Dysfunction In Obese Rats Research Articles

Effects evaluation of different exercises on subclinical left ventricular dysfunction in obese rats by speckle-tracking echocardiography

ObjectiveTo identify subclinical left ventricle dysfunction (LVD) in obese rats by speckle-tracking echocardiography, and to evaluate the effects of 12-week Moderate-Intensity Continuous Training (MICT) or High-Intensity Interval Training (HIIT) on LV geometry, histology and function in obese rats. MethodsEighteen male standard or obese Sprague-Dawley rats were randomly divided into the Control group, the MICT group, and the HIIT group. Exercise interventions were conducted for 12 weeks, with equal total load and increased intensity gradient. Using dual-energy X-ray, two-dimensional speckle-tracking echocardiography, pulse Doppler, and HE staining to evalucate body shape, LV morphology, structure, and myocardial mechanics function. Results(1) Both MICT and HIIT have good weight loss shaping effect. (2) The LV of obese rats underwent pathological remodeling, with decreased longitudinal contractility and synchrony, and increased circumferential contractility and synchrony. (3) Exercise can inhibit LV pathological remodeling, improve myocardial mechanical function. HIIT is superior to MICT. (4) The global longitudinal strain of obese rats in the HIIT group showed a significant correlation with Fat% and Lean%. ConclusionObesity can induce LV pathological remodeling and subclinical dysfunction. Compared with MICT, 12-week HIIT can effectively inhibit the pathological remodeling of LV and promote the benign development of myocardial mechanical function in obese rats.

Citrus bergamia (EndoBerg®) attenuates systolic blood pressure and prevents cardiac oxidative stress, cardiac remodeling and dysfunction in obese rats

Citrus bergamia (EndoBerg®) attenuates systolic blood pressure and prevents cardiac oxidative stress, cardiac remodeling and dysfunction in obese rats

Evaluation of Expression of Cytochrome P450 Aromatase and Inflammatory, Oxidative, and Apoptotic Markers in Testicular Tissue of Obese Rats (Pre)Treated with Garlic Powder.

Today, adolescent obesity is recognized as an epidemic and a cause of reproductive disorders. Decreased testosterone levels occur due to functional defects in the hypothalamus-pituitary axis, excessive activity of cytochrome P450 aromatase enzyme, and testicular dysfunction in these people. Oxidative damage, inflammation, and apoptosis are also the main mechanisms of testicular damage during obesity. The use of herbal products such as garlic can improve this disorder due to its anti-inflammatory and antioxidant properties. Therefore, the aim of this study is to investigate the effect of pretreatment and treatment of garlic powder on the expression of cytochrome P450 aromatase enzyme and the expression of genes involved in testosterone synthesis, inflammation, oxidative damage, apoptosis in testicular tissue, and metabolic function of liver tissue in young male obese rats. Eighty male Wistar rats were divided into the controlled and treated groups. Serum levels of lipid, glucose, and insulin as metabolic factors were measured along with the testicular antioxidant and inflammation markers. The expression of Bcl2, Bax, and caspase-3 along with NF-κB, SREBP-1c, CPT-1beta, Nrf-2, CD36, FAS, CYP19A1, P450scc, StAR, 17βHSD, PPARα, and aromatase (CYP19, P450arom) was also measured. Testicular histological evaluation and spermatogenic process was also performed. The results showed that oxidative, inflammatory, and metabolic factors significantly increased in obese rats. The testicular expression of aromatase, NF-κB, Bax, and caspase 3 increased and Nrf2 expression decreased in obese rats, while (pre) treatment with garlic powder significantly decreased the expression of these genes in obese rats. These results were also confirmed by the findings of the histological evaluation and sperm analysis. It can be concluded that garlic powder could improve reproductive dysfunction in obese rats.

Time-Restricted Feeding Improved Vascular Endothelial Function in a High-Fat Diet-Induced Obesity Rat Model.

Obesity, where there is enhancement of stored body fat in adipose tissues, is associated with cardiovascular complications that are mainly related to atherosclerosis. Time-restricted feeding (TRF) is a form of restricted eating aimed at reducing weight in obese subjects. The present study aims to investigate changes in vascular endothelial function, endothelial nitric oxide synthase (eNOS), and protein kinase B (Akt) protein expressions with TRF in obese and normal rats. Male Sprague Dawley rats were divided into two normal and three obese groups; obesity was induced in the obese groups by feeding with a high-fat diet (HFD) for six weeks. After six weeks, rats were equally divided into five groups (n = 7 per group): Normal group (NR) which continued on a standard diet for six more weeks, normal group switched to TRF with a standard diet for six weeks (NR + TRFSD), obese group (OR) which continued on HFD for six more weeks, obese group switched to TRF of HFD (OR + TRFHFD), and obese group switched to TRF of a standard diet (OR + TRFSD). TRF was practiced for six weeks, after which the rats were sacrificed. Aortic endothelium-dependent and endothelium-independent relaxations and contractions were assessed using the organ bath. Aortic eNOS and Akt protein expressions were determined using immunoblotting. Fasting blood glucose, body weight, body mass index (BMI), serum lipid profile, Lee’s index, serum insulin levels, and sensitivity (HOMA-IR) were also measured. Endothelium-dependent relaxation was significantly impaired, while endothelium-dependent contraction increased in obese rats compared to that in normal rats. Both obese groups which underwent TRF with a HFD and standard diet improved their impairments in endothelium-dependent relaxation and reduced endothelium-dependent contraction; these were associated with increased expressions of aortic eNOS and Akt protein. Both obese groups with TRF reduced body weight, BMI, Lee’s index, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and improved insulin sensitivity. TRF improved endothelium-dependent relaxation and reduced endothelium-dependent contraction, thus attenuating endothelial dysfunction in obese rats. These were associated with increased aortic eNOS and Akt protein expressions.

Investigation of the Effect of Lycopene, Hesperidin, Essential Oil and their Relative Nano-Formulation Form on Experimentally Obese –Induced Rats

The study was designed to investigate the effect of lycopene, hesperidin, and essential oil and their nano-formulation form in high-fat diet (HFD) -induced obese Wistar rats. To achieve this, a total of ninety adult Wistar male rats were used. The animals were made obese by feeding rats' high-fat diet (HFD, cholesterol, and bile acid). A dose of cholesterol (30 mg/0.3 mL olive oil /1 kg b.w.) was orally administrated (five times per week ) for 8 consecutive weeks. Obesity was confirmed by the percentages of body weight gain. Animals were divided into negative control groups (normal rats received normal diet) and positive control groups (normal rats received HFD ) and treatment groups (obese rats received different samples) of five animals each. Dose of lycopene and its nanoparticles 50 mg/kg b. wt., hesperidin, essential oil, and their nano-formulation form (100 mg/kg b.wt). All samples and standard drug (orlistat 12 mg/kg b. wt.) were orally administered once daily for four weeks. At the end of experiement, all animal groups were sacrificed and blood samples were collected. Different parameters including total cholesterol, triglycride, HDL-cholesterol, total lipid, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), creatinene and urea were determined in the serum. The liver tissue was excised for the determination of hepatic antioxidant biomarkers (catalase and GSH) and oxidative stress (lipid peroxide). Histopathological examination of liver tissue of obese rats showed diffuse fatty liver, circumscribed hepatic vacuoles with prepheralnucleous. However, obese rats- treated with all different samples declaring amelioration in all the measured parameters. The results obtained illustrated that the nano-formulation form are more effective than a native form of lycopene, hesperidin, and essential oil. Besides, the lycopene and its nanoparticles were more effective than hesperidin, essential oil, and their nano-formulation forms. So, it could be concluded that , oral supplementation with lycopene, hesperidin, essential oil, and their relative nano-formulation forms can treat hepatic dysfunction in obese rats.

Pioglitazone prevents obesity-related airway hyperreactivity and neuronal M2 receptor dysfunction.

Obesity-related asthma often presents with more severe symptoms than non-obesity-related asthma and responds poorly to current treatments. Both insulin resistance and hyperinsulinemia are common in obesity. We have shown that increased insulin mediates airway hyperreactivity in diet-induced obese rats by causing neuronal M2 muscarinic receptor dysfunction, which normally inhibits acetylcholine release from parasympathetic nerves. Decreasing insulin with streptozotocin prevented airway hyperreactivity and M2 receptor dysfunction. The objective of the present study was to investigate whether pioglitazone, a hypoglycemic drug, prevents airway hyperreactivity and M2 receptor dysfunction in obese rats. Male rats fed a low- or high-fat diet were treated with pioglitazone or PBS by daily gavage. Body weight, body fat, fasting insulin, and bronchoconstriction and bradycardia in response to electrical stimulation of vagus nerves and to aerosolized methacholine were recorded. Pilocarpine, a muscarinic receptor agonist, was used to measure M2 receptor function. Rats on a high-fat diet had potentiated airway responsiveness to vagal stimulation and dysfunctional neuronal M2 receptors, whereas airway responsiveness to methacholine was unaffected. Pioglitazone reduced fasting insulin and prevented airway hyperresponsiveness and M2 receptor dysfunction but did not change inflammatory cytokine mRNA expression in alveolar macrophages. High-fat diet, with and without pioglitazone, had tissue-specific effects on insulin receptor mRNA expression. In conclusion, pioglitazone prevents vagally mediated airway hyperreactivity and protects neuronal M2 muscarinic receptor function in obese rats.

Effect of spexin on renal dysfunction in experimentally obese rats: potential mitigating mechanisms via galanin receptor-2

This study declared effect of spexin (SPX) on renal dysfunction in obese rats and its potential mitigating mechanisms which could mediated via galanin receptor-2 (GALR-2). Thirty two 32 Wistar male rats were arranged into four groups: control, high fat/fructose diet (HFFD), HFFD + SPX and HFFD + M871 (galanin receptor 2 antagonist)+SPX. At the termination of the experiment, urine volume, body mass index, Lee index and mean arterial blood pressure were assessed. Renal function was evaluated. Lipid profile, fasting glucose, insulin, insulin resistance and SPX levels were estimated. Also, renal histopathological, immunohistochemical and relative gene expression of renal tissue were done. Also, renal protein carbonyl, reduced glutathione, interferon gamma, monocyte chemoattractant protein-1, interleukin-10 and hydroxyproline were determined. Our results explored that SPX treatment prominently mitigated the metabolic changes and renal dysfunction induced by HFFD via GALR-2. SPX improved insulin resistance, dyslipidemia, renal oxidative stress, inflammation, apoptosis, and fibrosis. So, SPX can be considered as prospective therapeutic agent for treating renal dysfunction.

Echography analysis of musculoskeletal, heart and liver alterations associated with endothelial dysfunction in obese rats

BackgroundModern imaging plays a central role in the care of obese patients, and there is an integral focus on its use and accessibility in individuals who have alterations of various in various organs. The objective in this study was to perform an echographic analysis of musculoskeletal system disorders, endothelial dysfunction and the left ventricle (LV) in obese rats.MethodsSprague Dawley rats (250 ± 5 g) were obtained and divided into two groups: the control (C) group was fed with a standard diet, and the obese (Ob) group was fed hyper caloric diet with a high fructose-fat content for 4 months. Body weight, cholesterol, triglycerides, glucose, inflammatory cytokines and adhesion molecules (ICAM-1, VCAM-1) were measured. Additionally, two-dimensional echocardiography, abdominal ultrasound and musculoskeletal system studies were performed in the lower extremities.ResultsThe body weight in the Ob group was increased compared to that in the control group, (p < 0.001); in addition, increased glucose, cholesterol and triglyceride concentrations (p < 0.05) as well as increased levels of the adhesion molecules ICAM-1 and, VCAM-1 (p < 0.01) were found in the Ob group vs the C group. On ultrasound, 75% of the Ob group presented fatty liver and distal joint abnormalities.ConclusionObese rats exhibit endothelial dysfunction and musculoskeletal changes, also, fatty liver and articular cysts in the posterior region of the distal lower- extremity joints.

A combination of an antioxidant with a prebiotic exerts greater efficacy than either as a monotherapy on cognitive improvement in castrated-obese male rats.

Previous studies by ourselves and others have demonstrated that both obesity and testosterone deprivation have been related to cognitive decline. We have also shown that a prebiotic and n-acetyl cysteine (NAC) improved cognitive dysfunction in obese rats and castrated-male rats. However, the effects of NAC, a prebiotic (inulin), and a combination of the two on cognition in castrated-obese rats has never been investigated. The hypothesis was that NAC and inulin attenuated cognitive decline in castrated-obese rats by improving gut dysbiosis, and decreasing oxidative stress, glial activation and apoptosis. Male Wistar rats (n = 36) were fed with either a normal diet (ND: n = 6) or a high-fat diet (HFD: n = 30) for twenty-eight weeks. The resultant obese rats had a bilateral orchiectomy (ORX) and were randomly divided into five subgroups (n = 6/ subgroup). Each subgroup was treated with one of five therapies: a vehicle; testosterone replacement (2mg/kg/day); NAC (100mg/kg); inulin (10%, w/w), or a combination of the NAC and inulin for four weeks. The results demonstrated that castrated-obese rats developed gut dysbiosis, metabolic disturbance, brain pathologies, and cognitive decline. All of the pathological conditions in the brain were ameliorated to an equal extent by testosterone replacement, NAC, and inulin supplementation. Interestingly, a combination of NAC and inulin had the greatest beneficial effect on cognitive function by synergistically reducing hippocampal inflammation and ameliorating glial dysmorphology. These findings suggest that a combination of NAC and inulin may confer the greatest benefits in improving cognitive function in castrated-obese male rats.

Beneficial Effects of Low-Calorie-Carbohydrate/High-Agar Diet on Cardiometabolic Disorders Associated with Non-Alcoholic Fatty Liver Disease in Obese Rats.

Energy restriction and low carbohydrate diets are recommended as nutrition therapies to prevent becoming overweight or obese. However, their beneficial effects in non-alcoholic fatty liver disease (NAFLD) are less well investigated. In addition, the effects of the type of polysaccharides incorporated into these diets and their contents have been scarcely studied. Therefore, this study aimed to elucidate whether low-calorie-carbohydrate high-agar diets could improve liver metabolic dysfunction, membrane fluidity, oxidative damage, and endothelial dysfunction in obese rats. Obesity was induced by feeding rats a high-fat diet (HFD) for 10 weeks. The obese rats were then divided into two homogenous groups: the first group was fed low-calorie-carbohydrate/high-agar diet (LCC/HA) and the second continued to consume the HFD for 4 weeks [obese control (Ob-C)]. Normo-ponderal rats were fed a normal diet during the entire study, and were used as the control (N-C). Compared with the Ob-C group, body weight, hepatic lipids, low density lipoproteins cholesterol (C), the non esterified cholesterol/phospholipids ratio, serum transaminases activities, and lipid peroxidation markers (thiobarbituric acid reactive substances and lipid hydroperoxides) were reduced in LCC/HA group (P<0.05). However, the serum concentration of high density lipoproteins-C was enhanced (P<0.05). In addition, we observed improved antioxidant defence and endothelial dysfunction associated with antioxidant enzymes, such as superoxide dismutase, glutathione peroxidase, and catalase (P<0.05), and nitric oxide level (P<0.05). These findings suggest that hypocaloric diets low in energy and carbohydrates and rich in agar may be beneficial against HFD-induced hepatic steatosis damage, and may be a promising therapeutic strategy to counteract NAFLD development associated with obesity.

The ameliorating effect of carotenoid rich fraction extracted from Dunaliella salina microalga against inflammation- associated cardiac dysfunction in obese rats

The carotenoid rich fraction of microalgae Dunaliella salina (crf-DS) have been receiving great attention, due to they abilities to protect and improve various disorders. The objective of this study is to explore the therapeutic efficiency of crf-DS on obesity-assciated cardiac dysfunction in the high-fat diet (HFD) treated rats. These rats were orally administered with crf-DS (150 mg /kg body weight), for six consecutive weeks in comparison with reference drug(orlistat). Specific cardiac biomarkers were examined including; adiponectin, plasminogen activator inhibitor (PAI-1), glucagon, troponin-I (cTnI). The cell adhesion molecules (VCAM and ICAM), C-reactive protein (CRP), collagen type II (Col II), collagen alpha-1 (III) chain (Col3A1), lipoxygenase activity (LOX), as well as histopathological examination of cardiac tissue were investigated. Results indicated a significant reduction(P ≤ 0.05) in adiponectin and glucagon levels in serum of obese rats. However, cTnI, PAI-1, cell adhesion molecules, CRP, Col II, and Col3A1 and LOX levels declared marked increase. Histopathological examination of cardiac tissue showed fibrosis with severe congestion in the myocardial blood vessels. On the other hand, rats medicated with a crf-DS demonstrated noticeable ameliorating effect in all the measured parameters. Beside, myocardial tissue of obese rats showed no alteration. Hence, It could be concluded that, oral supplementation with crf-DS is able to attenuate cardiac dysfunction in obese rats. Further extended work is needed to exploit, the possible application of D. salina as nutraceuticals and food additives.

Brazilian Curcuma longa L. attenuates comorbidities by modulating adipose tissue dysfunction in obese rats

BackgroundAdipose tissue dysfunction is a condition characterized by inflammation and oxidative stress able to lead metabolic disorders. Curcuma longa L. (Cl) is a rhizome commonly used in Indian culinary which presents anti-inflammatory and antioxidant compounds. The aim of this study was to evaluate the effect of in natura Curcuma longa L. on adipose tissue dysfunction and comorbidities in obese rats.MethodsMale Wistar rats (8 weeks old, n = 16) received standard chow + fructose in drinking water (30%) ad libitum for 16 weeks. After this period, animals were randomly divided to receive placebo treatment (fructose, n = 8) or Curcuma longa L. treatment (fructose + Cl, n = 8) for more 8 weeks, totalizing 24 weeks of experiment. Curcuma longa L. was mixed in water and gave to the animals by gavage in a dose of 80 mg/kg of body weight. Body composition, systolic blood pressure, metabolic, hormonal, inflammatory, and oxidative stress analysis were performed in plasma and adipose tissue.ResultsCurcuma longa L. reduced adiposity index and adipocyte hypertrophy, improved insulin resistance and systolic blood pressure, and reduced inflammation and oxidative stress in adipose tissue.ConclusionCurcuma longa L. in natura is able to modulate adipose tissue dysfunction, avoiding the development of comorbidities. It can be considered a phytochemical treatment strategy against obesity-related chronic diseases.

Effect of 3,4-dihydroxyacetophenone on endothelial dysfunction in obese rats

Context: 3,4-Dihydroxyacetophenone (DHAP) has been reported to possess cardiovascular pharmacological effects.Objective: This study was designed to determine whether DHAP could improve endothelial function in obese rats.Materials and methods: Wistar rats were randomly divided into control, obesity, and DHAP groups and fed a normal, high-fat, and high-fat plus DHAP (10 mg kg−1 d−1) diet, respectively, for 8 weeks. Endothelial-dependent vasodilatation was assessed. Endothelial nitric oxide synthase (eNOS) activity and nitric oxide (NO) production in endothelial cells were determined. Nuclear transcription factor kappa B (NF-κB) expression and superoxide production in aorta were evaluated.Results: DHAP treatment significantly decreased plasma triglycerides (0.94 ± 0.31 mmol/l versus 1.36 ± 0.29 mmol/l, p < 0.05) and free fatty acids (0.53 ± 0.15 mmol/l versus 0.99 ± 0.24 mmol/l, p < 0.05), reduced serum tumor necrosis factor α (35.56 ± 9.28 pg/ml versus 68.3 ± 10.24 pg/ml, p < 0.05) and malondialdehyde (2.94 ± 0.58 pg/ml versus 6.45 ± 0.70 pg/ml, p < 0.05), and increased serum adiponectin levels (164.5 ± 34.5 μg/l versus 84.5 ± 20.4 μg/l, p < 0.05). DHAP enhanced endothelial-dependent vasodilatation and improved endothelial function in obese rats (p < 0.05). eNOS activity and NO production in endothelial cells significantly decreased and NF-κB activation and superoxide production in aorta significantly increased in obese rats compared with the control group (p < 0.05). However, DHAP treatment significantly up-regulated the eNOS–NO pathway and decreased NF-κB activation and superoxide production (p < 0.05).Conclusion: DHAP improved endothelial function in obese rats. This beneficial effect may be associated with up-regulation of the eNOS–NO pathway by improving lipid metabolism and reducing oxidative stress and inflammation activity.

Exercise training starting at weaning age preserves cardiac pacemaker function in adulthood of diet-induced obese rats.

Peripheral sympathetic overdrive in young obese subjects contributes to further aggravation of insulin resistance, diabetes, and hypertension, thus inducing worsening clinical conditions in adulthood. Exercise training has been considered a strategy to repair obesity autonomic dysfunction, thereby reducing the cardiometabolic risk. Therefore, the aim of this study was to assess the effect of early exercise training, starting immediately after weaning, on cardiac autonomic control in diet-induced obese rats. Male Wistar rats (weaning) were divided into four groups: (i) a control group (n = 6); (ii) an exercise-trained control group (n = 6); (iii) a diet-induced obesity group (n = 6); and (iv) an exercise-trained diet-induced obesity group (n = 6). The development of obesity was induced by 9 weeks of palatable diet intake, and the training program was implemented in a motor-driven treadmill (5 times per week) during the same period. After this period, animals were submitted to vein and artery catheter implantation to assess cardiac autonomic balance by methylatropine (3 mg/kg) and propranolol (4 mg/kg) administration. Exercise training increased running performance in both groups (p < 0.05). Exercise training also prevented the increased resting heart rate in obese rats, which seemed to be related to cardiac pacemaker activity preservation (p < 0.05). Additionally, the training program preserved the pressure and bradycardia responses to autonomic blockade in obese rats (p < 0.05). An exercise program beginning at weaning age prevents cardiovascular dysfunction in obese rats, indicating that exercise training may be used as a nonpharmacological therapeutic strategy for the treatment of cardiometabolic diseases.

Determinants of atrial fibrillation in an animal model of obesity and acute obstructive sleep apnea

Obesity and obstructive sleep apnea (OSA) are risk factors for atrial fibrillation (AF), but the underlying mechanisms are poorly understood. The purpose of this study was to assess the mechanisms underlying AF promotion by obesity and OSA in rat models. Zucker obese rats (ORs) and lean rats (LRs) were intubated and ventilated with air and 2% isoflurane. OSA was mimicked by stopping the ventilator and closing the airway for 40 seconds. For nonobstructive control periods, the protocol was repeated with an open airway. Fifteen seconds after apnea onset, AF susceptibility was tested with 6 atrial burst pacing cycles (25 Hz, 3 seconds, 1-second intercycle pauses). AF was not inducible in ORs or LRs at baseline or in nonobstructive control periods. AF was induced in 24 of 28 ORs (85.7%) vs 5 of 18 LRs (27.8%) during obstructive apnea (P <.001). Negative intrathoracic pressure generation (esophageal pressure monitoring) was substantial during obstructive apnea. Echocardiography showed left ventricular hypertrophy with diastolic dysfunction in ORs. Obstructive apnea caused acute left atrial (LA) dilation, increasing LA diameter significantly more in ORs than in LRs. To clarify AF mechanisms, 24 AF-inducible ORs were divided into 4 groups: saline (n = 5), pharmacologic autonomic blockade (n = 7), respiratory muscle paralysis with rocuronium (n = 6), and inferior vena cava (IVC) balloon occlusion to unload the LA (n = 6). Balloon catheter-induced IVC occlusion prevented LA distension during obstructive apnea, leading to 83.3% AF prevention (P <.05). Rocuronium also was protective (66.7%), but autonomic blockade had smaller effects (42.9% prevention). Obesity and acute obstructive apnea interacted to promote AF in this model. Forced inspiration-induced acute LA distension related to diastolic dysfunction may be an important component of the arrhythmogenic substrate for AF during OSA episodes in obese patients.

High free fatty acids level related with cardiac dysfunction in obese rats

AimTo determine whether reducing free fatty acids (FFAs) concentration has a protective effect on cardiac structure and function in high-fat-diet-induced obese rat. MethodsSprague–Dawley rats were randomly divided into normal control, obesity and fenofibrate group. After 8 or 16 weeks, the maximum velocity of myocardial contraction (+dP/dt) and diastole (−dP/dt) were measured. The concentrations of triglyceride, FFAs and angiotensin II were measured. Mitochondrial cytochrome C release and protein levels of NF-kappa B (NF-κB) and inducible nitric oxide synthase (iNOS) in myocardium were analyzed. ResultsThe triglyceride, FFAs and angiotensin II levels were significantly higher in circulating and myocardium in obese rats, associated with lipid deposition, increased mitochondrial cytochrome C release and protein levels of NF-κB and iNOS in myocardium. These alterations were reversed by fenofibrate, in parallel with improvement in +dP/dt, −dP/dt and ultrastructures of myocardial mitochondrion. The cardiac dysfunctions had negative correlation with intramyocardial lipid deposition, FFAs, angiotensin II, and protein levels of NF-κB and iNOS. ConclusionCardiac dysfunction of obese rats could be improved by reducing FFAs level. Intramyocardial lipid accumulation may increase the risk of heart failure in obese rats by increasing renin–angiotensin systems activity and protein levels of NF-κB and iNOS in myocardium.

Involvement of L‐type calcium channel and serca2a in myocardial dysfunction induced by obesity

Obesity has been shown to impair myocardial performance. Nevertheless, the mechanisms underlying the participation of calcium (Ca(2+) ) handling on cardiac dysfunction in obesity models remain unknown. L-type Ca(2+) channels and sarcoplasmic reticulum (SR) Ca(2+) -ATPase (SERCA2a), may contribute to the cardiac dysfunction induced by obesity. The purpose of this study was to investigate whether myocardial dysfunction in obese rats is related to decreased activity and/or expression of L-type Ca(2+) channels and SERCA2a. Male 30-day-old Wistar rats were fed standard (C) and alternately four palatable high-fat diets (Ob) for 15 weeks. Obesity was determined by adiposity index and comorbidities were evaluated. Myocardial function was evaluated in isolated left ventricle papillary muscles under basal conditions and after inotropic and lusitropic maneuvers. L-type Ca(2+) channels and SERCA2a activity were determined using specific blockers, while changes in the amount of channels were evaluated by Western blot analysis. Phospholamban (PLB) protein expression and the SERCA2a/PLB ratio were also determined. Compared with C rats, the Ob rats had increased body fat, adiposity index and several comorbidities. The Ob muscles developed similar baseline data, but myocardial responsiveness to post-rest contraction stimulus and increased extracellular Ca(2+) was compromised. The diltiazem promoted higher inhibition on developed tension in obese rats. In addition, there were no changes in the L-type Ca(2+) channel protein content and SERCA2a behavior (activity and expression). In conclusion, the myocardial dysfunction caused by obesity is related to L-type Ca(2+) channel activity impairment without significant changes in SERCA2a expression and function as well as L-type Ca(2+) protein levels.

Exercise reduces oxidative stress but does not alleviate hyperinsulinemia or renal dopamine D1receptor dysfunction in obese rats

Impairment of renal dopamine D1 receptor (D1R)-mediated natriuresis is associated with hypertension in humans and animal models, including obese Zucker rats. We have previously reported that treatment of these rats with antioxidants or insulin sensitizers reduced insulin levels and oxidative stress, restored D1R-mediated natriuresis, and reduced blood pressure. Furthermore, the redox-sensitive transcription factor, nuclear factor-κB (NF-κB), has been implicated in impairment of D1R-mediated natriuresis during oxidative stress. In this study, we investigated the effect of exercise on insulin levels, oxidative stress, nuclear translocation of NF-κB, blood pressure, albuminuria, and D1R-mediated natriuresis. The exercise protocol involved treadmill exercise from 3 wk of age for 8 wk. Exercise reduced oxidative stress, nuclear translocation of NF-κB, and albuminuria. However, exercise did not reduce plasma insulin levels or blood pressure. Also, selective D1R agonist (SKF-38393)-mediated increases in sodium excretion and guanosine 5'-O-(3-thiotriphosphate) binding were impaired in obese rats compared with lean rats, and exercise did not restore this defect. We conclude that, while exercise is beneficial in reducing oxidative stress and renal injury, reducing insulin levels may be required to restore D1R-mediated natriuresis in this model of obesity and metabolic syndrome. Furthermore, this study supports previous observations that restoring D1R function contributes to blood pressure reduction in this model.

Does our fat tell our brain what to do? A ‘sympathetic’ appraisal

Does our fat tell our brain what to do? A ‘sympathetic’ appraisal

Adiponectin directly improves endothelial dysfunction in obese rats through the AMPK–eNOS Pathway

Hypoadiponectinemia has been proved to be closely related to endothelial dysfunction in peripheral arteries and is thought to be an independent risk factor for cardiovascular disease. The objective of this study was to investigate whether adiponectin might independently improve endothelial dysfunction in aorta isolated from high-fat-diet-induced obese. Sprague-Dawley rat and to study the mechanism involved. Male Sprague-Dawley rats were fed with a regular or a high-fat diet for 6 weeks. The aorta was isolated, and vascular segments were incubated with vehicle or the globular adiponectin (globular domain (gAD); 2 mg ml(-1)) for 2 h. The effect of gAD on endothelial function and nitric oxide (NO) production was determined. Human aortic endothelial cells in primary culture were treated with vehicle or gAD (4 mg ml(-1)). The effect of gAD on the level of phosphorylation of endothelial nitric oxide synthase (eNOS) at Ser1177, AMPK at Thr176 and Akt at Ser473 in endothelial cells were determined. Severe endothelial dysfunction was observed in high-fat diet fed rat aortic segments. After gAd incubation, the endothelium-dependent relaxation was partly improved and total production of nitric oxide as result of enhanced eNOS activity was also increased. In the cultured endothelial cell line HUVEC, globular adiponectin increased the activity of eNOS through activating AMPK by stimulating its phosphorylation at Thr176 but not Akt. The demonstration in the current study that adiponectin reverses endothelial dysfunction through increasing NO production by eNOS phosphorylation, and decreasing NO inactivation by blocking superoxide production provides a new direction in the prevention of vascular injury in the obesity population.