Zucker Fatty Rats Research Articles

Effects of insulin detemir on balloon catheter injured carotid artery in Zucker fatty rats

ObjectiveWe compared the effect of the long acting basal insulin analog detemir with neutral protamine Hagedorn (NPH) insulin, and normal saline on recovery from vascular injury (balloon catheter mediated) in an animal model of insulin resistance. MethodsFemale Zucker fatty rats were administered NPH/detemir/saline for 7days following which, they underwent balloon catheter mediated injury of left carotid artery, and were continued on the respective regimen for an additional 21days when they were sacrificed. We evaluated the injured carotid artery for intimal hyperplasia (Intima/Media ratio) and also, aortic arch protein for markers of oxidative stress and inflammation, in addition to expression and phosphorylation of eNOS using well established methods. ResultsThere was a significant difference in intimal hyperplasia (Intima/Media ratio) between control and detemir treated rats (1.3±0.09, 0.82±0.08; p<0.001) whereas the IM ratio in NPH treated rats was not significantly different from saline (1.17±0.1). Expression of p-eNOS (ser-1177) in both NPH and insulin detemir (1.3±0.15, 1.11±0.12) was significantly higher than controls (0.56±0.13; p<0.05). We did not find significant differences in the expression of MnSOD, eNOS and NFκB-p65. ConclusionWe conclude that in insulin resistant states, treatment with Insulin detemir but not NPH is associated with less intimal hyperplasia, although both insulins increased eNOS phosphorylation.

Pancreatic islet proteome profile in Zucker fatty rats chronically treated with a grape seed procyanidin extract

Grape seed procyanidin extract (GSPE) has been reported to modify glucose metabolism and β-cell functionality through its lipid-lowering effects in a diet-induced obesity model. The objective of the present study was to evaluate the effects of chronically administrated GSPE on the proteomic profile of pancreatic islets from Zucker fatty (ZF) rats. An isobaric tag for relative and absolute quantitation (iTRAQ) experiment was conducted and 31 proteins were found to be differentially expressed in ZF rats treated with GSPE compared to untreated ZF rats. Of these proteins, five subcategories of biological processes emerged: hexose metabolic processes, response to hormone stimulus, apoptosis and cell death, translation and protein folding, and macromolecular complex assembly. Gene expression analysis supported the role of the first three biological processes, concluding that GSPE limits insulin synthesis and secretion and modulates factors involved in apoptosis, but these molecular changes are not sufficient to counteract the genetic background of the Zucker model at a physiological level.

VO(dmpp)2 normalizes pre-diabetic parameters as assessed by in vivo magnetic resonance imaging and spectroscopy

Type 2 diabetes mellitus has been associated with obesity, metabolic syndrome, cardiovascular diseases and cancer. Attempts have been made for early diagnosis and finding effective drugs to prevent severe consequences and ameliorate the symptoms of this disorder. In this work, the pharmacological properties of VO(dmpp)2, [bis(1,2-dimethyl-3-hydroxy-4-pyridinonato)oxovanadium(IV)], were in vivo evaluated. For 4weeks fatty Zucker rats were subjected to a daily dose of VO(dmpp)2 (44μmol/kg) and their metabolic profile was followed by assessing different biological parameters at established time points: body weight, subcutaneous fat width and hepatic triglyceride content determined by magnetic resonance imaging and spectroscopy, respectively. A glucose tolerance test was performed at the end of the experiment. After treatment, treated obese rats presented a weight significantly lower than the non-treated obese animals (359.0±11.1 vs. 433.5±6.2g, P<0.05), a thinner subcutaneous fat width, and a statistically significant decrease in hepatic triglyceride content (5.41±0.59 vs. 21.03±1.40%, P<0.0005). Additionally, the glucose intolerant profile of fatty Zucker rats was completely reversed in treated animals (102.3±2.1 vs. 172.4±1.3mg/100mL; P<0.0005). These results reinforce the therapeutic action of VO(dmpp)2 which shows particular effects on lipid metabolism.

Sleeve Gastrectomy Improves Glucose Homeostasis in Zucker Diabetic Fatty Rats

Bariatric surgery improves glucose homeostasis, but the mechanism of action is poorly understood. The aim of this study was to assess the effect of sleeve gastrectomy (SG) on glucose homeostasis in two obese populations of rats. Two strains of rats [Zucker fatty (ZF) and Zucker diabetic fatty (ZDF)] were each divided into two groups: sham and SG. Food intake was measured daily, and weight was measured bi-weekly. Oral glucose tolerance testing (OGTT) was performed before and 45 days after surgery. In both strains of rats, there was no statistical difference in food intake and weight gain between the sham and SG rodents before and after surgery. In ZF rats, there was no change in fasting glucose or OGTT area under the curve (AUC) before or 45 days after surgery. In the ZDF rodents, the mean preoperative fasting glucose and OGTT AUC was 204 ± 25 and 25,441 ± 2,648, respectively. At 45 days after surgery, mean fasting glucose significantly increased in the sham (sham = 529 ± 26, p = 0.0003) but not in the SG rodents (SG = 289 ± 46, p = 0.1113). In ZDF sham animals, OGTT at 45 days showed a higher AUC compared to before surgery (44,983 ± 6,338, p = 0.006), whereas in ZDF SG rodents, the increase in AUC glucose approached but did not reach statistical significance (35,553 ± 3,925, p = 0.06). In ZF and ZDF rodents, SG did not influence food intake and weight evolution. In ZDF rodents, diabetes progressed in the sham group but not in the SG group.

Vitamin A status affects obesity development and hepatic expression of key genes for fuel metabolism in Zucker fatty rats

We hypothesized that vitamin A (VA) status may affect obesity development. Male Zucker lean (ZL) and fatty (ZF) rats after weaning were fed a synthetic VA deficient (VAD) or VA sufficient (VAS) diet for 8 weeks before their plasma parameters and hepatic genes' expression were analyzed. The body mass (BM) of ZL or ZF rats fed the VAD diet was lower than that of their corresponding controls fed the VAS diet at 5 or 2 weeks, respectively. The VAD ZL and ZF rats had less food intake than the VAS rats after 5 weeks. The VAD ZL and ZF rats had lower plasma glucose, triglyceride, insulin, and leptin levels, as well as lower liver glycogen content, net mass of epididymal fat, and liver/BM and epididymal fat/BM ratios (ZL only) than their respective VAS controls. VAD rats had lower hepatic Cyp26a1, Srebp-1c, Fas, Scd1, Me1, Gck, and Pklr (ZL and ZF); and higher Igfbp1 (ZL and ZF), Pck1(ZF only), and G6pc (ZF only) mRNA levels than their respective VAS controls. We conclude that ZL and ZF rats responded differently to dietary VA deficiency. VA status affected obesity development and altered the expression of hepatic genes for fuel metabolism in ZF rats. The mechanisms will help us to combat metabolic diseases.

Early induction of a brown-like phenotype by rosiglitazone in the epicardial adipose tissue of fatty Zucker rats

The epicardial adipose tissue (EAT) is "hypertrophied" in the obese. Thiazolidinediones are anti-diabetic, hypolipidemic drugs and are selective agonists for the gamma isoform of peroxisome proliferator-activated receptor (PPARγ). We evaluated the short-term effects of the prototype rosiglitazone (RSG, 5mgkg(-1)day(-1) for 4 days)on the expression of the genes and proteins (by real-time PCR and Western blot) involved in fatty acid (FA) metabolism in EAT of the obesefatty Zucker rat and compared the levels of expression with those in retroperitoneal adipose tissue (RAT). The glyceroneogenic flux leading to fatty acid re-esterification was assessed by the incorporation of 14C from [1-14C]-pyruvate into neutral lipids. RSG upregulated the mRNA for phosphoenolpyruvate carboxykinase, pyruvate dehydrogenase kinase 4, glycerol kinase, adipocyte lipid binding protein, adipose tissue triglyceride lipase and lipoprotein lipase in both RAT and EAT with a resulting increase in glyceroneogenesis that, however, was more pronounced in EAT than in RAT. Under RSG, fatty acid output was decreased in both tissues but unexpectedly less so in EAT than in RAT. RSG also induced the expression of thekey genes for fatty acid oxidation [carnitinepalmitoyl transferase-1, medium chain acyl dehydrogenase and very long chain acyl dehydrogenase (VLCAD)]in EAT and RAT with a resulting significant rise of the expression of VLCAD protein.In addition, the expression of the genes encoding proteins involved in mitochondrial processing and density PPARγ coactivator 1 alpha (PGC-1α), NADH dehydrogenase 1 and cytochrome oxidase (COX4) were increased by RSG treatment only in EAT, with a resulting significant up-regulation of PGC1-α and COX4 protein. This was accompanied by a rise in the expression of PR domain containing 16 and uncoupling protein 1, two brown adipose tissue-specific proteins. In conclusion, this study reveals that PPAR-γ agonist could induce a rapid browning of the EAT that probably contributes to the increase in lipid turnover.

Effects of vitamin A status on the responses of the hepatic genes’ expression to insulin and retinoic acid in primary hepatocytes from Zucker lean and fatty rats

Insulin‐mediated regulation of hepatic gene expression plays a key role in glucose and lipid homeostasis. This study was aimed to examine the hepatic gene expression in response to insulin and retinoic acid (RA) treatments in primary hepatocytes from Zucker rats of different vitamin A (VA) status. Primary hepatocytes were isolated from Zucker lean (ZL) or fatty (ZF) rats fed either vitamin A sufficient (VAS) or deficient diet (VAD) for 8 weeks after weaning. The mRNA levels of Gck, Pck1, Srebp‐1c and Pklr after insulin and RA stimulation for 6 hours were determined using real‐time PCR. In hepatocytes of ZL rats on either diet, insulin synergized with RA to induce the expression of Gck and Srebp‐1c. This was impaired in hepatocytes of ZF rats on VAS, but partially recovered in those on VAD diet. In lean hepatocytes, the Pck1 expression was suppressed by insulin and induced by RA respectively. The insulin‐suppressed Pck1 expression was impaired in hepatocytes from ZF rats fed VAS diet and partially restored in that fed VAD diet. The RA‐induced Pck1 expression was normal in hepatocytes from ZF rats fed VAS, and was enhanced in that fed VAD. The Pklr expression was similar between ZL and ZF and not affected by VA status. We conclude that VA status modulate the insulin‐ and RA‐regulated hepatic gene expression in hepatocytes of ZF rats. It suggests that micronutrients contribute to the hepatic insulin response.Grant Funding Source: AHA

Progression of Obesity‐Related Heart Dysfunction in Two Rat Models

The prevalence of obesity in the US has increased substantially over the past decades, with upwards of 33.8% of the population obese and 68% overweight. In childhood, 11.7% – 14.6% of preschoolers in developed countries and 16.4% of adolescents in the US are considered obese. Several animal models have been utilized to study the impact of obesity on the heart. In rats, the most prevalent models are the Zucker Fatty rats (ZF), a genetically modified rat with a leptin receptor deficiency, and normal Sprague Dawley rats (SD) fed a high fat diet. In the present study, we examined echocardiographic indices for each model in order to evaluate heart function. Values for IVRT/HR were significantly higher in ZF rats compared to Zucker Lean rats (0.058±0.010 ms/bpm vs, 0.045±0.009 ms/bpm, p&lt;0.05) at 19 weeks of age, however the values for SD rats were not significantly different after eating a high fat diet for 10 weeks. E/A ratio was not significantly different in ZF rats compared to lean controls, however was significantly decreased in SD rats fed a high fat diet compared to rats fed a normal diet (0.98 vs. 1.11; p&lt;0.05). Diastolic dysfunction was evident in both models, although the values for the ZF rats indicated less relative diastolic impairment than the SD rats fed a high fat diet. Continued work will examine the progression and mechanistic differences in these models, and their relevance to human obesity.

Effects of retinoid catabolism on the gene expression in primary rat hepatocytes and hepatoma cells

Vitamin A (retinol, ROL) is reversibly oxidized into retinal (RAL) by retinol dehydrogenases; retinal is irreversibly oxidized by retinal dehydrogenases into retinoic acid (RA) in cells. RA regulates gene expression via activation of retinoic acid receptor (RAR) and retinoid X receptor (RXR). We have shown that retinoids synergize with insulin to induce Srebp‐1c expression in primary rat hepatocytes. Therefore, we hypothesize that RA production controls the regulation of hepatic gene expression.The expression of Cyp26a1 (an RA responsive gene) was examined using real‐time PCR and used as a marker for RA production from ROL and RAL in primary hepatocytes and hepatoma cells. Here, we show that retinol and retinal dose‐dependently induced Cyp26a1 expression via activation of RAR and RXR in those cells. The expression levels of Rdh2, Rdh10, Raldh1, and Raldh3 (major retinoid catabolic enzymes) were examined in hepatocytes from Zucker lean (ZL) and fatty (ZF) rats. Only Rdh2 and Raldh1 were expressed at comparable level as that of 36B4 gene (the invariable control gene) in hepatocytes and hepatoma cells. In addition, the hepatocytes from ZF rats had higher expression level of Raldh1 than that from ZL rats.We conclude that hepatocytes actively metabolize retinol into RA, which directly regulate gene expression. The elevated Raldh1 expression in ZF hepatocytes may contribute to the altered lipid metabolism in ZF liver.Sponsor: Guoxun Chen, 1215 W. Cumberland Ave. 229 Jessie Harris Building, Knoxville, TN 37996Grant Funding Source : AHA

Whole apple but not apple pectin affects cardiac pathology and the oxidative stress/antioxidant transcriptome in obese rats

Apples provide both pectin fiber and phytochemicals that may confer cardiac benefits. However, their comparative effects on hypertension and cardiac function are unknown. In the obesity‐prone Zucker Fatty rat, we compared three diets: freeze‐dried whole apple powder (APP, 10% w:w), apple pectin (PEC), or control (CON). Diets were matched for macronutrients and calories, and animals were provided equivalent food per day. Body weight, fat mass and lean mass were not significantly different among groups. However, APP caused progressive reductions in serial systolic blood pressure, while PEC only caused transient and non‐significant reductions. After 120 days, APP but not PEC reduced cardiac hypertrophy, improved diastolic function, increased cardiac output, and reduced fibrosis. APP also reduced plasma oxidative stress marker malonyldialdehyde. APP but not PEC affected the cardiac transcriptome related to pro‐inflammatory NFκB activation and to antioxidant defense. Both APP and PEC reduced cardiometabolic risk factors like serum triglycerides, total cholesterol and fasting glucose but increased fecal cholesterol and bile acid content. Results suggest that diet‐altered lipid and glucose handling did not reduce cardiac pathology. In addition, reduced tissue oxidative stress by whole apple may be critical to cardiac‐specific effects; apple‐derived phytochemicals may mediate these benefits.

Differential Adipose Tissue Inflammatory State in Obese Nondiabetic Zucker Fatty Rats Compared to Obese Diabetic Zucker Diabetic Fatty Rats

Adipose tissue (AT) inflammation is linked to the pathogenesis of diabetes in obesity. Here, we compare the AT inflammatory state of 2 animal models of obesity and obesity plus diabetes, respectively. Obese nondiabetic ZF rats exhibited a trend towards increased proportions of CD11b positive cells in the adipose tissue stroma vascular fraction suggesting a state of increased AT inflammation compared to their lean littermates, but no alterations in systemic inflammatory parameters. In contrast, obese diabetic ZDF rats exhibited systemic as well as local AT inflammation with elevated levels of circulating Regulated upon Activation, Normal T-cell Expressed and Secreted Protein (Rantes), interleukin 1β (IL-1β) and monocyte chemotactic protein 1 (MCP-1), and an increased infiltration of adipose tissue CD11b positive cells. Our data provide a novel phenotypic characterisation of 2 common metabolic animal models and suggest an association of obesity with local inflammation in adipose tissue, and an association of diabetes with local inflammation in adipose tissue plus systemic inflammation. AT inflammation in obesity might therefore initiate a process that above a certain limits finally results in systemic inflammation and diabetes.

Triglyceride, nonesterified fatty acids, and prediabetic neuropathy: role for oxidative–nitrosative stress

Peripheral neuropathy develops in human subjects with prediabetes and metabolic syndrome before overt hyperglycemia. The contributions of impaired glucose tolerance and insulin signaling, hypertriglyceridemia and/or increased nonesterified fatty acids (NEFA), and hypercholesterolemia to this condition remain unknown. Niacin and its derivatives alleviate dyslipidemia with a minor effect on glucose homeostasis. This study evaluated the roles of impaired glucose tolerance versus dyslipidemia in prediabetic neuropathy using Zucker fatty (fa/fa) rats and the niacin derivative acipimox, as well as the interplay of hypertriglyceridemia, increased NEFA, and oxidative–nitrosative stress. Sixteen-week-old Zucker fatty rats with impaired glucose tolerance, obesity, hyperinsulinemia, hypertriglyceridemia, hypercholesterolemia, and increased NEFA displayed sensory nerve conduction velocity deficit, thermal and mechanical hypoalgesia, and tactile allodynia. Acipimox (100mgkg−1day−1, 4weeks) reduced serum insulin, NEFA, and triglyceride concentrations without affecting glucose tolerance and hypercholesterolemia. It alleviated sensory nerve conduction velocity deficit and changes in behavioral measures of sensory function and corrected oxidative–nitrosative stress, but not impaired insulin signaling, in peripheral nerve. Elevated NEFA increased total and mitochondrial superoxide production and NAD(P)H oxidase activity in cultured human Schwann cells. In conclusion, hypertriglyceridemia and/or increased NEFA concentrations cause prediabetic neuropathy through oxidative–nitrosative stress. Lipid-lowering agents and antioxidants may find a use in the management of this condition.

A Role for MRP8 in in stent restenosis in diabetes

ObjectiveThe most common cause of death in diabetes mellitus is cardiovascular disease. Patients frequently undergo vascular intervention such as stenting. The occurrence of in stent restenosis (ISR) has been reduced by the use of drug eluting stents in non-diabetic patients but the incidence of restenosis and stent thrombosis remains higher in diabetic patients. We investigated the pathogenesis of in stent restenosis in an animal model of type 2 diabetes mellitus. Methods and resultsStents were placed in Zucker Fatty Rat (ZFR) and wild type rat carotid arteries, and tissues were harvested 14days post surgery for morphometric analysis. Unstented carotid arteries from both groups were harvested for microarray analysis. In vitro apoptosis, proliferation and migration assays were performed on Rat and Human Aortic Endothelial Cells (EC).ZFRs developed an exaggerated intimal response to stent placement compared to wild type controls 14days post stent placement. MRP8 and MRP14 were up-regulated in unstented ZFR carotid arteries in comparison to controls. Expression of MRP8/14 was also elevated in EC exposed to high glucose conditions. EC function was impaired by high glucose concentrations, and this effect could be mimicked by MRP8 over-expression. MRP8 knockdown by shRNA significantly restored EC function after exposure to high glucose concentrations. MRP8 expression in glucose exposed cells was also inhibited using pharmacological blockade of glucose-induced pathways. ConclusionsEC dysfunction caused by elevated glucose levels could be mimicked by MRP8/14 over-expression and reversed/prevented by MRP8 knockdown. Thus, MRP8/14 likely plays a role in exaggerated ISR in diabetes mellitus, and MRP8 inhibition may be useful in improving outcome after stent placement in diabetes mellitus.

Feed consumption and weight gaining behavior of zucker fatty fafa rats with single and in combination treatment of clonidine and metformin

Background: Diabetes is metabolic disorder with high blood glucose level. Type-2 diabetes is associated with obesity, insulin resistance, and chronic hyperglycemia. So agents that are efficiently reduces weight gain along with diabetic control may play beneficial role in obese diabetic subjects. Methods: Zucker Fatty Rats were used for the study. Animals were divided in four groups, (control group, Clonidine group, metformin group and combination group). Normal weight gain and feed consumption data were obtained up to 9 weeks of age there after animals were started treatment according to above mentioned groups. During treatment again feed consumption and weight gain data were generated. The experimental results are expressed as the Mean ± SEM in each group. Statistical analysis has been performed by one way analysis of variance (ANOVA). Results: The data suggest that there is decrease in body weight gain during the treatment with clonidine and in combination of clonidine and metformin. If we consider weight gain of control as 100 % weekly than clonidine group shows 10.45 % weight gain while metformin shows 96.5 % weight gain and in combination group it shows 33.63 % weight gain. So, there is significant reduction in weight gain of the group treated with clonidine and combination of clonidine and metformin. Same time there is reduction in feed consumption of animals. Conclusions: The centrally acting drug Clonidine affects the feed consuming behavior and weight gain of animals. It shows hypophagic effect and reduces weight gain in single as well as in combination with metformin.

Formula Diet is Effective for the Reduction and Differentiation of Visceral Adipose Tissue in Zucker Fatty Rats

Formula diet (FD), which is used as a tool for calorie restriction, has beneficial effects on metabolic disorders in obese patients; however, the molecular mechanism is not fully understood. Sixteen-week-old male Zucker Diabetic Fatty (ZDF) rats were divided into 3 groups (n= 10 each): calorie-controlled low-fat diet [Control; 75 kcal/day, protein : fat : carbohydrate (P:F:C)=25:15: 60], calorie-restricted low-fat diet (CR-LFD; 56 kcal/day, P:F:C=25:15:60), and calorie-restricted FD (CR-FD; 56 kcal/day, P:F:C=50:14:36) group, and fed each diet for 4 weeks. Before the study, baseline data were obtained in 10 rats. After 4 weeks, body weight and epididymal fat weight were measured, and blood samples, mesenteric and subcutaneous adipose tissues were collected for analyses. Messenger RNA expression was evaluated by real-time PCR, and protein expression by Western blotting. The decrease in epididymal fat weight was significantly greater in the CR-FD group than in control and CR-LFD groups, although changes in body weight were not different among groups. The decrease in fasting plasma glucose and increase in plasma adiponectin were greater in the CR-FD group than in the control group, but not in the CR-LFD group. The decrease in triglyceride and increase in HDL-cholesterol were greatest in the CR-FD group. Both mRNA and protein of peroxisome proliferator-activated receptor γ coactivator (PGC)-1α, adiponectin, lipoprotein lipase and PPARγ were overexpressed in the CR-FD group, especially in mesenteric adipose tissue. FD may have beneficial effects on abdominal obesity and metabolic disorders by reducing visceral fat and improving glucose and lipid profiles, possibly through modulating adipose tissue function.

Diabetic Peripheral Neuropathy in Spontaneously Diabetic Torii-&lt;i&gt;Lepr&lt;/i&gt;&lt;sup&gt;&lt;i&gt;fa&lt;/i&gt;&lt;/sup&gt; (SDT Fatty) Rats

Spontaneously Diabetic Torii (SDT) rat is a hereditary model of diabetes. Although the SDT rat shows severe diabetic complications, the onset of hyperglycemia is late. SDT fatty rat, established by introducing the fa allele of the Zucker fatty rat to SDT rat, develops diabetes much faster than SDT rat. In the present study, diabetic peripheral neuropathy (DPN) was evaluated to show the further usefulness of this animal model. Motor nerve conduction velocity (MNCV) was delayed, and the number of sural nerve fibers was decreased in SDT fatty rat. Treatment of pioglitazone lowered blood glucose level and prevented delay of MNCV in SDT fatty rats. SDT fatty rat is a useful animal model for studies of DPN in type 2 diabetes.

Female heterozygous (+/fa) Zucker rats as a novel leptin-related mammary carcinogenesis model

The homozygous mutant fatty Zucker rat (fa/fa) is the prominent model for the research of obesity, one of the most well-known risk factor of postmenopausal mammary cancer. But the usage as a mammary gland carcinogenesis model is considered to be restricted due to the hypoplasia of mammary gland. In the present study, to find the validity of heterozygous mutant (+/fa) lean Zucker rats as a new leptin-related mammary carcinogenesis model, we examined whether the number of terminal end buds of mammary gland, the serum biochemistry, leptin concentration in serum and adipose tissue are changed in 7-week-old female +/+, +/fa and fa/fa rats, and whether these changes and leptin, TNF-α and VEGF mRNA expression in adipose tissue of +/+ and +/fa rats are influenced by 10% corn oil diet for 5 weeks. We confirmed that mild hyperleptinemia was more pronounced in 7-week-old +/fa as compared with wild type (+/+) and hypoplasia of mammary glands characterized by fewer numbers of terminal end buds in fa/fa was not observed in +/fa. With 10% corn oil diet, leptin mRNA expression in adipose tissue showed increasing tendency both in +/fa and +/+. Comparing with +/+, adipose tissue in +/fa treated with 10% corn oil diet was found to be significantly increased in the concentration of leptin protein and tended to be elevated expression of TNF-α mRNA. These results suggest that +/fa with 10% corn oil diet may be a useful model for investigation of the participation of leptin and TNF-α in mammary gland carcinogenesis.

High‐amylose rice improves indices of animal health in normal and diabetic rats

A high-amylose rice with 64.8% amylose content (AC) was developed by transgenic inhibition of two isoforms of starch branching enzyme (SBE), SBEI and SBEIIb, in an indica rice cultivar. The expression of SBEI and SBEIIb was completely inhibited in the transgenic line, whereas the expression of granule-bound starch synthase was normal. Compared with wild-type rice, drastic reductions in both SBEs in the transgenic rice increased apparent AC in flour from 27.2% to 64.8%, resistant starch (RS) content from 0% to 14.6% and total dietary fibre (TDF) from 6.8% to 15.2%. Elevated AC increased the proportion of long unit chains in amylopectin and increased onset gelatinization temperature and resistance to alkaline digestion; however, kernel weight was decreased. A rat feeding trial indicated that consumption of high-amylose rice decreased body weight gain significantly (P < 0.01); increased faecal mass, faecal moisture and short-chain fatty acids; and lowered the faecal pH. An acute oral rice tolerance test revealed that the high-amylose rice had a positive effect on lowering the blood glucose response in diabetic Zucker fatty rats. This novel rice with its high AC, RS and TDF offers potential benefits for its use in foods and in industrial applications.

Interleukin-10 expression induced by adeno-associated virus vector suppresses proteinuria in Zucker obese rats

Varying degrees of metabolic abnormalities mediated by chronic inflammation are implicated in the chronic glomerular injuries associated with obesity. Interleukin (IL)-10, a pleiotropic cytokine, exerts anti-inflammatory effects in numerous biological settings. In the present study, we explored the biological benefits of adeno-associated virus (AAV) vector-mediated sustained IL-10 expression against the pathological renal characteristics observed in Zucker fatty rats (ZFRs). We injected an AAV vector, encoding rat IL-10 or enhanced green fluorescent protein (GFP) into male ZFRs at 5 weeks of age. Subsequently, the renal pathophysiological changes were analyzed. Persistent IL-10 expression significantly reduced the urinary protein excretion of ZFRs compared with GFP expression (47.1±11.6 mg per mg·creatinine versus 88.8±30.0 mg per mg·creatinine, P<0.01). The serum levels of IL-10 negatively correlated with the urinary protein in AAV-treated rats (r=-0.78, P<0.01). Renal hypertrophy, increased widths in the glomerular basement membrane, and the lack of uniformity and regularity of the foot process of the visceral glomerular epithelial cells of ZFRs were significantly blunted by IL-10 expression. IL-10 also abrogated the downregulation of glomerular nephrin observed in ZFRs treated with the GFP vector. Our findings provide insights into the potential benefit of the anti-inflammatory effects of IL-10 on the overall management of glomerulopathy induced by the metabolic disorders associated with obesity.

The insulin sensitizing effects of PPAR-γ agonist are associated to changes in adiponectin index and adiponectin receptors in Zucker fatty rats

The adiponectin high molecular weight isoform (HMW-adp) and its relation with the other adiponectin isoforms (adiponectin index, SA), have been identified as essential for the adiponectin insulin sensitizing effects. The objective of this study is to gain further insight on the effect of the insulin sensitizing agents, PPAR-γ agonists, on the distribution of the adiponectin isoforms and the adiponectin receptors, adipoR1 and adipoR2 in an animal model of obesity and insulin resistance.To achieve the objective, Zucker fatty rats were treated with pioglitazone, rosiglitazone or placebo for six weeks. At the end of the treatment, total adiponectin, adiponectin isoforms and adiponectin receptors expression were measured. In order to see the possible relation with insulin sensitivity parameters, HOMA-IR, muscle insulin-stimulated glucose transport, muscle GLUT4 and plasma free fatty acids were also measured.The two glitazones improved insulin sensitivity and both muscle insulin-stimulated glucose transport and GLUT4 total content. Total plasma adiponectin and visceral fat HMW-adp were increased only by pioglitazone. On the other hand, both glitazones changed the distribution of adiponectin isoforms in plasma, leading to an increase in the SA of 21% by pioglitazone and 31% by rosiglitazone. Muscle adipoR1 expression was increased by both glitazones whereas liver adipoR2 expression was increased by rosiglitazone and tended to increase in the pioglitazone group.The insulin sensitizing action of glitazones is mediated, at least in part, by their effect on muscle insulin-stimulated glucose transport and by their direct influence on the adiponectin index and the adiponectin receptors expression.