Feeding Sprague-Dawley Rats Research Articles

Investigation of the toxicity and safety concerns of transgenic maize seeds expressing immunogenic F and HN protein genes against Newcastle disease virus.

The presented study investigated the potential toxicity and safety concerns associated with transgenic maize seeds expressing immunogenic F and HN protein genes against Newcastle disease virus (NDV). The experiment involved feeding Sprague-Dawley rats with transgenic maize seeds formulated into standard diets at levels of 30% (w/w) for a duration of 90days. The rats were divided into three groups, with 10 rats per group. We assessed various parameters including overall appearance, feed consumption, body weight, organ weight, hematological parameters, serum chemistry, and histopathology. The results of these assessments were compared between the control group and the treatment groups. The study findings revealed that there were no significant differences between the control and treatment groups in terms of overall appearance, feed consumption, body weight, organ weight, hematological parameters, serum chemistry, microscopic histopathology, and gross appearance of tissues. These observations suggest that the consumption of transgenic maize seeds did not lead to any treatment-related adverse effects or toxicological issues. Furthermore, the transgenic maize seeds were found to be nutritionally equivalent to their non-transgenic counterpart. Overall, no physiological, pathological, or molecular toxicity was observed in the Rats fed with transgenic feed.However, it is important to note that this study focused specifically on the parameters measured and the outcomes observed in Sprague-Dawley rats, and further research and studies are necessary to fully evaluate the safety and potential applications of transgenic edible vaccines in humans or other animals.

The Impact of Exposure Profile on the Efficacy of Dual Amylin and Calcitonin Receptor Agonist Therapy.

Background: Dual Amylin and Calcitonin Receptor Agonists (DACRAs) are treatment candidates for obesity and type 2 diabetes. Recently, a once-weekly DACRA (KBP-A) showed promise, potentially due to its different exposure profile compared to daily DACRA (KBP). Parathyroid hormone, a G-protein-coupled receptor (GPCR) class B agonist, is an example of the exposure profile being critical to the effect. Since KBP and KBP-A also activate GPCR class B, we compared the effects of injection to continuous infusion of short-acting KBP and long-acting KBP-A in obese and diabetic rats to shed light on the role of exposure profiles. Methods: To explore the metabolic benefits of dose optimization, the following dosing profiles were compared in High Fat Diet (HFD)-fed Sprague–Dawley rats and diabetic Zucker Diabetic Fatty (ZDF) rats: (1) KBP dosed once-daily by injection or by continuous infusion in HFD and ZDF rats; (2) KBP injected once-daily and KBP-A injected once every 3rd day (Q3D) in HFD rats; (3) KBP-A injected Q3D or by infusion in ZDF rats. Results: KBP and KBP-A, delivered by either injection or infusion, resulted in similar weight and food intake reductions in HFD rats. In ZDF rats, injection of KBP improved glucose control significantly compared to infusion, while delivery of KBP-A by injection and continuous infusion was comparable in terms of glucose control. Conclusion: different dosing profiles of KBP and KBP-A had no impact on metabolic benefits in HFD rats. In diabetic ZDF rats, KBP by injection instead of infusion was superior, while for KBP-A the effects were similar.

Abstract P227: A High Fat Diet Does Not Enhance Blood Pressure Dependence On Chemerin In Normotensive Rats

Various humoral factors produced by adipose tissue are suggested to contribute to obesity associated hypertension and cardiovascular pathology. The adipokine chemerin is a frontrunner candidate. Male Dahl SS rats fed a high fat (HF; 60% kCal) diet from weaning develop severe hypertension that is profoundly reduced by weekly treatment with an antisense oligonucleotide (ASO) that disables chemerin mRNA. Here we hypothesized that feeding a HF diet from weaning to male Sprague Dawley (SD) rats would similarly increase the dependence of blood pressure (BP) regulation on chemerin. Over 17 weeks of feeding, HF fed SD rats gained significantly more weight and body fat than those fed control (10% kCal) diet. Radiotelemeters were implanted at 17 weeks of age to measure BP. Two weeks of basal BP was collected, and as we and others have shown previously, the HF diet did not increase BP in SD rats (control = 117±2.5 mm Hg; HF = 122±2.2 mm Hg). Vehicle or Gen 2.5 ASO chemerin (25 mg/kg, sc) were then given once a week for four weeks. Gen 2.5 ASO chemerin caused a slowly developing but significant reduction in BP in control rats (-14.0±2.7 mm Hg) that was not significantly different from the BP fall in HF rats (-12.4±2.3 mm Hg). RT-PCR analyses validated complete loss of chemerin mRNA in the liver and fat (primary producers of chemerin) from rats given the Gen 2.5 ASO chemerin vs control. These data show that in normal, normotensive rats a HF diet alone is insufficient to increase BP dependence on chemerin

Decaffeinated light-roasted green coffee and green tea extract combination improved metabolic parameters and modulated inflammatory genes in metabolic syndrome rats

Background: Individually, green tea and green coffee have been extensively studied for mitigation of metabolic syndrome (MS) in both rats and humans; however, their combined effect requires further investigation. Thus, we compared the metabolic effect of combining green tea and decaffeinated light roasted green coffee on MS in rats. Methods: An MS animal model was constructed by feeding Sprague-Dawley rats with a high-fat-high-sucrose (HFHS) diet for eight weeks and a low dose of streptozotocin (STZ) injection at week 2. Rats fed with HFHS diets and injected with STZ successfully developed MS phenotypes, indicated by higher body weight, systolic blood pressure, plasma triglyceride level, plasma fasting blood glucose level, and lower plasma HDL-C level, compared to those fed with a normal chow diet. Subsequently, MS rats were continuously fed with HFHS and divided into four groups: MS rats, MS with 300 mg/bw.t green tea extract (GT), MS with 200 mg/bw.t green coffee extract (GC), and MS with combined green tea and green coffee extract (CM) for nine weeks. Results: Combining green tea and green coffee have synergistic effects on reducing plasma fasting blood glucose and triglyceride level. Inflammatory markers both in plasma and liver tissue robustly decreased in CM group rats. However, the reduction of systolic blood pressure was observed only in GT and CM groups. Moreover, all treatment resulted in an increase in plasma HDL-C level in MS rats. Conclusions: Our data highlighted that, in MS animal models, combined green tea and decaffeinated light roasted green coffee augment their several individual beneficial effects of improved metabolic parameters and modulated inflammatory genes.

Involvement of Circulating Exosomal MicroRNAs in Jian-Pi-Yi-Shen Formula Protection Against Adenine-Induced Chronic Kidney Disease

Jian-Pi-Yi-Shen formula (JPYSF) is a traditional Chinese medicine (TCM) formula used in clinic to treat chronic kidney disease (CKD) for decades. However, the mechanisms of JPYSF in treating CKD have not been fully elucidated. The aim of the present study was to test the renoprotective effect of JPYSF on CKD rat model and investigate the potential mechanism from the perspective of serum exosomal microRNAs (miRNAs). CKD rat model was induced by feeding Sprague-Dawley rats a diet containing 0.75% w/w adenine for four weeks. The rats in the treatment group were given 10.89 g/kg JPYSF by gavage every day, starting from the 3rd week of the adenine-containing diet for six weeks. Serum biochemistry and histopathology were used to evaluate the renoprotective effects of JPYSF. Serum exosomes were isolated by ExoQuick-TC PLUS exosomes extraction kit and were identified by transmission electron microscopy, nanoparticle tracking analysis, and western blot. Exosomal miRNAs profiling was analyzed by small RNA sequencing. The results showed that JPYSF treatment significantly lowered serum creatinine and blood urea nitrogen levels and alleviated renal pathological injury in CKD rats. Furthermore, serum exosomes were successfully isolated and identified. Small RNA sequencing revealed that 4 exosomal miRNAs (miR-192-5p, miR-194-5p, miR-802-5p, and miR-143-3p) were significantly downregulated in the CKD group and were markedly upregulated after JPYSF treatment. At last, miR-192-5p was identified as the most relevant miRNA for CKD diagnosis and JPYSF treatment. In conclusion, JPYSF protects kidney from adenine-induced CKD, which may be associated with modulation of exosomal miRNAs.

Effects of Huatan Jiangzhuo decoction on diet-induced hyperlipidemia and gene expressions in rats.

Huatan Jiangzhuo decoction (HJD) is a combination of six traditional Chinese medicines that were used for lipid metabolism-related disorders, but its efficacy and underlying mechanisms have not been explored by modern research strategies. This study aimed to investigate the therapeutic role of HJD in determining the transcriptome level. Hyperlipidemia model was established by feeding Sprague-Dawley rats with high-fat diet. Differentially expressed genes (DEGs) were detected by high-through transcriptome sequencing, followed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The total cholesterol (TC) and triglyceride (TG) levels in hyperlipidemia model rats were significantly increased, whereas high-density lipoprotein (HDL) concentration decreased when compared to normal rats, and HJD significantly downregulated TC concentrations and liver coefficient in the hyperlipidemia rats. Histology staining showed that HDJ greatly recovered the lipid accumulation in rat hepatic stellate cells and aortic arch vascular wall thickness of hyperlipidemia rats. One thousand nine hundred and thirty-six DEGs were identified in the HJD-treated hyperlipidemia rats, which were associated with various biological processes and signaling pathways such as peroxisome proliferator-activated receptors, AMP-activated Protein Kinase , and insulin signaling pathways. Quantitative reverse transcription-polymerase chain reaction further confirmed the downregulated expression of cholesterol 7-α-hydroxylase(CYP7A1), liver orphan receptor(LXRα),peroxisome proliferator-activated receptor gamma(PPARγ),andSterol Response Element-Binding Protein 1c(SREBP1c) genes in hyperlipidemia rats treated with HJD. Our data first elucidated the gene expression profile of high-fat diet-induced hyperlipidemia in rats after HJD treatment, and lipid metabolism-related genes (CYP7A1, LXRα, PPARγ, and SREBP1c) may be potentially biomarkers for HJD-alleviated hyperlipidemia.

Antiobesity effect of brewer’s yeast biomass in animal model

Abstract Brewer’s yeast biomass (BYB) is a byproduct of the beer-brewing process. This study explored the inhibition effect of BYB on obesity using an animal model. The prenylflavonoid and hop bitter acid contents of BYB were also evaluated to identify possible active substances. BYB ethanol extract contained four prenylflavonoids and six hop bitter acids. The content of hop bitter acids was higher than that of prenylflavonoids. Feeding Sprague–Dawley rats with 50 or 250 mg/kg BW doses of BYB ethanol extract and 250 mg/kg BW of BYB supernatant was found to significantly reduce tissue fat weight, serum triglyceride and hepatic triglyceride, serum insulin and HOMA-IR, as well as to increase liver antioxidant activity. Moreover, BYB ethanol extract could inhibit increased weight, feed efficiency, heparin-releasable lipoprotein lipase enzyme activity, and thiobarbituric acid reactive substance in liver. In particular, low doses of BYB ethanol extract could enhance lipolysis.

Alteration in iron efflux affects male sex hormone testosterone biosynthesis in a diet-induced obese rat model.

This study was motivated by clinical observations that dysmetabolic iron overload syndrome (DIOS) and an androgen deficiency are common features observed in obese adult men; however, the molecular mechanism underlying the effects of DIOS on androgen deficiency remains to be elucidated. We established a DIOS animal model by feeding Sprague-Dawley rats an iron/fat-enriched diet (50% fat plus 0.25, 1, or 2 g ferric iron per kg diet) for 12 weeks to induce iron dysfunction (indicated by decreased tissue iron efflux) in obese rats. Obese rats fed an iron/fat-enriched diet showed decreased levels of testicular total Testosterone (T) and iron exporter ferroportin but increased levels of testicular iron and hepcidin, and these effects were more evident with a >1 g ferric iron per kg diet. A western blot analysis showed that an iron/fat-enriched diet triggered testicular endoplasmic reticular (ER) stress but decreased mitochondrion biogenesis proteins (PGC1α and TFAM) and T-converting proteins (StAR, CYP11A, and 17β-HSD). TUNEL staining showed that >1 g ferric iron induced apoptosis mainly in germ cells and Leydig's cells. Uncontrolled testicular iron efflux may cause mitochondrial-ER dysfunction and affect T biosynthesis. Future study targeting the testicular hepcidin-ferroportin axis may offer a therapeutic tool to alleviate testicular iron retention and mitochondrial-ER stress in Leydig's cells.

In vivo study on the slow release of glucose in vacuum fried matrices

In vitro studies have shown that vacuum frying may be an effective process to reduce starch digestibility as it may limit gelatinization; this is significant as overconsumption of starchy foods contributes to obesity and type 2 diabetes. Although in vitro studies are an instrumental tool, in vivo studies allow observation of the overall effect on a living organism. The aim of this research was to assess how in vivo starch digestibility can be reduced when frying under vacuum (9.9 kPa), after feeding Sprague-Dawley rats, while also understanding its relationship to in vitro starch digestibility. Results showed that vacuum-fried dough has a lower degree of gelatinization (∼53.8%) and a maximal blood glucose level at 60 min (slower glycemic response) than atmospheric counterparts (∼98.3% degree of gelatinization and maximal blood glucose level at 30 min). Similarly, in vitro procedures exhibited less rapidly available glucose and higher unavailable glucose fractions in vacuum-fried dough.

Effect of a stilbene glycoside-rich extract from Polygoni Multiflori Radix on experimental non-alcoholic fatty liver disease based on principal component and orthogonal partial least squares discriminant analysis.

Polygoni Multiflori Radix is a traditional Chinese medicine used clinically to support the functions of the liver and kidneys and to treatment hyperlipidemia. In previous studies, an effective fraction, rich in 2,3,5,4′-tetrahydroxy stilbene-2-O-β-D-glucoside (TSG), was separated from Polygoni Multiflori Radix and demonstrated hypolipidemic activity. The present study aimed to systematically assess the effect of this fraction on non-alcoholic fatty liver disease (NAFLD). A NAFLD model was established by feeding Sprague-Dawley rats a high-fat diet with 10% fructose solution for 18 weeks. Hematoxylin and eosin staining was applied for hepatic histopathological analysis. In addition, enzyme activities, lipid metabolism, inflammatory factors and insulin resistance indices were measured using a fully automatic blood biochemistry analyser and ELISA. Furthermore, cytochrome P450 2E1 (CYP2E1) and peroxisome proliferator-activated receptor α (PPARα) mRNA and protein expression were evaluated using reverse transcription-quantitative polymerase chain reaction and western blot analysis. Principal component analysis and orthogonal partial least squares discriminant analysis were used to analyse the data. The results revealed that the TSG-rich fraction (TSGP) significantly lowered the serum total cholesterol and triglyceride levels, and the liver free fatty acid, CYP2E1 mRNA and malondialdehyde levels, in addition to mitigating hepatic enlargement and alleviating liver steatosis. Furthermore, it upregulated PPARα mRNA expression in the liver tissue. The results indicated that TSGP exhibited a protective effect against NAFLD and the underlying mechanism may involve augmentation of anti-lipid peroxidation capacity via regulation of PPARα and CYP2E1-mediated pathways.

Experimental chronic kidney disease attenuates ischemia-reperfusion injury in an ex vivo rat lung model.

Lung ischemia reperfusion injury (LIRI) is one of important complications following lung transplant and cardiopulmonary bypass. Although patients on hemodialysis are still excluded as lung transplant donors because of the possible effects of renal failure on the lungs, increased organ demand has led us to evaluate the influence of chronic kidney disease (CKD) on LIRI. A CKD model was induced by feeding Sprague-Dawley rats an adenine-rich (0.75%) diet for 2, 4 and 6 weeks, and an isolated rat lung in situ model was used to evaluate ischemia reperfusion (IR)-induced acute lung injury. The clinicopathological parameters of LIRI, including pulmonary edema, lipid peroxidation, histopathological changes, immunohistochemistry changes, chemokine CXCL1, inducible nitric oxide synthase (iNOS), proinflammatory and anti-inflammatory cytokines, heat shock protein expression, and nuclear factor-κB (NF-κB) activation were determined. Our results indicated that adenine-fed rats developed CKD as characterized by increased blood urea nitrogen and creatinine levels and the deposition of crystals in the renal tubules and interstitium. IR induced a significant increase in the pulmonary arterial pressure, lung edema, lung injury scores, the expression of CXCL1 mRNA, iNOS level, and protein concentration of the bronchial alveolar lavage fluid (BALF). The tumor necrosis factor-α levels in the BALF and perfusate; the interleukin-10 level in the perfusate; and the malondialdehyde levels in the lung tissue and perfusate were also significantly increased by LIRI. Counterintuitively, adenine-induced CKD significantly attenuated the severity of lung injury induced by IR. CKD rats exhibited increased heat shock protein 70 expression and decreased activation of NF-κB signaling. In conclusion, adenine-induced CKD attenuated LIRI by inhibiting the NF-κB pathway.

Evaluation of the Effects and Mechanism of L-Citrulline on Anti-obesity by Appetite Suppression in Obese/Diabetic KK-Ay Mice and High-Fat Diet Fed SD Rats.

L-Citrulline (L-Cit), a free amino acid from watermelon, has effects on hypertension and anti-oxidization; however, there are few reports of effects related to obesity. This study investigated the effects and mechanism of L-Cit on anti-obesity in obese/diabetic KK-Ay mice and high-fat diet fed Sprague-Dawley (SD) rats. L-Cit induced significant reduction of food intake, body weight and fat tissue mass in obese/diabetic KK-Ay mice. Moreover, blood glucose level did not change but free fatty acid level and serum insulin level were significantly decreased by treatment with L-Cit, suggesting that L-Cit improved glucose and fatty metabolism in obesity model mice. As well as obese/diabetic KK-Ay mice, there was a significant decrease in food intake and a tendency of body weight to decrease in high-fat diet fed SD rats treated with L-Cit. Also, levels of proopiomelanocortin (POMC), a food intake suppression peptide, increased in the hypothalamus. Our study suggests that L-Cit improves metabolic syndrome through decreased body weight by appetite suppression.

Abstract 046: High Fructose Intake Increases Phosphorylation and Trafficking of the Na/K/2Cl Cotransporter (NKCC22) In Rat Thick Ascending Limbs

A third of the US population consumes 20-40% of their caloric intake from added sugars with half of those calories from fructose. Fructose consumption is linked to salt-sensitive hypertension in humans and rodents. We found that feeding Sprague-Dawley rats 20% fructose in their drinking water did not increase blood pressure unless a high salt diet was added. The thick ascending limb (TAL) reabsorbs 25% of filtered NaCl, primarily via NKCC2. NKCC2 activity is increased by enhanced expression at the apical membrane and phosphorylation at Thr 96/101 . We found enhanced NKCC2 activity and trafficking in genetic models of salt-sensitive hypertension. However, the effect of fructose on NKCC2 regulation is unknown. Thus, we hypothesized that a fructose enriched diet stimulates NKCC2 activity. Sprague-Dawley rats were fed control diet or 20% fructose in drinking water for 1 week. TALs were isolated and phosphorylated and total NKCC2 was measured by surface biotinylation followed by western blot. A fructose-enriched diet increased surface-to-intracellular NKCC2 ratio by 60 ± 23% ( p< 0.05) and increased NKCC2 phosphorylation at Thr 96/101 by 8.02 ± 2.67 fold ( p <0.05). NKCC2 phosphorylation at the plasma membrane was also increased by 4.5 fold ( p <0.05). Total NKCC2 expression was reduced by 40.1 ± 8.9% ( p< 0.05). Since phosphorylation of NKCC2 at Thr 96/101 is mediated by STE20- and SPS1-related proline and alanine-rich kinases (SPAK) and oxidative stress-responsive kinase 1 (OSR1), we studied whether fructose stimulates expression and/or activity of SPAK/OSR1. Total SPAK/OSR1 expression was not enhanced by one week of a fructose diet. However, phosphorylation at Ser373 was enhanced by 2.8 ± 0.3 fold ( p< 0.05). We concluded that a fructose enriched diet increases phosphorylation and trafficking of NKCC2, enhancing its accumulation at the apical membrane. Moreover, a fructose diet increased SPAK/OSR1 kinases phosphorylation, suggesting they may be responsible for the enhanced NKCC2 phosphorylation. Our data suggest that a fructose-enriched diet promotes salt-sensitive hypertension in part by stimulating NKCC2 and TAL-dependent NaCl reabsorption.

Adiponectin receptor mediated weight regulation: an inflammation‐independent mechanism?

Adiponectin (ADP), a modulator of insulin actions, recently became an attractive therapeutic tool. We present here the effect of the first‐in‐class ADP receptor agonist (ADP355) on weight gain and biomarker patterns associated with long term high fat diet (HFD).Adult Sprague‐Dawley (SD) rats (n=23) were fed HFD (60% cal from fat) ad‐libitum for 15 weeks. ADP355 at 0.5mg/kg/dose, or saline was administered intraperitoneally every other day (n=3 each); weight gain, food intake, glucose (Glc) levels and blood biomarkers were assessed weekly. C‐reactive protein, glucagon, IL‐6, TNFα, amylin, insulin and leptin levels were measured by a multiplexed bead‐specific Luminex assay. The assays included 3 randomly selected matched controls. Results were assessed by student t‐test.After 15 weeks of treatment, the ADP355 group exhibited reduced weight gain (P<0.009), lower Glc levels (P=0.02), n=20, and significantly decreased glucagon (P<0.015) levels relative to control. While leptin levels increased, TNFα and amylin levels decreased significantly in the control group (P<0.002 for all). In the ADP355 group, leptin expression maintained a modestly increasing trend, however, no change was observed in the TNFα or amylin levels. In HFD fed SD rats, stimulation of the ADP receptor might be beneficial for weight gain prevention; however, our data do not support an anti‐inflammatory activity of ADP355 administration.

Perivascular fat impairs contraction in aorta from obese but not lean adult rats

Aortic perivascular fat limits the ability of the aorta to contract. We hypothesized that constriction would be further impaired in rats fed a high fat (HF) diet. Male Sprague Dawley (SD) rats were fed a HF diet from 3–20 weeks of age, control rats received normal chow (n=4–6 in each group). Aortae were removed and isometric force generation was measured in the presence and absence of fat. The HF rats weighed more than the controls (401±9 vs 465±10g, control vs HF p<0.05) and had more abdominal fat (5.6±0.3 vs 16.5±1.2g, control vs HF p<0.05). Surprisingly, the presence of fat in the control rats had no effect on the contraction mediated by phenylephrine (PE) or angiotensin II (Ang II). Fat did cause a marked impairment in the contraction in aorta from HF rats. Interestingly, the clean aorta from the HF rats also exhibited impaired PE and Ang II mediated contraction when compared to clean aorta from control rats. We have shown that fat impairs contraction in aorta from young control chow fed SD rats. The present study suggests that fats ability to limit contraction is reduced with age in control but not obese rats; the mechanisms responsible for this remain to be elucidated. Maximum contraction (mg increase from baseline) Contractile Agent Control Control + Fat HF HF+Fat PE 1580±210 1595±68 1280±76# 855±59* Ang II 545±90 533±73 367±80# 157±67* different from clean aorta from HF rats, different from clean aorta from control rats

Synthesis and evaluation of the hypoglycemic and hypolipidemic activity of novel 5-benzylidene-2,4-thiazolidinedione analogs in a type-2 diabetes model

This article reports synthesis and evaluation of two novel thiazolidinedione ring containing molecules namely (Z)-5-(2-(4-((2,4-dioxothiazolidin-5-ylidene)methyl)phenoxy)acetyl)-2-hydroxybenzamide (4) and (Z)-2-(4-((2,4-dioxothiazolidin-5-ylidene)methyl)phenoxy)-N-(5-nitrothiazol-2-yl)acetamide (7). The new chemical entities were tested for hypoglycemic activity and for their total cholesterol (CHL) and triglyceride (TG) lowering effect in high-fat diet (HFD) fed Sprague–Dawley rats. The synthesized molecules showed significant reduction in blood glucose, CHL, and TG levels after 14 days of treatment.

Effect of rice-bran water extract on the amelioration of pre-diabetic state in high-fat feeding rats

The water extract of rice bran (RBE) was shown to reduce fasting blood sugar and glycosylated hemoglobin in diabetes [1]. Being a staple food among Thai, the effect of RBE on pre-diabetic state was interested. The study was done in high-fat (65% of total calories) feeding Sprague-Dawley rats. Four groups of 8 rats each were separately either co-treated daily with three doses (22.05, 220.5, 2205mg/kg) of RBE or 9.55mg/kg metformin, twice daily. After four weeks of treatments, RBE at the highest dose was able to significantly (p<0.05) reduce the weight gain (125.98±7.32 gm vs 160.72±10.03 gm), visceral fat (8.99±0.72 gm vs 13.95±0.44 gm) and area under the glucose-clearance curve (1248.83±189.62 vs 2787.75±472.54). The percentage of homeostasis model assessment of B-cell function (HOMA-B) was reduced when rats were fed with high-fat diet but the value was increased when those rats were also received RBE, though there was no statistic significance. The value of the homeostasis model assessment of insulin resistance (HOMA-IR) was not affected by the treatment.

Osthole Improves Fat Milk-Induced Fatty Liver in Rats: Modulation of Hepatic PPAR-alpha/gamma-Mediated Lipogenic Gene Expression

The objectives of this study were to determine the therapeutic effect of osthole, an active constituent isolated from Cnidium monnieri (L.) Cusson (Apiaceae), in hyperlipidemic fatty liver (HFL) rats and investigate the possible mechanism of the osthole treatment. The HFL rat model was established by feeding Sprague-Dawley rats with fat milk for 6 weeks. The experimental rats were then treated with a dose of osthole of 5 - 20 mg/kg for 6 weeks. After the treatment, total cholesterol (TC) and triglycerides (TG) in serum and hepatic tissue, as well as the coefficient of hepatic weight were measured. The results showed that the TC and TG in both serum and hepatic tissue and the coefficient of hepatic weight in the osthole-treated rats were lower as compared to those in the experimental group, respectively (P < 0.05 or P < 0.01). Moreover, as compared to the control group, the osthole treatment increased the PPARalpha/gamma mRNA expression by 58.0 - 84.0 % and 20.4 - 77.4 %, respectively. The related target genes for mRNA expression were also increased by osthole-treatment, e. g., 53.4 - 93.2 % for CYP7A, 21.1 - 63.2 % for L-FABP and 34.1 - 57.3 % for FATP4, while the DGAT mRNA expression was decreased by 26.0 - 44.4 %. The therapeutic effect of osthole was further confirmed by histological evaluation of the liver showing a dramatically decreased lipid accumulation and improved ultrastructure of hepatocytes. In conclusion, osthole exerts therapeutic effects on fat milk-induced fatty liver in rats, by regulating mRNA expression of the target genes of CYP7A, DGAT, L-FABP and FATP4 via increasing the PPARalpha/gamma mRNA expression.

High gastrin cell activity and low ghrelin cell activity in high-anxiety Wistar Kyoto rats

Ghrelin is produced by gastric A-like cells and released in response to food deprivation. Interestingly, psychological stress also raises circulating ghrelin levels. This study compared plasma ghrelin levels in Sprague-Dawley (SPD) rats and high-anxiety Wistar Kyoto (WKY) rats. The two strains were also compared with respect to plasma gastrin, a gastric hormone with a pre- and postprandial release pattern opposite to that of ghrelin, and to the activity of the gastrin-dependent, histamine-forming ECL cells in the gastric mucosa. The rats were killed after being freely fed or after an over-night fast. The stomachs were weighed and tissue samples were collected for histological and biochemical analysis. Plasma ghrelin and gastrin levels were determined by RIA. While fasted SPD rats had higher plasma ghrelin levels than fasted WKY rats (P < 0.001), plasma ghrelin did not differ between freely fed rats of the two strains. Gastrin levels were higher in fed WKY rats than in fed SPD rats (P < 0.001). Despite the higher plasma gastrin level, the oxyntic mucosal histidine decarboxylase (HDC) activity (a marker of ECL-cell activity) in fed rats and the mucosal thickness did not differ between the two strains. In a subsequent study, rats were subjected to water-avoidance stress for 60 min, causing plasma gastrin to increase in WKY rats (P < 0.001) but not in SPD rats. In conclusion, high-anxiety WKY rats had lower circulating ghrelin and higher gastrin than SPD rats in both the fasted and fed state, while the ECL-cell activity (HDC activity) was only moderately affected.

Effect of suboptimal nutrition during lactation on milk protein gene expression in the rat

Human milk provides infants with proteins that aid in the prevention of infections and facilitate the digestion and absorption of other nutrients. Maternal diet is not believed to affect the protein concentration of breast milk. However, the maternal factors that regulate the expression of genes for specific milk proteins are not well characterized. We hypothesized that nutrition could be one of the factors. We fed Sprague–Dawley rats five diets representing common nutrient deficiencies and energy deficiency during pregnancy and lactation: low-zinc (Zn; 7 μg/g), low-iron (Fe; 6 μg/g), low-protein (12.5% albumin), pair-fed control diet (lactation only, 20% less kcal) and control diet (Zn, 25 μg/g; Fe, 100 μg/g; protein, 21%) ad libitum. At day 10 of lactation, the mammary gland was removed for RNA extraction. Northern blots of mRNA from the different groups were performed by hybridization with β-casein and whey acidic protein (WAP) cDNA probes. The expression of β-casein mRNA in rat mammary gland was significantly ( P<.005) increased in the pair-fed group when compared to the control group. The expression of WAP mRNA was also significantly ( P<.005) increased in the pair-fed group as well as in the low-Fe group when compared to the control group. The concentration of β-casein in milk was significantly higher for the low-zinc and the pair-fed groups only. The concentration of WAP in milk was not different among groups. These results suggest that compromised maternal nutrition can affect the expression of two individual milk proteins and may have functional implications with regard to bioactive proteins in milk.