Improvement of insulin resistance and insulin secretion by water extracts of Cordyceps militaris, Phellinus linteus, and Paecilomyces tenuipes in 90% pancreatectomized rats

The effect of supplementation with Phellinus linteus (P. linteus), Paecilomyces tenuipes (P. tenuipes), and Cordyceps militaris (C. militaris) mushroom water extracts on the insulin secretion and insulin resistance of 90% pancreatectomized (Px) male Sprague Dawley rats was investigated. Px rats were daily administered 0.5 g of P. linteus, P. tenuipes, and C. militaris aqueous extracts or a placebo per 1 kg body weight with a 40% fat diet for 8 weeks. Fasting serum glucose levels were lower in rats receiving C. militaris than in the control group. Insulin secretion at the elevated serum glucose levels was lowest in rats that consumed P. tenuipes in hyperglycemic clamp. Whole body glucose disposal rates increased in C. militaris but decreased in P. tenuipes compared to those in the control group in euglycemic hyperinsulinemic clamp. The GLUT4 content and fraction velocity of glycogen synthase in the soleus and quadriceps muscles increased in the rats treated with C. militaris, but P. tenuipes decreased both. In sum, a water extract of C. militaris ameliorates insulin resistance by enhancing glucose utilization in skeletal muscles.     

Effects of dietary D-psicose on diurnal variation in plasma glucose and insulin concentrations of rats

The effects of supplemental D-psicose in the diet on diurnal variation in plasma glucose and insulin concentrations were investigated in rats. Forty-eight male Wistar rats were divided into four groups. Each group except for the control group was fed a diet of 5% D-fructose, D-psicose, or psico-rare sugar (3:1 mixture of D-fructose and D-psicose) for 8 weeks. Plasma glucose levels were lower and plasma insulin levels were higher at all times of day in the psicose and psico-rare sugar groups than in the control and fructose groups. Weight gain was significantly lower in the psicose group than in the control and fructose groups. Liver glycogen content, both before and after meals was higher in the psicose group than in the control and fructose groups. These results suggest that supplemental D-psicose can lower plasma glucose levels and reduce body fat accumulation. Hence, D-psicose might be useful in preventing postprandial hyperglycemia in diabetic patients.     

Insulin and glucagon secretion and the insulin sensitivity of peripheric organs of colony-bred sand rats fed with pellet diet after weaning.

Colony-bred sand rats were fed with rat pellet chow in restricted quantities or ad libitum for 8--10 or 28--31 weeks after weaning. The changes of glucose metabolism were characterized by an intraperitoneal glucose tolerance test. The daily food intake and the average weight gain differed only in the first 5--7 weeks of pellet nutrition. In the impaired glucose tolerance tests of all sand rats the high basal plasma IRI levels were not significantly increased by the grossly enhanced blood glucose concentrations. The insulin secretion of either acutely incubated or for 8 days cultivated isolated pancreatic islets, however, was stimulated already by low (1.7 and 5 mM) glucose concentrations in all diet groups. Otherwise the glucagon secretion of isolated islets was not suppressed by high glucose concentrations. No changes of insulin or glucagon contents of islets were found in the different diet groups. The adipocytes of all animals revealed a complete ineffectiveness of insulin on the glucose utilization to CO2 and triglycerides. The basal glucose conversion to CO2 and glycogen in skeletal muscle and the stimulatory potency of insulin was low and not distinctly different in all groups. In liver glycogen and triglyceride contents as well as gluconeogenic enzyme activities were not influenced by feeding of different quantities of pellet diet at the investigated time points. The time course of the metabolic and clinical alterations demonstrates that the peripheral organs become insensitive to insulin in the first weeks after weaning.     

High multivitamin intake by Wistar rats during pregnancy results in increased food intake and components of the metabolic syndrome in male offspring

The effect of high multivitamin intake during pregnancy on the metabolic phenotype of rat offspring was investigated. Pregnant Wistar rats (n=10 per group) were fed the AIN-93G diet with the recommended vitamin (RV) content or a 10-fold increase [high vitamin (HV) content]. In experiment 1, male and female offspring were followed for 12 wk after weaning; in experiment 2, only males were followed for 28 wk. Body weight (BW) was measured weekly. Every 4 wk, after an overnight fast, food intake over 1 h was measured 30 min after a gavage of glucose or water. An oral glucose tolerance test was performed every 3-5 wk. Postweaning fasting glucose, insulin, ghrelin, glucagon-like peptide-1, and systolic blood pressure were measured. No difference in BW at birth or litter size was observed. Food intake was greater in males born to HV dams (P<0.05), and at 28 wk after weaning, BW was 8% higher (P<0.05) and fat pad mass was 27% higher (P<0.05). Food intake reduction after the glucose preload was nearly twofold less in males born to HV dams at 12 wk after weaning (P<0.05). Fasting glucose, insulin, and ghrelin were 11%, 62%, and 41% higher in males from HV dams at 14 wk after weaning (P<0.05). Blood glucose response was 46% higher at 23 wk after weaning (P<0.01), and systolic blood pressure was 16% higher at 28 wk after weaning (P<0.05). In conclusion, high multivitamin intake during pregnancy programmed the male offspring for the development of the components of metabolic syndrome in adulthood, possibly by its effects on central mechanisms of food intake control.     

Early exposure to a high-fat diet has more drastic consequences on metabolism compared with exposure during adulthood in rats

The aim of this study was determine whether the introduction of a high-fat diet during the peripubertal phase induces significant changes in body weight control, glucose homeostasis and the parasympathetic tonus compared with the administration of this diet to adult rats. High-fat diet was offered to male Wistar rats at weaning or during adulthood. A group of rats received high-fat diet for 60 days, from weaning to 81-day-old (HF81) or from 60 to 120-day-old (HF120), whereas 2 other groups received a normal-fat diet (i. e., NF81 and NF120). We analyzed adiposity, glucose homeostasis, insulin sensitivity, and vagal nerve activity. High-fat diet increased the accumulation of adipose tissue in all of the rats, but the difference was greater in the rats that were fed the high-fat diet since weaning (p<0.001). The HF rats showed glucose intolerance with high levels of insulin secretion during the glucose tolerance test (p<0.01). Rats that were fed the high-fat diet presented severe insulin resistance, indicated by a low K itt (p<0.01). Interestingly, the HF81 rats exhibited greater insulin resistance compared with the HF120 rats (p<0.05). The recordings of vagus nerve activity showed that the HF rats had higher parasympathetic activity than the NF rats irrespective of age (p<0.01). Our results show that a high-fat diet offered to rats just after weaning or in adulthood both cause impairment of glycemic homeostasis and imbalance in parasympathetic activity. Importantly, the consumption of high-fat diet immediately after weaning has more drastic consequences compared with the consumption of the same diet during adulthood.     

Study on the effect of a high fat diet on diaphragm and liver glycogen and glycerides in the rat

The present work was undertaken to study the effect of nutritional obesity induced by a high fat diet on the consumption of glycogen and glycerides in rat liver and diaphragm. Groups of rats were fed for five weeks from weaning either a fat-rich-carbohydrate (CHO)-poor diet, or a CHO-rich-fat-poor diet. Basal plasma glucose and free fatty acids (FFA) were significantly increased in the animals adapted to the fat-rich diet. Half of the rats were submitted to a 48-h fast. After fast, basal plasma glucose and immunoreactive insulin (IRI) fell significantly, whereas plasma FFA levels were higher than in the group fed the CHO-rich-fat-poor diet. In the liver, glycogen concentration fell in both groups after fast, with a glycogen breakdown of 1930 +/- 244 mumole glycogen glucose/liver in the fat-fed group vs 4636 +/- 216 mumole/liver in the CHO-fed group. Glycerides fell by 750 +/- 68 mumole glyceride glycerol/liver in the fat-fed rats while remaining unchanged (increased by 82 +/- 57 mumole/liver) in the CHO-fed group. In the diaphragm glycogen concentration also fell in both groups, with a glycogen breakdown of 6.0 +/- 0.3 mumole glycogen glucose/g wet tissue in the fat-fed rats vs 15.2 +/- 1.4 mumole/g wet tissue in the CHO-fed animals. Glycerides fell by 23.1 +/- 4.0 mumole/g wet diaphragm in the CHO-fed animals. The lower breakdown of glycogen in both liver and diaphragm of fat-fed rats demonstrates a decreased utilization of glycogen during fast, with energy consumption originating in larger part from triglycerides.(ABSTRACT TRUNCATED AT 250 WORDS)     

The significance of hyperphagia and diet composition on the metabolism in ventromedial hypothalamic lesioned male rats

The metabolic consequences of ventromedial hypothalamic lesion were studied in a group of aged male rats which were obese and had decreased response to insulin. The effects of hyperphagia and ventromedial hypothalamic lesion per se were separated by comparing experimental animals fed isocalorically with controls and animals fed ad libitum. Ventromedial hypothalamic lesion as such led to increases in the glucose conversion to fatty acid and in lipoprotein lipase activity in adipose tissue. Protein catabolism as reflected by plasma urea levels, was enhanced. The lipoprotein lipase activity in heart tended to be lower after VMH lesion. These metabolic changes were amplified in the VMH lesioned rats fed ad libitum. The liver glycogen content was lowered by VMH lesion, but this effect was abolished by hyperphagia. In parallel experiments the influence of diet composition was studied by feeding similar groups with diet of high fat content. The glucose incorporation in fatty acids was in all groups markedly and similarly inhibited by the high fat diet. The increase in lipoprotein lipase activity in heart and adipose tissue of control rats with high fat intake could not be demonstrated in any of the groups with ventromedial hypothalamic lesion. The plasma urea level in the control group was not affected by the diet, but tended to increase in the ventromedial hypothalamic lesioned groups on high fat intake. These findings demonstrate that the well known metabolic effects of ventromedial hypothalamic lesions are also manifest in obese insulin resistant male rats. Furthermore, the responses to changes in diet composition are different from those of the control rats.     

Metformin, but not exercise training, increases insulin responsiveness in skeletal muscle of Sprague-Dawley rats

We assessed the effects of combined metformin treatment and exercise training on body composition, on insulin concentration following glucose loading, on insulin-stimulated glucose transport in skeletal muscle, and on muscle glycogen content. Male Sprague-Dawley rats were treated for 35 days with or without metformin (320 mg/kg/day) and/or treadmill exercise training (20 min at 20 m/min, 5 days/wk). Because metformin reduces food intake, pair-fed controls were included. Metformin, training, and pair-feeding all decreased food intake, body weight, and insulin concentration following glucose loading. Metformin and training reduced intra-abdominal fat, but pair feeding did not. In isolated strips derived from soleus, epitrochlearis and extensor carpi ulnaris muscles, metformin increased insulin-stimulated transport of [3H]-2-deoxyglucose by 90%, 89% and 125%, respectively (P < 0.02) and training increased [3H]-2-deoxyglucose transport in the extensor carpi ulnaris muscle only (66%, P < 0.05). Pair-feeding did not alter [3H]-2-deoxyglucose transport. Training increased gastrocnemius muscle glycogen by 100% (P < 0.001). Metformin and pair-feeding did not alter muscle glycogen. We conclude that metformin reverses the maturation-induced impairment of insulin responsiveness in Sprague-Dawley rats by increasing insulin-stimulated glucose transport in skeletal muscle and that this effect is not secondary to reduced food intake. We also conclude that metformin and exercise training may increase insulin sensitivity by different mechanisms, with training causing increased glucose transport only in some muscles and also causing increased muscle glycogen storage.     

A steroidal glycoside from Polygonatum odoratum (Mill.) Druce. improves insulin resistance but does not alter insulin secretion in 90% pancreatectomized rats

The aim of this study was to investigate the effects of three steroidal glycosides (SG-100, SG-280, and SG-460) obtained from Polygonatum odoratum (Mill.) Druce. on insulin secretion, insulin action, and relative glucose uptake in various tissues of 90% pancreatectomized male Sprague-Dawley rats. One of the compounds (30 mg/kg body weight daily) with a 40%-fat diet was orally administered to a group of such rats for 13 weeks. On the day after a hyperglycemic clamp, euglycemic hyperinsulinemic clamp with 1 microCi of [1-(14)C]2-deoxyglucose per 100 g body weight was used. Serum glucose levels were lowest in the rats receiving SG-100. Insulin secretion from pancreatic beta-cells did not change with SG administration. Whole-body glucose disposal rates increased with SG-100 administration by 39%. SG-100 increased the glycogen contents and glycogen synthase activity in the soleus muscle of pancreatectomized rats. Uptake of [1-(14)C]2-deoxyglucose into the soleus muscle was higher in such rats receiving SG-100 than in rats receiving other compounds. In conclusion, SG-100 has an antihyperglycemic effect by promoting peripheral insulin sensitivity without changing insulin secretion.     

Maternal Deprivation Exacerbates the Response to a High Fat Diet in a Sexually Dimorphic Manner

Maternal deprivation (MD) during neonatal life has diverse long-term effects, including affectation of metabolism. Indeed, MD for 24 hours during the neonatal period reduces body weight throughout life when the animals are maintained on a normal diet. However, little information is available regarding how this early stress affects the response to increased metabolic challenges during postnatal life. We hypothesized that MD modifies the response to a high fat diet (HFD) and that this response differs between males and females. To address this question, both male and female Wistar rats were maternally deprived for 24 hours starting on the morning of postnatal day (PND) 9. Upon weaning on PND22 half of each group received a control diet (CD) and the other half HFD. MD rats of both sexes had significantly reduced accumulated food intake and weight gain compared to controls when raised on the CD. In contrast, when maintained on a HFD energy intake and weight gain did not differ between control and MD rats of either sex. However, high fat intake induced hyperleptinemia in MD rats as early as PND35, but not until PND85 in control males and control females did not become hyperleptinemic on the HFD even at PND102. High fat intake stimulated hypothalamic inflammatory markers in both male and female rats that had been exposed to MD, but not in controls. Reduced insulin sensitivity was observed only in MD males on the HFD. These results indicate that MD modifies the metabolic response to HFD intake, with this response being different between males and females. Thus, the development of obesity and secondary complications in response to high fat intake depends on numerous factors.     

Chronic Maternal Vitamin B12 Restriction Induced Changes in Body Composition & Glucose Metabolism in the Wistar Rat Offspring Are Partly Correctable by Rehabilitation

Maternal under-nutrition increases the risk of developing metabolic diseases. We studied the effects of chronic maternal dietary vitamin B12 restriction on lean body mass (LBM), fat free mass (FFM), muscle function, glucose tolerance and metabolism in Wistar rat offspring. Prevention/reversibility of changes by rehabilitating restricted mothers from conception or parturition and their offspring from weaning was assessed. Female weaning Wistar rats (n = 30) were fed ad libitum for 12 weeks, a control diet (n = 6) or the same with 40% restriction of vitamin B12 (B12R) (n = 24); after confirming deficiency, were mated with control males. Six each of pregnant B12R dams were rehabilitated from conception and parturition and their offspring weaned to control diet. While offspring of six B12R dams were weaned to control diet, those of the remaining six B12R dams continued on B12R diet. Biochemical parameters and body composition were determined in dams before mating and in male offspring at 3, 6, 9 and 12 months of their age. Dietary vitamin B12 restriction increased body weight but decreased LBM% and FFM% but not the percent of tissue associated fat (TAF%) in dams. Maternal B12R decreased LBM% and FFM% in the male offspring, but their TAF%, basal and insulin stimulated glucose uptake by diaphragm were unaltered. At 12 months age, B12R offspring had higher (than controls) fasting plasma glucose, insulin, HOMA-IR and impaired glucose tolerance. Their hepatic gluconeogenic enzyme activities were increased. B12R offspring had increased oxidative stress and decreased antioxidant status. Changes in body composition, glucose metabolism and stress were reversed by rehabilitating B12R dams from conception, whereas rehabilitation from parturition and weaning corrected them partially, highlighting the importance of vitamin B12 during pregnancy and lactation on growth, muscle development, glucose tolerance and metabolism in the offspring.     

The influence of long-term melatonin administration on basic physiological and metabolic variables of young Wistar:Han rats

The question of effects of long-term melatonin (MEL) administration have not yet been explained sufficiently, especially its metabolic consequences in young persons and animals. The aim of the present study was to analyze the effects of MEL given during prolonged time (for 3 months) and chronically (for 6 months) at the dose of 4 μg/mL of tap water, on the selected metabolic and hormonal parameters in young female and male Wistar:Han (WH) rats. The weights of selected organs, tissues, body weight gains and food and water intake were registered. Six weeks aged rats were adapted to standard housing conditions and light regimen L:D=12:12 h, fed standard laboratory diet and drank tap water (controls) or MEL solution ad libitum; finally they were sacrificed after overnight fasting. Prolonged MEL administration decreased serum glucose concentration and increased triacylglycerol and malondialdehyde concentration/content in the liver in females. In males MEL increased concentrations of serum phospholipids, corticosterone and liver malondialdehyde. MEL treatment reduced the body weight in both sexes and weight of epididymal fat in males, without any alterations of food and water intake. Chronic MEL administration reduced serum glucose concentration and increased concentration/content of glycogen, triacylglycerol and cholesterol in the liver and glycogen concentration/content in heart muscle in males. In females, the significant rise of serum corticosterone concentration and liver malondialdehyde content was recorded. MEL significantly increased liver weight and decreased thymus weight in males. MEL administration increased temporarily water intake in males, body and epididymal fat weights were similar to that in controls. Body weight of MEL drinking females was reduced in the 1^st half of experiment only; the food and water intake did not differ from control group. The response in WH rats on MEL was more prominent as in the Sprague-Dawley strain (our previous studies). Male rats were generally more affected, probably due to higher daily and total consumption of melatonin.     

Antecedent intake of traditional Asian-style diets exacerbates pancreatic beta-cell function, growth and survival after Western-style diet feeding in weaning male rats

The prevalence of type 2 diabetes has been rapidly increasing in conjunction with the westernization of diet patterns in Asia. We determined whether the antecedent consumption of traditional Asian-style diets (ADs) deteriorates insulin action, insulin secretion and pancreatic beta-cell mass after subsequent imposition of the diabetogenic challenge of Western-style diets (WDs) in weaning male Sprague-Dawley rats. Rats were provided AD (a low-fat and plant protein diet), WD (a high-fat and animal protein diet) or a control diet (CD) (a low-fat and animal protein diet) for 12 weeks. After 12 weeks, the groups were divided into two subsets; one set of the groups continued to consume their previous diets of WD, AD and CD for another 12 weeks, and the second set was divided into three groups represented by a switch in their designated diets from WD to AD, AD to WD and CD to WD. Whole-body glucose disposal rates and GLUT4 contents in soleus muscles were lower in WD regardless of the antecedent protein sources. The first-phase insulin secretion was higher in the CD group than in the other groups, whereas the second phase was lowered with AD consumption as antecedent and/or present diets. Asian-style diet and AD-WD intake did not compensate for insulin resistance due to the failure of beta-cell expansion via decreased proliferation. These findings suggest that the antecedent consumption of AD possibly accelerates and augments the development of glucose dysregulation via decreased insulin secretion capacity and pancreatic beta-cell mass when the diets switch to WD.     

Maternal treatment with oleoyl-estrone induces resistance to lipid accrual in their descendants

Objective: To determine whether treatment of rat dams with oleoyl‐estrone (OE) has an effect on the offspring's long‐term response to diet restriction during lactation. Methods and Procedures: Control, OE‐treated, and diet‐restricted dams were treated up to day 15 of lactation. Changes in food intake and body weight were recorded for dams and their pups. After weaning, pups received a 4‐week standard diet followed by a 4‐week period of high‐fat diet. Lipid, protein, and energy content of pups plus energy intake and efficiency. Serum metabolites (glucose, urea, and cholesterol) and serum hormones (adiponectin, leptin, insulin, and sexual hormones). Results: Neither pups from dams in the OE‐treated nor in the diet‐restricted group showed significant changes in weight, though these two groups ingested 79% of food ingested by controls. At weaning, the pups from OE‐treated rats were smaller than those of the control or diet‐restricted groups. These pups maintained the differences in size and lipid content during the 4‐week standard‐diet period, whereas pups from diet‐restricted dams showed a sharp decrease in their lipid content. During the 4 weeks of high‐fat diet, the male offspring from OE‐treated dams increased the difference in lipid content in relation to the pups from control dams whereas in females the differences decreased. Female offspring from diet‐restricted dams showed the most marked changes in metabolite and hormone levels in relation to controls. Discussion: Treatment of lactating dams with OE programs the metabolic response of their offspring to resist the challenge of a high‐fat diet that would lead to obesity in adulthood.     

Effects of a Fat Substitute,Sucrose Polyester,on Food Intake,Body Composition,and Serum Factors in Lean and Obese Zucker Rats

Sucrose polyester, a fat substitute, has shown promise in reducing blood cholesterol and body weight of obese individuals. Effects of this compound in the Zucker rat, a genetic model of obesity, are unknown. Thus, we examined food intake, body weight, body composition, and several metabolic parameters in sera of lean and obese female Zucker rats. Eight-week-old lean and obese animals were given a choice between a control diet (15% corn oil) and fat substitute diet (5% corn oil and 10% sucrose polyester) for 2 days. Next, one-half of the lean and obese groups received control diet; the remaining lean and obese rats received fat substitute diet for 18 days. Cumulative food intake was depressed in fat substitute groups relative to control-fed animals; however, this effect was more predominant in obese animals. Obese rats consuming fat substitute diet (O-FS) gained less weight as compared to obese control-fed animals (O-C). Lean rats given fat substitute (L-FS) did not have significantly different body weights as compared to the L-C group. Fat substitute groups, combined, had lower body fat and higher body water as compared to controls. The O-FS group had lower serum glucose and insulin and higher fatty acid levels compared to the O-C group. There were no differences in serum cholesterol, HDL, or triglyceride levels due to fat substitute diet. These data suggest that the obese Zucker rat is unable to defend its body weight when dietary fat is replaced with sucrose polyester.     

Effects of clenbuterol on insulin resistance in conscious obese Zucker rats

The present study was conducted to determine the effect of chronic administration of the long-acting beta(2)-adrenergic agonist clenbuterol on rats that are genetically prone to insulin resistance and impaired glucose tolerance. Obese Zucker rats (fa/fa) were given 1 mg/kg of clenbuterol by oral intubation daily for 5 wk. Controls received an equivalent volume of water according to the same schedule. At the end of the treatment, rats were catheterized for euglycemic-hyperinsulinemic (15 mU insulin. kg(-1). min(-1)) clamping. Clenbuterol did not change body weight compared with the control group but caused a redistribution of body weight: leg muscle weights increased, and abdominal fat weight decreased. The glucose infusion rate needed to maintain euglycemia and the rate of glucose disappearance were greater in the clenbuterol-treated rats. Furthermore, plasma insulin levels were decreased, and the rate of glucose uptake into hindlimb muscles and abdominal fat was increased in the clenbuterol-treated rats. This increased rate of glucose uptake was accompanied by a parallel increase in the rate of glycogen synthesis. The increase in muscle glucose uptake could not be ascribed to an increase in the glucose transport protein GLUT-4 in clenbuterol-treated rats. We conclude that chronic clenbuterol treatment reduces the insulin resistance of the obese Zucker rat by increasing insulin-stimulated muscle and adipose tissue glucose uptake. The improvements noted may be related to the repartitioning of body weight between tissues.     

Enhanced expression of lipogenic genes may contribute to hyperglycemia and alterations in plasma lipids in response to dietary iron deficiency

Iron deficiency (ID) remains a public health concern affecting ~25% of the world’s population. Metabolic consequences of ID include elevated plasma glucose concentrations consistent with increased reliance on glucose as a metabolic substrate, though the mechanisms controlling these responses remain unclear. To further characterize the metabolic response to ID, weanling male Sprague–Dawley rats were fed either a control (C; 40 mg Fe/kg diet) or iron-deficient (ID; 3 mg Fe/kg diet) diet or were pair-fed (PF) the C diet to the level of intake of the ID group for 21 days. In addition to reductions in hemoglobin, hematocrit, and plasma iron, the ID group also exhibited higher percent body fat and plasma triglycerides compared to the PF group. Steady-state levels of both plasma glucose and insulin increased 40 and 45%, respectively, in the ID group compared to the PF group. Plasma cortisol levels were decreased 67% in the ID group compared to the PF diet group. The systematic evaluation of the expression of genes involved in insulin signaling, glucose metabolism, and fatty acid metabolism in the liver and skeletal muscle revealed significant alterations in the expression of 48 and 52 genes in these tissues, respectively. A significant concurrent increase in lipogenic gene expression and decrease in gene expression related to β-oxidation in both the liver and skeletal muscle, in combination with differential tissue expression of genes involved in glucose metabolism, provides novel insight into the adaptive metabolic response in rodent models of severe iron deficiency anemia.     

Postnatal early overfeeding induces hypothalamic higher SOCS3 expression and lower STAT3 activity in adult rats

Postnatal early overnutrition (EO) is a risk factor for future obesity and metabolic disorders. Rats raised in small litters (SLs) develop overweight, hyperphagia, hyperleptinemia, hyperinsulinemia and hypertension when adults. As obesity is related to hyperleptinemia, leptin resistance and metabolic syndrome, we aimed to investigate body composition, plasma hormone levels, glucose tolerance and the leptin signaling pathway in hypothalamus from early overfed animals at weaning and adulthood. To induce postnatal EO, we reduced litter size to three pups/litter (SL), and the groups with normal litter size (10 pups/litter) were used as control. Rats had free access to standard diet and water postweaning. Body weight and food intake were monitored daily, and offspring were killed at 21 (weaning) and 180 days old (adulthood). Postnatal EO group had higher body weight and total and visceral fat mass at both periods. Lean mass and serum high-density lipoprotein cholesterol (HDL-C) were higher at 21 days and lower at 180 days. Small litter rats presented higher levels of globulins at both periods, while albumin levels were higher at weaning and lower at adulthood. There was higher leptin, insulin and glucose serum concentrations at 21 days old, while no glucose intolerance was observed in adulthood. Leptin signaling pathway was unaffected at weaning. However, postnatal EO induced lower JAK2 and p-STAT3, and higher SOCS3 expression in adult animals, indicating central leptin resistance in adulthood. In conclusion, postnatal EO induces obesity, higher total and visceral fat mass, lower HDL-C and central leptin resistance in adult life.     

急、慢性运动对2型糖尿病大鼠脂肪PI3K/AKT/GLUT4通路的影响

目的:探讨急性和慢性运动对2型糖尿病(T2DM)大鼠脂肪组织明磷脂酰肌醇3激酶(PI3K)/蛋白激酶B(AKT)/葡萄糖运载体4(GLUT4)信号通路的影响。方法:15月龄SD雄性大鼠52只随机分为正常对照组(n=13)和高脂组(n=39),分别喂养普通和高脂饲料。8周后,高脂组体重＞正常对照组20％,注射小剂量STZ后,血糖＞16.7 mmol/l,造模成功。将糖尿病模型组随机分为糖尿病对照组(DC,n=13),糖尿病慢性运动组(DCE,n=13),糖尿病急性运动组(DAE,n=13)。DCE组进行8周的游泳运动,DAE组进行一次性游泳运动。测定血脂,血糖和血清胰岛素,Western blot法测定脂肪PI3K、AKT和GLUT4蛋白含量。结果:糖尿病组体重、血脂、血糖、胰岛素显著高于正常对照组(P均＜0.01);高密度脂蛋白胆固醇(HDL-C)水平降低(P＜0.05),脂肪组织中PI3K、AKT和GLUT4蛋白表达下降(P均＜0.01)。糖尿病慢性运动组体重、血脂、血糖、胰岛素均出现显著性下降(P均＜0.01);HDL-C升高(P＜0.05),脂肪PI3K、AKT和GLUT4蛋白表达上升(P＜0.01)。糖尿病急性运动组血脂、血糖、胰岛素下降(P均＜0.05);HDL-C升高(P＜0.05),脂肪PI3K、AKT和GLUT4含量显著上升(P均＜0.05)。结论:①高脂饮食结合小剂量STZ诱导的T2DM大鼠脂肪组织PI3K/AKT通路受损,降低了胰岛素的敏感性。②急性、慢性有氧运动,均可以通过PI3K/AKT通路,改善糖脂代谢紊乱,慢性运动略优于急性运动。     

Intermittent fasting reduces body fat but exacerbates hepatic insulin resistance in young rats regardless of high protein and fat diets

Intermittent fasting (IMF) is a relatively new dietary approach to weight management, although the efficacy and adverse effects have not been full elucidated and the optimal diets for IMF are unknown. We tested the hypothesis that a one-meal-per-day intermittent fasting with high fat (HF) or protein (HP) diets can modify energy, lipid, and glucose metabolism in normal young male Sprague–Dawley rats with diet-induced obesity or overweight. Male rats aged 5 weeks received either HF (40% fat) or HP (26% protein) diets ad libitum (AL) or for 3 h at the beginning of the dark cycle (IMF) for 5 weeks. Epidydimal fat pads and fat deposits in the leg and abdomen were lower with HP and IMF. Energy expenditure at the beginning of the dark cycle, especially from fat oxidation, was higher with IMF than AL, possibly due to greater activity levels. Brown fat content was higher with IMF. Serum ghrelin levels were higher in HP-IMF than other groups, and accordingly, cumulative food intake was also higher in HP-IMF than HF-IMF. HF-IMF exhibited higher area under the curve (AUC) of serum glucose at the first part (0–40 min) during oral glucose tolerance test, whereas AUC of serum insulin levels in both parts were higher in IMF and HF. During intraperitoneal insulin tolerance test, serum glucose levels were higher with IMF than AL. Consistently, hepatic insulin signaling (GLUT2, pAkt) was attenuated and PEPCK expression was higher with IMF and HF than other groups, and HOMA-IR revealed significantly impaired attenuated insulin sensitivity in the IMF groups. However, surprisingly, hepatic and skeletal muscle glycogen storage was higher in IMF groups than AL. The higher glycogen storage in the IMF groups was associated with the lower expression of glycogen phosphorylase than the AL groups. In conclusion, IMF especially with HF increased insulin resistance, possibly by attenuating hepatic insulin signaling, and lowered glycogen phosphorylase expression despite decreased fat mass in young male rats. These results suggest that caution may be warranted when recommending intermittent fasting, especially one-meal-per-day fasting, for people with compromised glucose metabolism.