka Long-Evans Tokushima Fatty (OLETF) rats

The effects of insulin sensitivity and lipid metabolism of dietary lard, eicosapentaenoic acid-rich oil (EPA oil) or arachidonic acid oil (AA oil) in Otsuka Long-Evans Tokushima Fatty (OLETF) rats were examined. Blood glucose was not different in each group at 30, 60, 120 min on an oral glucose tolerance test. Fasting blood glucose levels were lower in lard and AA oil groups than in controls. Hepatic triglyceride concentration and liver histochemistry revealed that the fat content was higher in the lard group and the AA oil group than in controls. The EPA oil group showed TG levels as high as the control group. Serum total cholesterol in the EPA oil group was lower, while the level in the AA oil group was higher than in the lard and control groups. HDL cholesterol was 1.5-fold higher in the AA oil group than in controls. Dietary EPA oil or AA oil supplementation showed different effects on lipid metabolism in this model.     

Fish oil supplementation in F1 generation associated with naproxen, clenbuterol, and insulin administration reduce tumor growth and cachexia in Walker 256 tumor-bearing rats

Weanling female Wistar rats were supplemented with fish oil (1 g/kg body weight) for one generation. The male offspring received the same supplementation until to adult age. Rats supplemented with coconut fat were used as reference. Some rats were inoculated subcutaneously with a suspension (2 x 10(7) cells/mL) of Walker 256 tumor. At day 3, when the tumor was palpable, rats were treated with naproxen (N) (0.1 mg/mL), clenbuterol (Cb) (0.15 mg/kg body weight), and insulin (I) (10 U/kg body weight). At day 14 after tumor inoculation, the animals were killed. Tumor was removed and weighed. Blood, liver, and skeletal muscles were also collected for measurements of metabolites and insulin. In both tumor-bearing untreated rats and tumor-bearing rats supplemented with coconut fat, tumor growth, triacylglycerol, and blood lactate levels were higher, and glycogen content of the liver, blood glucose, cholesterol and HDL-cholesterol levels were lower as compared with the non-tumor-bearing and fish oil supplemented groups. Fish oil supplementation of tumor-bearing rats led to a partial recovery of the glycogen content in the liver and a full reversion of blood glucose, lactate, cholesterol, and HDL-cholesterol levels. The treatment with N plus Cb plus I attenuated cancer cachexia and decreased tumor growth in both coconut fat and fish oil supplemented rats. In conclusion, chronic fish oil supplementation decreased tumor growth and partially recovered cachexia. This beneficial effect of fish oil supplementation was potentiated by treatment with naproxen plus clenbuterol plus insulin.     

阿司匹林增加胰岛素抵抗大鼠胰岛素敏感性的实验研究

目的　观察阿司匹林对高脂饮食大鼠胰岛素敏感性的影响。方法　灌服阿司匹林前后采用腹腔注射胰岛素耐量试验 (IITT)观察大鼠胰岛素的敏感性 ,并测定空服胰岛素、血糖和血脂等。结果　高脂饮食 4月、阿司匹林治疗 4周后 ,IITT发现高脂组腹腔注射胰岛素后 1h、1 5h和 2h的血糖及空腹胰岛素和甘油三酯水平显著高于正常对照组 (P <0 0 5或P <0 0 1 ) ;而阿司匹林治疗组腹腔注射胰岛素后 1h、1 5h和 2h的血糖及空腹胰岛素和甘油三酯水平显著低于高脂组 (P <0 0 5或P <0 0 1 ) ,与正常对照组差异无显著性。结论　大剂量阿司匹林有增加胰岛素敏感性和改善脂代谢紊乱的作用     

Angiotensin II type 1 receptor blocker ameliorates overproduction and accumulation of triglyceride in the liver of Zucker fatty rats

The effects of angiotensin II type 1 receptor blocker (ARB) on triglyceride (TG) metabolism associated with insulin resistance were explored in Zucker fatty (ZF) rats. Olmesartan medoxomil, a newly developed ARB, was given as a 0.01% drinking solution ad libitum to ZF and Zucker lean (ZL) rats for 4 wk. Olmesartan lowered blood pressure in both strains to the same extent. ZF rats had a markedly low insulin sensitivity index (SI) and glucose effectiveness (SG), together with significantly increased glucose levels. Olmesartan treatment substantially elevated both SI and SG. The ZF rats were hyperlipidemic, with plasma TG levels sixfold higher than those of the ZL rats. Olmesartan remarkably decreased the plasma free fatty acid level in the ZF rats, but it did not exert a significant effect on the plasma TG level. The TG secretion rate assessed by the Triton WR-1339 technique was almost six times higher in the ZF than in the ZL rats, and olmesartan treatment suppressed this TG overproduction by one-half. The TG content in the liver was ten times higher in the ZF than in the ZL rats, and olmesartan halved this high hepatic TG content without affecting the cholesterol content. The fatty liver developed in the ZF rats was ameliorated by olmesartan treatment. Olmesartan treatment had no significant effects on TG metabolism or insulin sensitivity in the ZL rats. Taken in sum, ARB improves the overproduction and accumulation of TG in the liver associated with insulin resistance, and it does so through mechanisms independent of its hypotensive action.     

Efficacy of azelaic acid on hepatic key enzymes of carbohydrate metabolism in high fat diet induced type 2 diabetic mice

Azelaic acid (AzA), a C9 linear α,ω-dicarboxylic acid, is found in whole grains namely wheat, rye, barley, oat seeds and sorghum. The study was performed to investigate whether AzA exerts beneficial effect on hepatic key enzymes of carbohydrate metabolism in high fat diet (HFD) induced type 2 diabetic C57BL/6J mice. C57BL/6J mice were fed high fat diet for 10 weeks and subjected to intragastric administration of various doses (20 mg, 40 mg and 80 mg/kg BW) of AzA daily for the subsequent 5 weeks. Rosiglitazone (RSG) was used as reference drug. Body weight, food intake, plasma glucose, plasma insulin, blood haemoglobin (Hb), blood glycosylated haemoglobin (HbA1c), liver glycolytic enzyme (hexokinase), hepatic shunt enzyme (glucose-6-phosphate dehydrogenase), gluconeogenic enzymes(glucose-6-phosphatase and fructose-1,6-bisphosphatase), liver glycogen, plasma and liver triglycerides were examined in mice fed with normal standard diet (NC), high fat diet (HFD), HFD with AzA (HFD + AzA) and HFD with rosiglitazone (HFD + RSG). Among the three doses, 80 mg/kg BW of AzA was able to positively regulate plasma glucose, insulin, blood HbA1c and haemoglobin levels by significantly increasing the activity of hexokinase and glucose-6-phosphate dehydrogenase and significantly decreasing the activity of glucose-6-phosphatase and fructose-1,6-bisphosphatase thereby increasing the glycogen content in the liver. From this study, we put forward that AzA could significantly restore the levels of plasma glucose, insulin, HbA1c, Hb, liver glycogen and carbohydrate metabolic key enzymes to near normal in diabetic mice and hence, AzA may be useful as a biomaterial in the development of therapeutic agents against high fat diet induced T2DM.     

The interaction effects of aerobic exercise training and vitamin D supplementation on plasma lipid profiles and insulin resistance in ovariectomized rats

Purpose

The purpose of this study was to determine the interaction effects of aerobic exercise training and vitamin D supplementation on indices of obesity and plasma lipid profiles in ovariectomized (OVX) rats.

Methods

Forty female Wistar rats were divided into 5 groups: aerobic training (3 days/week for 8 weeks; AT; n = 8), aerobic training and vitamin D supplementation (OVX + AT + Vit D; n = 8), vitamin D supplementation (OVX + Vit D; n = 8), ovariectomized control (OVX + C, n = 8) and SHAM (n = 8). After blood sampling, visceral fat was taken from the abdominal cavity and weighed immediately. Data was statistically analyzed by One-way ANOVA and Repeated measure ANOVA tests with a 0.05 significance level.

Results

Body weight, visceral fat, BMI and food intake decreased significantly in OVX + AT + Vit D (P < 0.001); whereas these variables increased significantly in OVX + C (P < 0.001) and SHAM (P < 0.023) groups. At the end of two-months of follow-up, we observed significant differences in TC, TG, HDL-C, LDL-C, glucose, insulin, and HOMA-IR in all groups.

Conclusion

It seems that aerobic training with vitamin D, due to the involvement of muscle mass and exposure to dynamic pressure on the bones and muscles, increased energy expenditure, stimulated insulin exudation and glucose homeostasis, decreased insulin resistance and improved the lipid profile in ovariectomized rats.     

Excessive Energy Intake Does Not Modify Fed‐state Tissue Protein Synthesis Rates in Adult Rats

The impact of chronic excessive energy intake on protein metabolism is still controversial. Male Wistar rats were fed ad libitum during 5 weeks with either a high‐fat high‐sucrose diet (HF: n = 9) containing 45% of total energy as lipids (protein 14%; carbohydrate 40% with 83.5% sucrose) or a standard diet (controls: n = 10). Energy intake and body weight were recorded. At the end of the experiment, we measured body composition, metabolic parameters (plasma amino acid, lipid, insulin, and glucose levels), inflammatory parameter (plasma α2‐macroglobulin), oxidative stress parameters (antioxidant enzyme activities, lipoperoxidation (LPO), protein carbonyl content in liver and muscle), and in vivo fed–state fractional protein synthesis rates (FSRs) in muscle and liver. Energy intake was significantly higher in HF compared with control rats (+28%). There were significant increases in body weight (+8%), body fat (+21%), renal (+41%), and epidydimal (+28%) fat pads in HF compared with control rats. No effect was observed in other tissue weights (liver, muscle, spleen, kidneys, intestine). Liver and muscle FSRs, plasma levels of lipids, glucose, insulin and α2‐macroglobulin, soleus and liver glutathione reductase and peroxidase acitivities, MnSOD activity, LPO, and protein carbonyl content were not altered by the HF diet. Only soleus muscle and liver Cu/ZnSOD activity and soleus muscle catalase activities were reduced in HF rats compared with control rats. Thus, chronic excessive energy intake and increased adiposity, in the absence of other metabolic alterations, do not stimulate fed‐state tissue protein synthesis rates.     

Comparison of the Relative Contributions of Intra‐Abdominal and Liver Fat to Components of the Metabolic Syndrome

Abdominally obese individuals with the metabolic syndrome often have excess fat deposition both intra‐abdominally (IA) and in the liver, but the relative contribution of these two deposits to variation in components of the metabolic syndrome remains unclear. We determined the mutually independent quantitative contributions of IA and liver fat to components of the syndrome, fasting serum (fS) insulin, and liver enzymes and measures of hepatic insulin sensitivity in 356 subjects (mean age 42 years, mean BMI 29.7 kg/m²) in whom liver fat and abdominal fat volumes were measured. IA and liver fat contents were correlated (r = 0.65, P < 0.0001). In multivariate linear regression analyses including either liver or IA fat, liver fat or IA fat explained variation in fS‐triglyceride (TG) and high‐density lipoprotein (HDL) cholesterol, plasma glucose, insulin and liver enzyme concentrations, and hepatic insulin sensitivity independent of age, gender, subcutaneous (SC) fat, and/or lean body mass (LBM). Including both liver and IA fat, liver and IA fat both explained variation in TG, HDL cholesterol, insulin and hepatic insulin sensitivity independent of each other and of age, gender, SC fat, and LBM. Liver fat independently predicted glucose and liver enzymes. SC fat and age explained variation in blood pressure. In conclusion, both IA and liver fat independently of each other explain variation in serum TG, HDL cholesterol, insulin concentrations and hepatic insulin sensitivity, thus supporting that both fat depots are important predictors of these components of the metabolic syndrome.     

Fucoxanthin supplementation improves plasma and hepatic lipid metabolism and blood glucose concentration in high-fat fed C57BL/6N mice

This study investigated the effects of fucoxanthin isolated from marine plant extracts on lipid metabolism and blood glucose concentration in high-fat diet fed C57BL/6N mice. The mice were divided into high-fat control (HFC; 20% fat, w/w), low-fucoxanthin (low-Fxn; HFC + 0.05% Fxn, w/w) and high-fucoxanthin (high-Fxn; HFC + 0.2% Fxn, w/w) groups. Fxn supplementation significantly lowered the concentration of plasma triglyceride with a concomitant increase of fecal lipids in comparison to the HFC group. Also, the hepatic lipid contents were significantly lowered in the Fxn supplemented groups which seemed to be due to the reduced activity of the hepatic lipogenic enzymes, glucose-6-phosphate dehydrogenase, malic enzyme, fatty acid synthase and phosphatidate phosphohydrolase and the enhanced activity of β-oxidation. Plasma high-density lipoprotein cholesterol concentrations and its percentage were markedly elevated by Fxn supplementation. Activities of two key cholesterol regulating enzymes: 3-hydroxy-3-methylglutaryl coenzyme A reductase and acyl coenzyme A: cholesterol acyltransferase, were significantly suppressed by Fxn regardless of the dosage. Relative mRNA expressions of acyl-coA oxidase 1, palmitoyl (ACOX1) and peroxisome proliferators activated receptor α (PPARα) and γ (PPARγ) were significantly altered by Fxn supplementation in the liver. Fxn also lowered blood glucose and HbA_1c levels along with plasma resistin and insulin concentrations. These results suggest that Fxn supplementation plays a beneficial role in not only regulating the plasma and hepatic lipids metabolism but also for blood glucose-lowering action in high-fat fed mice.