Rat Model Of Metabolic Syndrome Research Articles

Regional functional and structural abnormalities within the aorta as a potential driver of vascular disease in metabolic syndrome.

What is the central question of this study? Is aortic dysfunction, a significant contributor to cardiovascular disease in metabolic syndrome, expressed uniformly across both the thoracic and abdominal aorta? What is the main finding and its importance? Our study shows that, in the setting of metabolic syndrome, functional and structural deficits in the aorta are differentially expressed along its length, with the abdominal portion displaying more extensive vascular abnormalities. It is, therefore, likely that early interventional strategies targeting the abdominal aorta might alleviate cardiovascular pathologies driven by the metabolic syndrome. The extent of vascular dysfunction associated with metabolic syndrome might vary along the length of the aorta. In this study, we investigated regional functional and structural changes in the thoracic and abdominal aorta of a rat model of metabolic syndrome, namely, high-fat diet (HFD) streptozotocin-induced diabetes mellitus (HFD-D). Four-week-old male Wistar albino rats were fed with either HFD or control diet (CD) for 10weeks. At week6, 40mg/kg streptozotocin and its vehicle were injected i.p. into HFD and CD groups, respectively. At the end of the feeding period, rats were euthanised and aortic segments collected for assessment of vascular functional responses and histomorphometry. Tail-cuff systolic blood pressures (154±6vs. 110±4mmHg) and areas under the curve for oral glucose and i.p. insulin tolerance tests were greater in HFD-D versus CD rats. Abdominal aortic vasoconstriction in response to noradrenaline and KCl was greater in HFD-D compared with CD rats. Thoracic vasoconstrictor responses to noradrenaline, but not KCl, were greater in the HFD-D group. Abdominal, but not thoracic, endothelium-dependent vasorelaxation in response to acetylcholine was blunted in HFD-D relative to CD rats; however, nitric oxide-dependent vasorelaxation in HFD-D rats was impaired in both thoracic and abdominal segments. The abdominal aorta of HFD-D rats showed deranged interlamellar spacing and increased lipid plaque deposition. In conclusion, vascular dysfunction in metabolic syndrome is expressed differentially along the length of the aorta, with the abdominal aorta exhibiting increased susceptibility to vasoconstrictors and greater deficits in endothelium-dependent relaxation. These vascular functional abnormalities could potentially underlie the development of hypertensive cardiovascular disease associated with the metabolic syndrome.

N-acetyl cysteine can blunt metabolic and cardiovascular effects via down-regulation of cardiotrophin-1 in rat model of fructose-induced metabolic syndrome

In this study, we investigated the ability of N-acetyl cysteine (NAC) to alleviate the metabolic disorders in fructose-induced metabolic syndrome (MS) in male rats and to examine its protective effect on aortic and cardiac tissues via its influence on cardiotrophin-1 (CT-1) expression. NAC (20 mg/kg b.w./day) was administered to fructose induced MS animals for 12 weeks. Chronic fructose consumption (20% w/v) increased body weight gain, relative heart weight, systolic blood pressure (SBP), diastolic blood pressure (DBP), insulin resistance (IR), and associated with metabolic alterations. Histological and immunohistochemical examination revealed aortic stiffness and myocardial degeneration and fibrosis together with increased CT-1 expression. Treatment with NAC improved IR, SBP, DBP, and mitigated dyslipidaemia and oxidative stress. Additionally, NAC down-regulated CT-1 expression in the heart and aorta. These findings demonstrated the protective effect of NAC against aortic and myocardial degeneration and fibrosis through down-regulation of CT-1 in fructose induced MS animal model.

Anti-apoptotic and pro-survival effects of longan flower extracts on rat hearts with fructose-induced metabolic syndrome.

The aim of this study was to investigate the effects of longan flower (LF) water extract on cardiac apoptotic and survival pathways in rat models of fructose-induced metabolic syndrome. The study findings revealed that the levels of glucose, insulin, triglyceride, and cholesterol and TUNEL-positive apoptotic cells were significantly increased in the HF group compared with the control group; whereas, the levels were decreased in the HFLF group. The expressions of Fas, FADD, and activated caspases 8 and 3, as well as the expressions of Bax, Bak, Bax/Bcl-2, Bak/Bcl-xL, cytosolic cytochrome c, and activated caspases 9 and 3 were increased in the HF group were significantly reversed in HFLF administrated group. Furthermore, LF extract increased IGF-1R, p-PI3K, p-Akt, Bcl-2, and Bcl-xL expression compared to HF group. Taken together, the present findings help identify LF as a potential cardioprotective agent that can be effectively used in treating fructose-induced metabolic syndrome.

Pathophysiological justification of age- and gender-dependent morphological changes in the adipose tissue in rat models of metabolic syndrome

Introduction: The mechanisms of metabolic syndrome (MS) is one of the urgent issues in medicine. Regional distribution of the adipose tissue should be diagnosed at clinical examination, as the morphometric parameters of the cells of the active adipose tissue components may indicate the metabolic state. Aim: The aim of the study was to evaluate the differences in morphological and histological parameters of the adipose tissue associated with the development of MS in animals of different ages and gender. Material and methods: An experimental study was carried out on 144 WAG/G Sto white rats, divided into three study groups. Group 1 included young immature rats, 3 months old; group 2 consisted of 48 sexually mature rats, aged 5–6 months; group 3 consisted of 48 old rats, 18 months old. Each group was divided into 2 subgroups, control and experimental, and was additionally divided according to gender. Results and discussion: The body mass indices and specific weights of mesenteric, epididymal, retroperitoneal and subcutaneous adipose tissue were determined in rats, as well as morphological characteristics of adipocytes of the adipose tissue. It was shown that histological and morphological changes in the adipose tissue of the animals were age- and gender-dependent, and that obesity is associated with chronic inflammation of the adipose tissue. Conclusions: The results of the study can be used for further determination of possible age and gender differences in the adipose tissue involvement in the development of chronic inflammation, as well as monitoring and correction of adipose tissue dysfunction in MS.

Ileal interposition improves metabolic syndrome parameters in a rat model of metabolic syndrome induced by monosodium glutamate

AimsMetabolic syndrome (MetS) is a cluster of metabolic abnormalities. Anatomically restructuring of the gastrointestinal system has recently been an important subject of research in the treatment of MetS and closely related diseases. The aim of this study is to ensure the remission of parameters that define MetS by ileal interposition (IT) and to examine the effect of IT on plasma total GLP-1 and pancreatic GLP-1R expression. Main methodsTo induce MetS, newborn male Wistar albino rats were given MSG (4 g/mg) on days 0, 2, 4, 6, 8, and 10. The control group was injected with saline. In the 5th month, IT or sham surgery was performed on the MetS rats. The lipid levels, abdominal obesity, insulin level, OGTT, Lee index, HOMA-IR, plasma GLP-1 and pancreas GLP-1R expression were evaluated 2 months after surgery. Key findingsThe results showed that IT significantly improved hyperinsulinemia (p = 0.013) and lipid profile (TG p = 0.0001; TCHOL p = 0.018; HDL p = 0.001). Furthermore, it normalized the Lee index (p = 0.006) and insulin resistance. The IT did not affect the secretion of the GLP-1, but the expression levels of pancreas GLP-1R were increased (p = 0.006). SignificanceIT surgery corrected the MetS parameters in this rat model. The healing effects of IT surgery could be caused by mechanisms in the target tissues of insulin. The decrease in pancreatic GLP-1R levels in the MetS groups might be a compensatory response to the harmful effects of hyperinsulinemia in these groups. These results show that IT can be useful in the treatment of MetS.

FABP4 inhibitor attenuates inflammation and endoplasmic reticulum stress of islet in leptin receptor knockout rats.

Metabolic syndrome is characterized by abdominal obesity, hypertriglyceridemia and hyperglycemia. Fatty acid binding protein 4 (FABP4), as a member of intracellular lipid chaperones, is not only engaged in lipid transport but involved in inflammation and insulin resistance. The present study was to investigate the effects of BMS309403, a specific FABP4 inhibitor, on metabolic syndrome and its possible molecular mechanisms in islets. Leptin receptor knockout (Lepr-/-) rat, a novel and representative animal model of metabolic syndrome, was adopted in this study. Lepr-/- male rats and their wild littermates were grouped and intragastrically administered with BMS309403. Glucose Tolerance Test (GTT) and Insulin Tolerance Test (ITT) were performed on all rats. Serum insulin was detected by ELISA. The metabolic characters, as well as liver and kidney functions, were evaluated by serum biochemical assay. Immunohistochemistry and Western blot were adopted to detect the expression levels of FABP4, CD68, GRP78, ATF6, p-IRE1a, and Cleaved caspase-3. Lepr-/- rats showed prominent characteristics of metabolic syndrome with increased FABP4, inflammatory infiltration, ER stress and apoptosis in islets. BMS309403 administration attenuated inflammation, ER stress and apoptosis in Lepr-/- rat islets while stimulating insulin secretion as well as improving manifestation of metabolic syndrome without hepatic and renal toxicity. FABP4 increased in Lepr-/- rat islets and might be involved in the regulation of islet inflammation and apoptosis via ER stress. FABP4 inhibitor BMS309403 could ameliorate islet inflammation and apoptosis in metabolic syndrome through suppressing ER stress.

SIRT1 alleviates hepatic ischemia-reperfusion injury via the miR-182-mediated XBP1/NLRP3 pathway

The hepatoprotection of histone deacetylase sirtuin 1 (SIRT1) has been identified to attenuate ischemia-reperfusion (IR)-triggered inflammation and liver damage. This study was performed to characterize the function of SIRT1 in hepatic IR injury. In in vivo assays on liver-specific knockout mice of SIRT1, we first validated the effect of SIRT1 knockout on liver damage and XBP1/NLRP3 inflammasome activation. Next, we examined whether knockdown of XBP1/NLRP3 or miR-182 agomir could reverse the effect of SIRT1 knockout. In in vitro assays, NCTC1469 cells subjected to hypoxia/reoxygenation (H/R) were transduced with small interfering RNA (siRNA)/activator of SIRT1 or miR-182 agomir to confirm the effect of SIRT1 on NCTC1469 cell behaviors as well as the regulation of miR-182 and the XBP1/NLRP3 signaling pathway. Hepatic IR injury was appreciably aggravated in SIRT1 knockout mice, and SIRT1 knockdown abolished the inhibition of XBP1/NLRP3 inflammasome activation, which was reversed by NLRP3 knockdown, XBP1 knockdown, or miR-182 agomir. Mechanistically, miR-182 expression was positively regulated by SIRT1 in hepatic IR injury in mice, and miR-182 inhibited the expression of XBP1 by binding to the 3′ untranslated region (UTR) of XBP1. The histone deacetylase SIRT1 inhibits the downstream XBP1/NLRP3 inflammatory pathway by activating miR-182, thus alleviating hepatic IR injury in mice.

The prebiotic fiber inulin ameliorates cardiac, adipose tissue, and hepatic pathology, but exacerbates hypertriglyceridemia in rats with metabolic syndrome.

Prebiotics ameliorate dysbiosis and influence metabolism and the immune system, but their effects on cardiovascular complications in metabolic disorders remain largely unknown. We here investigated the effects of the soluble fiber inulin on cardiac, adipose tissue, and hepatic pathology as well as on metabolic disorders in DahlS.Z-Leprfa/Leprfa (DS/obese) rats, an animal model of metabolic syndrome (MetS). DS/obese rats and their homozygous lean (DahlS.Z-Lepr+/Lepr+, or DS/lean) littermate controls were fed a purified diet containing 5% or 20% inulin from 9 to 13 wk of age. The high-fiber diet ameliorated hypertension, left ventricular inflammation, fibrosis and diastolic dysfunction; attenuated adipose tissue inflammation and fibrosis; and alleviated the elevation of interleukin-6 levels, without affecting insulin resistance, in DS/obese rats. In addition, high fiber intake ameliorated lipid accumulation, inflammation, and fibrosis; attenuated the reduction in AMPK activity; upregulated sterol regulatory element-binding protein-1c gene expression; and increased the expression of microsomal triglyceride transfer protein gene in the liver of DS/obese rats. It also mitigated increases in total and non-high-density lipoprotein cholesterol levels but increased the triglyceride concentration in serum in these rats. None of these parameters were affected by high dietary fiber in DS/lean rats. The proportion of regulatory T cells in adipose tissue was influenced by dietary fiber but not by genotype. Our results indicate that inulin exacerbates hypertriglyceridemia but alleviates hypertension and cardiac injury as well as adipose tissue and hepatic pathology in MetS rats.NEW & NOTEWORTHY Prebiotics ameliorate dysbiosis and influence metabolism and the immune system, but their effects on cardiovascular complications in metabolic disorders remain largely unknown. Inulin ameliorated hypertension, cardiac injury, and diastolic dysfunction without affecting obesity or insulin resistance in a rat model of metabolic syndrome. The favorable cardiac effects of inulin may be related to inhibition of systemic inflammation associated with a reduction in circulating interleukin-6 levels. Additionally, inulin exacerbated hypertriglyceridemia but alleviates adipose tissue and hepatic pathology in these animals, as well as increased the number of regulatory T cells in adipose tissue.

Effects of the CB1 Receptor Antagonists AM6545 and AM4113 on Insulin Resistance in a High-Fructose High-Salt Rat Model of Metabolic Syndrome.

Background and Objectives: Insulin resistance (IR) is a serious condition leading to development of diabetes and cardiovascular complications. Hyper-activation of cannabinoid receptors-1 (CB1) has been linked to the development of metabolic disorders such as IR. Therefore, the effect of blocking CB1 on the development of IR was investigated in the present study. Materials and Methods: A 12-week high-fructose/high-salt feeding model of metabolic syndrome was used to induce IR in male Wistar rats. For this purpose, two different CB1-antagonists were synthesized and administered to the rats during the final four weeks of the study, AM6545, the peripheral neutral antagonist and AM4113, the central neutral antagonist. Results: High-fructose/salt feeding for 12 weeks led to development of IR while both AM6545 and AM4113, administered in the last 4 weeks, significantly inhibited IR. This was correlated with increased animal body weight wherein both AM6545 and AM4113 decreased body weight in IR animals but with loss of IR/body weight correlation. While IR animals showed significant elevations in serum cholesterol and triglycerides with no direct correlation with IR, both AM6545 and AM4113 inhibited these elevations, with direct IR/cholesterol correlation in case of AM6545. IR animals had elevated serum uric acid, which was reduced by both AM6545 and AM4113. In addition, IR animals had decreased adiponectin levels and elevated liver TNFα content with strong IR/adiponectin and IR/TNFα correlations. AM6545 inhibited the decreased adiponectin and the increased TNFα levels and retained the strong IR/adiponectin correlation. However, AM4113 inhibited the decreased adiponectin and the increased TNFα levels, but with loss of IR/adiponectin and IR/TNFα correlations. Conclusions: Both CB1 neutral antagonists alleviated IR peripherally, and exerted similar effects on rats with metabolic syndrome. They also displayed anti-dyslipidemic, anti-hyperurecemic and anti-inflammatory effects. Overall, these results should assist in the development of CB1 neutral antagonists with improved safety profiles for managing metabolic disorders.

Vitamin D3 potentiates the nephroprotective effects of metformin in a rat model of metabolic syndrome: role of AMPK/SIRT1 activation and DPP-4 inhibition.

The current study aimed to investigate the molecular mechanisms of metformin and vitamin D3-induced nephroprotection in a metabolic syndrome (MetS) rat model, evaluating the capacity of vitamin D3 to potentiate metformin action. MetS was induced by 10% fructose in drinking water and 3% salt in the diet. After 6 weeks, serum lipid profile and uric acid were measured, an oral glucose tolerance test (OGTT) was performed, and kidney function was investigated. In conjunction with the same concentrations of fructose and salt feeding, MetS rats with significant weight gain, dyslipidemia, hyperuricemia, and dysglycemia were treated orally with metformin (200mg/kg), vitamin D3 (10µg/kg), or both daily for 6 weeks. At the end of the study period, anthropometrical parameters were recorded, OGTT was reperformed, urine and blood samples were collected, and tissue samples were harvested at sacrifice. MetS rats showed dramatically declined renal function, enhanced intrarenal oxidative stress and inflammation, and extravagant renal histopathological damage with interstitial fibrosis. Metformin and vitamin D3 significantly reversed all the aforementioned deleterious effects in MetS rats. The study has verified the nephroprotective effects of metformin and vitamin D3 in MetS, accentuating the critical role of AMP-activated protein kinase/sirtuin-1 activation and dipeptidyl peptidase-4 inhibition. Given the synergistic effects of the combination, vitamin D3 is worth being investigated as an additional therapeutic agent for preventing MetS-induced nephropathy.

Characterization of the Nutritional Composition of a Biotechnologically Produced Oyster Mushroom and its Physiological Effects in Obese Zucker Rats.

Sustainable protein sources are needed to meet the increasing protein demands of a continuously growing world population. This study is focused on the biotechnological production of a protein rich oyster mushroom (Pleurotus sajor-caju; PSC) by valorization of an agricultural side stream and the evaluation of the physiological effects of PSC in a rat model of metabolic syndrome. PSC is produced via submerged cultivation in a 150 L bioreactor that utilizes isomaltulose molasses as its sole carbon source, and is further analyzed for its nutritional composition. A feeding trial is performed using Zucker rats which are fed a 5% PSC supplemented diet, for 4 weeks. Biochemical analyses reveal a significant reduction of the liver lipid concentrations and liver inflammation in the PSC fed obese rats in comparison to the obese rats from the control group. Hepatic qPCR analyses, differential transcript profiling, and enzyme activity measurements reveal a number of altered pathways that may be responsible for these anti-steatotic and anti-inflammatory effects of the mushroom. Bioconversion of a low quality agricultural side stream to an improved protein source is performed by submerged cultured PSC, and the obtained mycelium shows strong anti-steatotic and anti-inflammatory effects.

Sexual dimorphism in insulin resistance in a metabolic syndrome rat model.

ObjectiveWe assessed the sex-specific differences in the molecular mechanisms of insulin resistance in muscle and adipose tissue, in a MS rat model induced by a high sucrose diet.MethodsMale, female, and ovariectomized female Wistar rats were randomly distributed in control and high-sucrose diet (HSD) groups, supplemented for 24 weeks with 20% sucrose in the drinking water. At the end, we assessed parameters related to MS, analyzing the effects of the HSD on critical nodes of the insulin signaling pathway in muscle and adipose tissue.ResultsAt the end of the treatment, HSD groups of both sexes developed obesity, with a 15, 33 and 23% of body weight gain in male, female, and OVX groups respectively, compared with controls; mainly related to hypertrophy of peripancreatic and gonadal adipose tissue. They also developed hypertriglyceridemia, and liver steatosis, with the last being worse in the HSD females. Compared to the control groups, HSD rats had higher IL1B and TNFA levels and insulin resistance. HSD females were more intolerant to glucose than HSD males. Our observations suggest that insulin resistance mechanisms include an increase in phosphorylated AKT(S473) form in HSD male and female groups and a decrease in phosphorylated P70S6K1(T389) in the HSD male groups from peripancreatic adipose tissue. While in gonadal adipose tissue the phosphorylated form of AKT decreased in HSD females, but not in HSD males. Finally, HSD groups showed a reduction in p-AKT levels in gastrocnemius muscle.ConclusionA high-sucrose diet induces MS and insulin resistance with sex-associated differences and in a tissue-specific manner.

The role of resistin on metabolic syndrome-induced erectile dysfunction and thepossible therapeutic effect of Boldine.

Resistin is known as a potential mediator of obesity-associated insulin resistance. The high resistin level disrupts nitric oxide (NO)-mediated relaxation which is also important in erectile function. An antioxidant alkaloid, Boldine, is known as anti-diabetic and protects endothelial functions. We aimed to investigate resistin expression in penile tissue in the presence of insulin resistance (IR) and the effect ofBoldinetreatment on erectile functions in the metabolic syndrome (MetS) rat model. Wistar rats were randomly divided into three groups: Control, MetS, and boldine treated MetS group. MetS parameters were assessed by serum triglycerides (TG), uric acid (UA), glucose, insulin levels, HOMA index, and waist circumference (WC)/tibia length (TL) ratio. To evaluate erectile functions, intracavernous pressure (ICP)/mean arterial pressure (MAP) ratio was performed during cavernous nerve stimulation. Protein expressions of resistin, endothelial nitric oxide synthase (eNOS), p(S1177) eNOS, and insulin receptor-β were evaluated by Western blotting. TG, glucose, insulin levels, weight, WC/TL ratio, HOMA index and resistin expression in penile tissue were significantly increased and ICP/MAP values, and p (S1177) eNOS expression in penile tissue were decreased in MetS group. Boldine treatment enhanced ICP/MAP values, insulin receptor-β and p(S1177) eNOS expressions compared with the MetS group. MetS caused a deterioration in erectile function accompanied by an increase in resistin expression and a reduction in eNOS enzyme activation in the rat penile tissues. Boldine treatment resulted in an improvement in erectile function, independent of resistin expression.

Biochemical and histopathological assessment of liver in a rat model of metabolic syndrome induced by high-carbohydrate high-fat diet.

This study aimed to evaluate the oxidative stress status, antioxidants capacity, and presence of nonalcoholic fatty liver disease (NAFLD) in an animal model of MetS induced by high-carbohydrate high-fat (HCHF) diet. Male Wistar rats were randomized into two groups, assigned for two different types of diet (standard rat pellet or HCHF diet) for 20weeks. Liver was excised, weighed, and subjected to lipid peroxidation, nitric oxide (NO·) production, antioxidants activity, and histological assessment. The HCHF rats had higher lipid peroxidation and NO· level but lower enzymatic and nonenzymatic antioxidant levels than the normal animals. Histological evaluation revealed higher lobular inflammation, hepatocellular ballooning, NAFLD activity score, and lipid accumulation in the liver of HCHF group. In conclusion, the HCHF diet causes an increase in oxidative stress, depletion of antioxidants capacity, NAFLD, and liver injury. The induction of oxidative stress may be partially responsible for the development of NAFLD in MetS. PRACTICAL APPLICATIONS: The prevalence of MetS is estimated to increase rapidly with the escalating levels of obesity, diabetes, hypertension, and dyslipidemia. A suitable animal model of MetS that best mimicked the human disease state with known underlying mechanisms responsible for the pathogenesis of MetS is indispensable to search for potential adjunct therapies and drug targets. Thus, our current study elucidated the involvement of oxidative stress in linking MetS and NAFLD which might resemble the pathogenesis of MetS among Southeast Asian population.

Pulmonary vascular smooth muscle contraction in the rat model of metabolic syndrome

Metabolic syndrome is defined as a constellation of many metabolic disorders such as hypertension, impaired glucose tolerance, dyslipidemia and obesity, being this last disorder a key factor in the etiology of the syndrome. Animal model of metabolic syndrome allows us to study the phenomenology of disorders of cooperative interactions of effector cells responsible for regulating of the blood vessels tone. Here, we have characterized the metabolic, vascular changes in male Wistar rats fed on a high-fat, high-carbohydrate diet including lard (17%), fructose (17%) together with 20% fructose in drinking water, control rats were fed a standard rat chow. During 12 weeks on this diet, rats showed a change in body weight with impaired glucose tolerance. Vascular disorders included endothelial dysfunction in pulmonary artery.

Hydrogen inhalation alleviates nonalcoholic fatty liver disease in metabolic syndrome rats.

Hydrogen exhibits therapeutic and preventive effects against various diseases. The present study investigated the potential protective effect and dose-dependent manner of hydrogen inhalation on high fat and fructose diet (HFFD)-induced nonalcoholic fatty liver disease (NAFLD) in Sprague-Dawley rats. Rats were randomly divided into four groups: i) Control group, regular diet/air inhalation; ii) model group, HFFD/air inhalation; iii) low hydrogen group, HFFD/4% hydrogen inhalation; and iv) high hydrogen group, HFFD/67% hydrogen inhalation. After a 10-week experiment, hydrogen inhalation ameliorated weight gain, abdominal fat index, liver index and body mass index of rats fed with HFFD and lowered the total area under the curve in an oral glucose tolerance test. Hydrogen inhalation also ameliorated the increase in liver lipid content and alanine transaminase and aspartate transaminase activities. Liver histopathologic changes evaluated with hematoxylin and eosin as well as Oil Red O staining revealed lower lipid deposition in hydrogen inhalation groups, consistent with the decrease in the expression of the lipid synthesis gene SREBP-1c. The majority of the indicators were affected following treatment with hydrogen in a dose-dependent manner. In conclusion, hydrogen inhalation may play a protective role by influencing the general state, lipid metabolism parameters, liver histology and liver function indicators in the rat model of metabolic syndrome with NAFLD.

Roles of sarcoplasmic reticulum Ca2+ ATPase pump in the impairments of lymphatic contractile activity in a metabolic syndrome rat model

The intrinsic lymphatic contractile activity is necessary for proper lymph transport. Mesenteric lymphatic vessels from high-fructose diet-induced metabolic syndrome (MetSyn) rats exhibited impairments in its intrinsic phasic contractile activity; however, the molecular mechanisms responsible for the weaker lymphatic pumping activity in MetSyn conditions are unknown. Several metabolic disease models have shown that dysregulation of sarcoplasmic reticulum Ca2+ ATPase (SERCA) pump is one of the key determinants of the phenotypes seen in various muscle tissues. Hence, we hypothesized that a decrease in SERCA pump expression and/or activity in lymphatic muscle influences the diminished lymphatic vessel contractions in MetSyn animals. Results demonstrated that SERCA inhibitor, thapsigargin, significantly reduced lymphatic phasic contractile frequency and amplitude in control vessels, whereas, the reduced MetSyn lymphatic contractile activity was not further diminished by thapsigargin. While SERCA2a expression was significantly decreased in MetSyn lymphatic vessels, myosin light chain 20, MLC20 phosphorylation was increased in these vessels. Additionally, insulin resistant lymphatic muscle cells exhibited elevated intracellular calcium and decreased SERCA2a expression and activity. The SERCA activator, CDN 1163 partially restored lymphatic contractile activity in MetSyn lymphatic vessel by increasing phasic contractile frequency. Thus, our data provide the first evidence that SERCA2a modulates the lymphatic pumping activity by regulating phasic contractile amplitude and frequency, but not the lymphatic tone. Diminished lymphatic contractile activity in the vessels from the MetSyn animal is associated with the decreased SERCA2a expression and impaired SERCA2 activity in lymphatic muscle.

Serum biochemical and inflammatory cytokines in a rat model of metabolic syndrome

Background: Metabolic syndrome (MetS) is a combination of cardio-metabolic risk factors including obesity, hyperglycaemia, dyslipidaemia, oxidative stress and hypertension. 
 Aims and Objectives: This study was aimed at determining the serum concentrations of biochemical and inflammatory cytokines and assesses the correlation between the biochemical and inflammatory cytokines in a rat model of metabolic syndrome.
 Materials and Methods: Twenty rats were divided into 2 groups of 10 each: control (fructose untreated) and the fructose treated group. MetS was induced by oral administration of 10% fructose in water for 32 weeks. At the end of the experiment, rats were fasted for 12 hours and blood samples collected and body weight, body mass index (BMI), fasting blood glucose (FBG), serum lipid profile, interleukin-6 (IL-6), interleukin-10 (IL-10), tumour necrosis factor-α (TNF-α) were measured using standard techniques.
 Result: Result indicated significantly (P< 0.05) increased FBG, body weight, BMI, serum TC and LDL-C while, HDL-C levels significantly (P< 0.05) decreased in MetS group compared with controls. However, the levels of VLDL-C, TG and AIX were not significantly (P > 0.05) different between the groups. Significantly (P< 0.05) increased serum IL-6, IL-10 and TNF-α were observed in MetS group compared with controls. Serum IL-10 and TNF- α were inversely correlated with BMI. Serum IL-10 negatively correlated with FBG while, IL-6 was not correlated with either of BMI and FBG.Serum AIX and VLDL-C were positively correlated with TG while, HDL-C level was inversely correlated with TG. With the exception of serum LDL-C which positively correlated with TC, significant correlation was not established between serum TC and each of AIX, HDL-C and VLDL-C.
 Conclusion: The rat model of MetS was established after treatment with 10% fructose in water. This plays an important role in the pathogenesis of components of metabolic syndrome, including dyslipidaemia, hyperglycaemia and obesity; and serum IL-6, IL-10 and TNF- α are raised in metabolic syndrome and this underscores the role of these cytokines in inflammation associated with metabolic syndrome.

Cover Image

Cover caption The cover image is based on the Original Article “Short- And Long-Term Administration of Imeglimin Counters Cardiorenal Dysfunction in a Rat Model of Metabolic Syndrome by Marianne Lachaux et al., https://doi.org/10.1002/edm2.128”.

Hesperidin ameliorates signs of the metabolic syndrome and cardiac dysfunction via IRS/Akt/GLUT4 signaling pathway in a rat model of diet-induced metabolic syndrome.

Hesperidin has been reported to have biological activities such as antihypertensive, hypoglycemic, and antioxidant effects. This study investigated whether hesperidin could improve signs of the metabolic syndrome and cardiac function in a high-fat diet (HFD) induced metabolic syndrome (MS) in rats. Male Sprague-Dawley rats were fed HFD and 15% fructose for 16weeks and treated with hesperidin (15 or 30mg/kg, based on signs of MS from a preliminary study) or metformin, a positive control agent, (100mg/kg) for the final four weeks. Cardiac function, blood pressure, fasting blood glucose, oral glucose tolerance, serum insulin, and lipid profiles were measured. Histomorphometrics of left ventricles, epidydimal fat pads and liver were evaluated. Expressions of phosphorylate insulin receptor substrate1(p-IRS1), p-Akt and GLUT4 in cardiac tissue were determined. Hesperidin and metformin attenuated MS in HFD rats (p < 0.05). The accumulation of visceral fat pads and fatty liver associated with increases in liver lipid contents and liver enzymes were found in MS rats that were alleviated in hesperidin or metformin-treated groups (p < 0.05). Hesperidin and metformin improved cardiac dysfunction and hypertrophy observed in MS rats (p < 0.05). Restoration of the insulin signaling pathway, IRS/Akt/GLUT4 protein expression, was demonstrated in hesperidin and metformin-treated groups (p < 0.05). Hesperidin (30mg/kg) was more effective than the lower dose. Hesperidin was effective in reducing signs of MS and alterations of LV hypertrophy and function. These beneficial effects on the heart were associated with the restoration of the cardiac insulin signaling pathway in MS rats.