Obese Male Rats Research Articles

Zingiber officinale extract maximizes the efficacy of simvastatin as a hypolipidemic drug in obese male rats.

Obesity became a serious public health problem with enormous socioeconomic implications among the Egyptian population. The present investigation aimed to explore the efficacy of Zingiber officinale extract as a hypolipidemic agent combined with the commercially well-known anti-obesity drug simvastatin in obese rats. Thirty-five male Wister rats were randomly divided into five groups as follows: group I received a standard balanced diet for ten weeks; high-fat diet was orally administered to rats in groups II-V for ten weeks. From the fifth week to the tenth week, group III orally received simvastatin (40 mg/kg B.W.), group IV orally received Z. officinale root extract (400 mg/kg B.W.), and group V orally received simvastatin (20 mg/kg B.W.) plus Z. officinale extract (200 mg/kg B.W.) separately. Liver and kidney function tests, lipid profiles, serum glucose, insulin, and leptin were determined. Quantitative RT-PCR analysis of PPAR-γ, iNOS, HMG-CoA reductase, and GLUT-4 genes was carried out. Caspase 3 was estimated in liver and kidney tissues immunohistochemically. Liver and kidney tissues were examined histologically. The administration of Z. officinale extract plus simvastatin to high-fat diet-fed rats caused a significant reduction in the expression of HMG-coA reductase and iNOS by 41.81% and 88.05%, respectively, compared to highfat diet (HFD)-fed rats that received simvastatin only. Otherwise, a significant increase was noticed in the expression of PPAR-γ and GLUT-4 by 33.3% and 138.81%, respectively, compared to those that received simvastatin only. Immunohistochemistry emphasized that a combination of Z. officinale extract plus simvastatin significantly suppressed caspase 3 in the hepatic tissue of high-fat diet-fed rats. Moreover, the best results of lipid profile indices and hormonal indicators were obtained when rats received Z. officinale extract plus simvastatin. Z. officinale extract enhanced the efficiency of simvastatin as a hypolipidemic drug in obese rats due to the high contents of flavonoid and phenolic ingredients.

The protective effect of crawfish chitosan on the reproductive performance of obese male rats

Obesity is a global health issue that affects more than one-third of the population and is linked to several chronic consequences, including reproductive abnormalities. Chitosan is gaining popularity as a natural anti-obesity agent in various medical applications. As a result, this study aimed to evaluate the protective effect of crawfish chitosan on the reproductive capacity of male rats fed a high-fat diet. The crystallinity of chitosan particles was determined by X-ray diffraction (XRD). Twenty-one male Wistar rats were divided into three groups (n = 7/group); group I (control) was fed a standard pellet diet and water; group II, a high-fat diet (untreated), received 0.5 ml of 1% glacial acetic acid; and group III, a high-fat diet treated with 0.5 ml of 30 mg/kg/day of chitosan dissolved in 1% glacial acetic acid via oral gavage for 28 days. Many parameters were determined in this study, including sperm characteristics, hormonal profiles LH, FSH, and testosterone, as well as liver and kidney functions, testicular oxidative stress, and histological alterations. Results revealed that chitosan reduced body weight, enhanced sperm count and viability, and boosted reproductive hormone levels. It also increased antioxidant activity and improved kidney and liver functions compared to the HFD group. Histopathological observations of treated rats showed a normal appearance of seminiferous tubules with regular structure, displaying entire stages of spermatogenesis and presence of spermatids in the lumen. Conclusively, crawfish chitosan improved testicular dysfunction in HFD-fed rats by reducing oxidative stress.

Female and male obese Zucker rats display differential inflammatory mediator and long non-coding RNA profiles

AimsThe goal of this study was to identify mediators in peri-lymphatic adipose tissue (PLAT) that are altered in obese versus lean Zucker rats, with focus on potential sex differences Main methodsMesenteric PLAT was analyzed with protein and lncRNA arrays. Additional RT-PCR confirmation was performed with epididymal/ovarian fat. Key findingsMCP-1, TCK-1, Galectin-1, Galectin-3, and neuropilin-1 were elevated in PLAT from obese rats of both sexes. However, 11 additional proteins were elevated only in obese males while 24 different proteins were elevated in obese females. Profiling of lncRNAs revealed lean males have elevated levels of NEAT1, MALAT1 and GAS5 compared to lean females. NEAT1, MALAT1, and GAS5 were significantly reduced with obesity in males but not in females. Another lncRNA, HOTAIR, was higher in lean females compared to males, and its levels in females were reduced with obesity. Obese rats of both sexes had similar histologic findings of mesenteric macrophage crown-like structures and hepatocyte fat accumulation. SignificanceWhile obese male and female Zucker rats both have increased inflammation, they have distinct signals. Future studies of the proteome and lncRNA landscape of obese males vs. females in various animal models and in human subjects are warranted to better guide development of therapeutics for obesity-induced inflammation.

Sleeve Gastrectomy Provides Cardioprotection from Oxidative Stress In Vitro Due to Reduction of Circulating Myeloperoxidase.

Bariatric surgery, including sleeve gastrectomy (SG), improves systolic and diastolic function, which is independent of weight loss in rodent models. The cause of weight loss-independent improvements in cardiac function are unknown but may originate from the gastrointestinal tract. In this study, we investigated whether a circulating blood factor is a mechanism for acute cardioprotection after SG by testing the utility of rodent SG plasma to reduce metabolic stress in vitro. For the initial experiment, obese male Zucker rats underwent SG, ad lib sham, or pair-fed sham surgeries (n = six SG, n = eight SH, n = eight PF). For all other studies, a second group of Zucker rats underwent SG or ad lib sham surgeries (n = eight SH, n = six SG). Six weeks following surgery, plasma was collected from each group, both in the fasting and post-prandial (pp) state. This plasma was then pooled per surgical group and nutrient state and tested in multiple in vitro cell culture and extra-cellular assays to determine the effect of SG on myotubular metabolic stress compared to the sham surgeries. Post-prandial SG plasma (ppSG), but not fasting SG, pp, or fasting sham plasma, reduced the metabolic stress of the H9c2 cells as measured by lactate dehydrogenase (LDH) release (p < 0.01). Unlike SG, weight reduction through pair-feeding did not prevent H9c2 metabolic stress. The PpSG plasma had the slowest rate of extracellular hydrogen peroxide consumption and peroxidatic activity compared to the pp sham, fasting SG, and fasting sham groups. Redox testing of plasma with aminiobenzoic acid hydrazide and edaravone suggested a pattern supporting myeloperoxidase (MPO), or other peroxidases, as the primary component responsible for reduced metabolic stress with ppSG plasma. The PpSG plasma contained 35% less circulating MPO protein as compared to the pp sham and fasting SG plasma. The plasma from an MPO global knockout rat also prevented metabolic stress of the H9c2 cells, compared to the significant increase in LDH release from the plasma of the WT controls (p < 0.01). The MPO global knockout plasma also had a rate of extracellular hydrogen peroxide consumption and peroxidatic activity comparable to the ppSG plasma. These studies suggest that one of the weight loss-independent mechanisms by which SG improves myocellular function could be a reduced pro-oxidative environment due to lower circulating levels of MPO. It appears that the gastrointestinal tract is of critical importance to these findings, as the MPO levels were only lowered after enteral, nutrient stimulation in the SG rats. If this surgical effect is confirmed in humans, SG may be a unique surgical treatment for multiple diseases with a pathogenesis of inflammation and oxidative damage, including obesity-associated heart failure with preserved ejection fraction.

Finasteride effectively attenuates the impairments of left ventricular function and cardiac sympathovagal balance in both aging and obese male rats via reducing systemic oxidative stress

Abstract Background Cardiovascular diseases are commonly found in the elderly and obese population manifested by left ventricular (LV) dysfunction and impaired cardiac sympathovagal balance. Finasteride (FIN), a 5-alpha reductase inhibitor (5-ARI), is a universal prescription for patients with benign prostatic hyperplasia (BPH). Since BPH is commonly found in obesity and aging, it is essential to investigate whether FIN could have an impact on the LV function and cardiac sympathovagal balance in either elderly or obese conditions. Purpose We tested the hypothesis that impaired LV function and cardiac sympathovagal balance are observed in aging and obese conditions, and FIN improves these parameters through a reduction of systemic oxidative stress in both aging and obese male rats. Methods Twenty-four male Wistar rats (aged 8 weeks old) were randomly divided into 3 groups (n=8/group) to receive one of the followings: 1) normal diet (ND) feeding, 2) ND feeding with D-galactose injection (150 mg/kg/day, subcutaneous injection, 18 weeks) for creating an aging model, and 3) HFD feeding for 18 weeks for creating an obesity model. At week 13, rats in each group were divided into 2 subgroups (n=4/subgroup) and received either a vehicle (drinking water) or FIN (5 mg/kg/day) via oral gavage. At the end of treatment, echocardiography was performed to assess LV function, and the heart rate variability (HRV) was determined to quantify cardiac sympathovagal balance. The blood was collected, and serum was used to determine serum malondialdehyde (MDA) levels as a marker of systemic oxidative stress. Results At week 13, D-galactose injection successfully induced aging as indicated by increasing cardiac p53 protein expression. HFD also caused obesity in those rats as indicated by increased body weight and visceral fat weight. LV dysfunction (as indicated by reduced %LVEF and %LVFS) and cardiac sympathovalgal imbalance (as indicated by an increased LF/HF ratio) were observed in both models (Figure 1A-C). This functional impairment was associated with an increased MDA levels (Figure 1D). Treatment with FIN successfully reduced cardiac sympathovagal imbalance in both models (Figure 1C); however, an improvement of LV function was found only in aging rats-treated with FIN (Figure 1A, B). Consistent with a reduction of cardiac sympathovagal imbalance, FIN decreased systemic oxidative stress in both models (Figure 1D). Conclusions FIN effectively improved cardiac sympathovagal balance in rats under both aging and obese conditions. However, FIN reduced LV dysfunction only in aging rats. Interestingly, FIN did not affect these cardiac parameters in normal healthy rats. These findings suggest the cardioprotective potential of FIN in both aging and obese populations.

Exercise therapy against platelet levels in obesity

The purpose of this study was to determine the effect of Moderate Intensity Training (MIT) and High Intensity Interval Training (HIIT) on the number of platelets used as a treatment option for obesity. Materials and methods. This research is a true experimental laboratory study with a post test only control group design. Using 21 obese male Wistar rats with a distribution of 7 Wistar HIIT groups, 7 Wistar MIT, and 7 control Wistar groups. The exercise intervention consisted of HIIT intensity (90-100% of baseline ability), MIT intensity (60-80% of baseline ability), and control without training for six weeks. A special mouse treadmill is used for exercise. Platelet measurement by enzyme-linked immunosorbent assay (ELISA). Hematology tests are used to determine platelets. Data analysis used the Anova test. Results. There was a significant difference in platelets between the control, MIT and HIIT groups (p = 0.015). The mean value of platelets in MIT and HIIT was higher than the control group. HIIT vs Control there was no significant difference (p = 0.816) and MIT vs Control there was a significant difference (p = 0.017). Likewise HIIT vs MIT there is no significant difference (P = 0.058). Conclusion. Exercise with HIIT and MIT for 6 weeks can be used as an alternative to overcome obesity because it can reduce weight in obesity and is accompanied by an increase in platelets.

Effect of Cinnamon Hydro Alcoholic Extract on Ucp3 Expression in Adipose Tissue of High Fat Dietary Obese Male Wistar Rats

UCPs are the mitochondrial inner membrane proteins, which their primary role in the mitochondria is to guide hydrogen ions into the matrix.

Diet-induced animal model anti-obesity, phytochemical profiling, and in silico analysis of culinary plant gokhru (Pedalium murex L.) mucilage

Plant-based diets (PBDs) are renowned for managing and developing bioactive chemical inhibitors to combat obesity, a well-known global public health concern. There are currently no published research studies examining the effects of food plant mucilage dietary supplements on animal models of obesity induced by high-fat diets (HFD). The present research investigated the anti-obesity properties of the culinary plant Pedalium murex L. mucilage (PMM) in obese albino male rats models fed HFD. PMM's HR-LCMS phytochemical profiling and in silico evaluation of anti-obesity and drug-likeness using Schrodinger’s Glide, QikProp, and GROMACS modules were also investigated. In vivo, anti-obesity model animal rat’s daily dietary intake, common blood biochemical parameters, and histological examination of the liver and kidney tissues for the development of macrovesicular and microvesicular steatosis were all performed. Among the 46 Phytochemicals profiled, 7(14)-Bisabolene-2, 3, 10,11tetrol, Moschamine, and N-Feruloyltyramine show prominent anti-obesity activity and drug-like characteristics in silico. Rats given PMM showed significantly lower serum levels of total cholesterol (TC), low-density lipoprotein (LDL), and triglycerides (TGs), increased levels of high-density lipoprotein (HDL), as well as macro-and microvesicular steatosis, lobular inflammation of the liver and kidney tissues. This suggests that PMM is an effective natural anti-obesity therapeutic ingredient or dietary supplement with a high concentration of anti-obesity phytochemicals that mainly satisfies the needs for such natural anti-obesity medicine or a supplement. Communicated by Ramaswamy H. Sarma

Hyperbaric oxygen therapy exerts anti-osteoporotic effects in obese and lean D-galactose-induced aged rats.

Obesity accelerates the aging processes, resulting in an aggravation of aging-induced osteoporosis. We investigated the anti-osteoporotic effect of hyperbaric oxygen therapy (HBOT) in obese- and lean-aged rats through measurement of cellular senescence, hypoxia, inflammation, antioxidants, and bone microarchitecture. Obese and lean male Wistar rats were injected with 150 mg/kg/day of D-galactose for 8 weeks to induce aging. Then, all rats were randomly given either sham or HBOT for 14 days. Metabolic parameters were determined. Expression by bone mRNA for cellular senescence, hypoxia, inflammation, antioxidative capacity, and bone remodeling were examined. Micro-computed tomography and atomic absorption spectroscopy were performed to evaluate bone microarchitecture and bone mineral profiles, respectively. We found that HBOT restored the alterations in the mRNA expression level of p16, p21, HIF-1α, TNF-α, IL-6, RANKL, RANK, NFATc1, DC-STAMP, Osx, ALP, and Col1a1 in the bone in obese-and lean- aging rats. In obese-aging rats, HBOT increased the level of expression of Sirt1 and CuZnSOD mRNA and diminished the expression level of HIF-2α and ctsk mRNA to the same levels as the control group. However, HBOT failed to alter catalase and OCN mRNA expression in obese-aged rats. HBOT partially improved the bone microarchitecture in obese-aged rats, but completely restored it in lean-aged rats. Interestingly, HBOT protected against obesity-induced demineralization in obese-aged rats. In summary, HBOT exerts an anti-osteoporotic effect in lean-aged rats and prevents some, but not all the negative effects of obese-aged conditions on bone health. Therefore, HBOT is considered as a potential therapy for aging-induced osteoporosis, regardless of obese status.

Impacts of an 8-week regimen of aged garlic extract and aerobic exercise on the levels of Fetuin-A and inflammatory markers in the liver and visceral fat tissue of obese male rats

Obesity-induced chronic low-grade systemic inflammation is linked to the development of numerous diseases. Fetuin-A is known to affect inflammation and insulin resistance in obesity conditions. Free fatty acid (FFA)-induced proinflammatory cytokine expression in adipocytes occurs only in the presence of both Fetuin-A and toll-like receptor 4 (TLR4) and removing either of them prevented FFA-induced insulin resistance. Aged garlic extract (AGE) and exercise training have anti-inflammatory effects; however, the impact of AGE on Fetuin-A is unknown. We examined the effects of AGE with or without aerobic training (AT) on Fetuin-A and inflammatory markers. Forty healthy male Sprague Dawley rats were randomly assigned to normal diet (ND) (n=8) or high-fat diet (HFD) groups (n=32) and fed for 9 weeks. After 9 weeks ND group continued normal diet, and the HFD group was randomly assigned to the HFD, HFD+AGE (600mg/kg, once daily), HFD+AT (5 days/week), and HFD+AGE+AT groups that were continued for 8 weeks (n=8). The significance of differences among groups was assessed using one-way analysis of variance followed by the post-hoc Tukey test. Statistically significant differences were considered for p<0.05. AGE, AT, and AGE+AT significantly decreased body weight, plasma Fetuin-A, HOMA-IR, mRNA and protein levels of Fetuin-A and NFƙB in the liver and mRNA and Protein levels of Fetuin-A, TLR4 and NFƙB in visceral adipose tissue (VAT) compared to HFD. However, only AGE+AT significantly decreased TLR4 protein levels in the liver. Although AT and AGE reduce Fetuin-A and inflammatory markers, a combination of the two may be more effective at lowering inflammation.

Effects of Indonesian Shortfin Eel (Anguilla bicolor) By-Product Oil Supplementation on HOMA-IR and Lipid Profile in Obese Male Wistar Rats.

The prevalence of people being overweight and obese has increased globally over the past decades. The use of omega-3 fatty acids-a compound usually primarily found in fish oil-has been known to improve the metabolic profile of obese patients. As the demand for eels increases, the number of waste products from the eels increases and creates environmental problems. This study was conducted to investigate the effect of a newly discovered Indonesian Shortfin eel by-product oil supplementation on the Homeostasis Model Assessment-Estimated Insulin Resistance (HOMA-IR) and lipid profiles of obese male (Lee index ≥ 0.3) Wistar rats (Rattus norvegicus). The oil was extracted from waste products (heads). Fifteen obese rats were divided into three groups and were administered NaCl (C), commercial fish oil (CO), and Indonesian shortfin eel by-product oil (EO). All groups had statistically significant differences in total cholesterol, LDL, and triglyceride levels (p < 0.05). The CO and EO group showed a significant decrease in total cholesterol, LDL, and triglyceride after treatment. However, no significant difference was found in HDL levels and HOMA-IR. The supplementation of Indonesian shortfin eel by-product oil significantly improved lipid profile while effectively mitigating environmental challenges.

Oleaster oil (Olea europaea sylvestris) effects on the efficiency of the reproductive system of diet-induced obese male Wistar rats

Abstract Objectives Obesity is the result of oxidative stress (OS), which appears to be linked to male infertility. Oleaster oil has multiple therapeutic virtues due to its richness in natural bioactive compounds. This study aimed to evaluate the effect of Algerian oleaster oil on the reproductive system effectiveness of diet-induced obese male Wistar rats. Methods The oil was extracted with an oleodoseur from the oleaster fruits. Rats were fed for 28 weeks two diets: a normal diet (NC group, n=8) and a high-fat, high-sucrose diet (HFHS group, n=32). The obese rats in the HFHS group were then split into three groups at random: the HFHS group, which continued to receive the HFHS diet; the HFHS L-OO group; and the HFHS H-OO group, which received for 6 weeks, respectively, in combination with the HFHS diet, oleaster oil at 1.5 and 3 mL/100 g body weight (BW). Then, the animals were sacrificed. Semen and testes were removed for semen analysis, OS, and histopathological evaluation. Results The oleaster oil diet induces an improvement in sperm count and viability and a decrease in the percentage of fragmented sperm DNA compared to the group fed the HFHS diet, preserving the testes against OS with a highly significant decrease in testicular MDA. This beneficial effect of oleaster oil on the reproductive efficiency of rats fed the HFHS diet was dose-dependent. Conclusions The results showed that the oil decreased body weight, prevented OS and improved male reproductive indicators in HFHS-fed animals. The potential positive effects of oleaster oil on fertility biomarkers may be attributed to its ability to mitigate OS.

Potential anti-obesity effects of two-graded doses of Iraqi Hibiscus tiliaceus leaves extract, alone and in combination with orlistat, on high-fat diet-induced obesity in male rats.

Obesity is a world health concern and a serious risk factor for several chronic diseases. Hibiscus tiliaceus is a plant with reported anti-obesity properties. However, the preclinical anti-obesity effect of ethanolic extract of Iraqi Hibiscus tiliaceus has not been studied yet. This study aimed to evaluate the preclinical anti-obesity properties of Iraqi Hibiscus tiliaceus extract, alone or in combination with orlistat, on high-fat diet-induced obesity in male rats. Male rats were divided into five groups: control, induction, ethanolic extract of Iraqi Hibiscus tiliaceus (250 mg/kg and 500 mg/kg), orlistat (Xenical) alone (10 mg/kg), and a combination of the extract (250 mg/kg) with Xenical. The rats were fed a high-fat diet to induce obesity, and treatments were given orally for 8 weeks. Body weight, food intake, serum lipid profile, and liver enzymes were measured. Administration of ethanolic extract of Iraqi Hibiscus tiliaceus (250 mg/kg and 500 mg/kg), Xenical alone (10 mg/kg), and combination with the extract (250 mg/kg) for 8 weeks significantly reduced body weight, food intake, serum triglycerides, total cholesterol, low-density lipoprotein cholesterol, and liver enzymes (aspartate transaminase and alanine transaminase) when compared to the induction group. The ethanolic extract of Iraqi Hibiscus tiliaceus showed anti-obesity effects and could be a potential therapeutic agent in managing obesity. However, further studies are needed to evaluate its clinical efficacy and safety.

Unravelling the anti-inflammatory and antioxidant effects of standardized green and black caffeinated coffee, tea, and their mixtures in an obese male rat model: Insights from biochemical, metabolomic, and histopathological analyses.

Obesity is one of the major metabolic syndrome risk factors upon which altered metabolic pathways follow. This study aimed to discern altered metabolic pathways associated with obesity and to pinpoint metabolite biomarkers in serum of obese rats fed on high fructose diet using metabolomics. Further, the effect of standardized green versus black caffeinated aqueous extracts (tea and coffee) in controlling obesity and its comorbidities through monitoring relevant serum biomarkers viz. Leptin, adiponectin, spexin, malondialdehyde, total antioxidant capacity. Liver tissue oxidative stress (catalase, super oxide dismutase and glutathione) and inflammation (IL-1β and IL-6) markers were assessed for green coffee and its mixture with green tea. Results revealed improvement of all parameters upon treatments with more prominence for those treated with green caffeinated extract (coffee and tea) especially in mixture. Upon comparing with obese rat group, the green mixture of coffee and tea exhibited anti-hyperlipidemic action through lowering serum triglycerides by 35.0% and elevating high density lipoprotein by 71.0%. Black tea was likewise effective in lowering serum cholesterol and low density lipoprotein by 28.0 and 50.6%, respectively. GC-MS- based metabolomics of rat serum led to the identification of 34 metabolites with obese rat serum enriched in fatty acids (oleamide).

Interaction between high-intensity interval training and high-protein diet on gut microbiota composition and body weight in obese male rats.

Diet and exercise are two critical factors that regulate gut microbiota, affecting weight management. The present study investigated the effect of 10 weeks of high-intensity interval training (HIIT) and a high-protein diet (HPD) on gut microbiota composition and body weight changes in obese male Wistar rats. Forty obese rats were randomly divided into five groups, including HPD, HIIT + HPD, HIIT + high-fat diet (HFD) (continuing HFD during intervention), obese control 1 (continuing HFD during intervention), obese control 2 (cutting off HFD at the beginning of the intervention and continuing standard diet), and eight non-obese Wistar rats as a non-obese control (NOC) group (standard diet). Microbial community composition and diversity analysis by sequencing 16S rRNA genes derived from the fecal samples, body weight, and Lee index were assessed. The body weight and Lee index in the NOC, HIIT + HFD, HPD, and HIIT + HPD groups were significantly lower than that in the OC1 and OC2 groups along with the lower body weight and Lee index in the HPD and HIIT + HPD groups compared with the HIIT + HFD group. Also, HFD consumption and switching from HFD to a standard diet or HPD increased gut microbiota dysbiosis. Furthermore, HIIT along with HFD increased the adverse effects of HFD on gut microbiota, while the HIIT + HPD increased microbial richness, improved gut microbiota dysbiosis, and changed rats' phenotype to lean. It appears that HFD discontinuation without doing HIIT does not improve gut microbiota dysbiosis. Also, the HIIT + HFD, HPD, and HIIT + HPD slow down HFD-induced weight gain, but HIIT + HPD is a more reliable strategy for weight management due to its beneficial effects on gut microbiota composition.

Ramadan fasting model exerts hepatoprotective, anti-obesity, and anti-hyperlipidemic effects in an experimentally-induced nonalcoholic fatty liver in rats.

The epidemic of nonalcoholic fatty liver disease (NAFLD) and its metabolic effects present a serious public health concern. We hypothesized that the Ramadan fasting model (RFM), which involves fasting from dawn to dusk for a month, could provide potential therapeutic benefits and mitigate NAFLD. Accordingly, we aimed to validate this hypothesis using obese male rats. Rats were split into two groups (n = 24 per group), and they were given either a standard (S) or high-fat diet (HFD) for 12 weeks. During the last four weeks of the study period, both S- and HFD-fed rats were subdivided into eight groups to assess the effect of RFM with/without training (T) or glucose administration (G) on the lipid profile, liver enzymes, and liver structure (n = 6/group). The HFD+RFM group exhibited a significantly lower final body weight than that in the HFDC group. Serum cholesterol, low-density lipoprotein, and triglyceride levels were significantly lower in the HFD+RFM, HFD+RFM+T, and HFD+RFM+G groups than those in the HFDC group. Compared with the HFDC group, all groups had improved serum high-density lipoprotein levels. Furthermore, HFD groups subjected to RFM had reduced serum levels of aspartate transaminase and alanine transaminase compared with those of the HFD-fed group. Moreover, the liver histology improved in rats subjected to RFM compared with that of HFD-fed rats, which exhibited macro- and micro-fat droplet accumulation. RFM can induce positive metabolic changes and improve alterations associated with NAFLD, including weight gain, lipid profile, liver enzymes, and hepatic steatosis.

Ameliorative effects of Orlistat and metformin either alone or in combination on liver functions, structure, immunoreactivity and antioxidant enzymes in experimentally induced obesity in male rats

BackgroundPrevalence of obesity is increasing worldwide. Obesity is associated with incidences of metabolic disorders and cardiovascular diseases and the risk of having it rose sharply during the COVID-19 pandemic. Obesity is associated with oxidative stress, inflammatory markers and hepatic disorders and has become one of the silent killer diseases affecting global health. MethodsThis study examined the effects of obesity on liver functions (ALT, AST and LDH), lipid profile (TG, TC, HDL-c, LDL-c and vLDL-c), tumour necrosis factor alpha (TNF-α), inflammatory marker, C-reactive protein (CRP), leptin hormone and antioxidant enzymes (CAT, SOD and GPx) and lipid peroxidation marker (MDA) in liver homogenates besides histological structure of the liver tissues and assessment of DNA damage. Fifty male Wistar rats were used and they were divided into five treatment groups: I-Control group, II-high-fat diet (HFD) treated group (Obesity) group, III-HFD plus Orlistat (ORL), IV-HFD plus metformin (Met) and V- HFD plus ORL plus Met. ResultsExperimentally-induced obesity caused a significant increase in liver enzymes including lipid markers (triglycerides and total cholesterol), inflammatory markers, tumour markers and lipid peroxidation markers and a concurrent decline in antioxidant enzymes and damage of liver main structures characterised by presence of congestion and accumulation of mononuclear inflammatory cells in blood sinusoids. In contrast, groups treated with either ORL or Met or both group, we recorded restoration of normal hepatic structures and a decline in DNA damage, liver enzymes and antioxidant levels. The best restoration and amelioration were observed in the group treated with a combination of ORL and Met. ConclusionOur findings indicated the synergistic effect of ORL and Met in ameliorating hepatic functions and lipid profile, alleviating inflammation, genotoxicity and side effects of experimentally-induced obesity.

The effect of aerobic training and hydroalcoholic extract of dill on skeletal muscle inflammation in a high-fat diet-induced obesity rat model

Abstract Aerobic training (AT) and herbal medicine interventions are effective in reducing chronic inflammation and achieving weight loss. The present study aimed to investigate the effect of 10 weeks of AT and hydroalcoholic extract of dill (HED) on tumour necrosis factor-alpha (TNF-α), interleukin-4 (IL-4), and peroxisome proliferator-activated receptor gamma (PPARγ) concentrations in gastrocnemius muscle and Lee index of obese male rats. Thirty-two obese male Wistar rats were randomly divided into AT (70-80% of maximal oxygen uptake, 5 times/week), HED (300 mg/kg body weight, 3 times/week), AT+HED, and obese control (Ctr), and eight non-obese rats were included in the non-obese control group (NCtr). Lee index was measured before and after 10 weeks of interventions. Also, rats were sacrificed 48 hs after the last intervention session and gastrocnemius muscle was removed to measure protein concentrations of TNF-α, IL-4, and PPARγ. When compared with the pre-intervention period, the Lee index decreased in the AT and AT+HED groups and increased in the NCtr group at the post-intervention period. Also, there was no significant difference between non-obese and obese rats in the concentrations of TNF-α and IL-4, but the AT+HED group showed a higher concentration of TNF-α than the AT group. Furthermore, the expression of PPARγ protein in the HED group was higher than in the Ctr and AT groups. Although we observed the beneficial effects of AT and its combination with HED in reducing the Lee index, we found that the administration of HED compared with AT can provide better protection against some metabolic complications in the skeletal muscles of obese rats caused by a high-fat diet. Lastly, it seems that the AT combined with HED interferes with possible anti-inflammatory effects of AT or HED intervention alone.

Effect of HIIT and MIT on TNF-α levels and blood profile for obesity therapy

Study purpose. Discusses the outcomes of Moderate Intensity Training (MIT) and High Intensity Interval Training (HIIT) on Tumor Necrosis Factor-alpha (TNF-α) and blood profiles to be used as a treatment option for obesity. Material and Methods. This research is a true experimental laboratory with a post-test-only control group design. Using 39 obese male Wistar rats with the distribution of 13 Wistar HIIT groups, 13 Wistar MIT, and 13 Wistar control. The exercise intervention consists of HIIT intensity (90–100% of baseline ability), MIT intensity (60-80% of baseline ability), and control without training for six weeks. A specialized rat treadmill was used for the exercises. Measuring of TNF-α levels with an enzyme-linked immunosorbent assay (ELISA). Hematology test used to determine levels of eritrosit, leukosit, trombosit. Data analysis used the Anova test. Result. TNF-α levels in MIT and HIIT were significantly higher than control levels, as indicated by P values of 0.003 (HIIT vs Control) and 0.001 (MIT vs Control). There weren’t any big differences. in the blood tests for erythrocytes, leukocytes, and platelets between groups. At body weight, HIIT is lower than the control P = 0.000, and MIT is also lower than the control P = 0.002. Conclusion. Exercise with HIIT and MIT for 6 weeks can be used as an alternative to overcome obesity because it can reduce weight obesity, but not accompanied by a decrease in TNF-α and erythrocytes, leukocytes, and platelets.

400-P: Spatial Metabolomics Analysis by MSI-DeepPath Identifies Key Pathways in ZDF Diabetic Kidney Disease Model

Background: The Zucker Diabetic Fatty (ZDF) rat is a popular model of type 2 diabetes as it develops pathologic changes in the kidney similar to human diabetic nephropathy. To identify metabolic pathways linked to pathologic features MALDI mass spectrometry imaging (MSI) can be a powerful platform. However, quantification of metabolites from MALDI-MSI is very challenging. Our MSI-DeepPath computational platform enables spatial quantitation of metabolites from any tissue section size. Methods: Control and obese ZDF male rats (age 6mo, n=5/group) were studied. Spatial metabolomics analysis of kidney tissue sections was performed using MALDI-MSI at 20 µm resolution. Metabolites were detected at mass accuracy &amp;lt;2 ppm using Q-Exactive orbitrap MS followed by annotations using METASPACE. SygnaMap’s MSI-DeepPath computational platform was used to quantify the annotated metabolites. Results: Of 400 metabolites annotated at m/z range 70-500 Da the top features were selected using t-test, p value and fold change analysis. The top 20 biomarkers that separated ZDF from controls included glucose, serine, histidine, and glutamate. The most significantly upregulated metabolite was tyrosinamide (8.2-fold, p=8.02 x 10-9 ). The most significant downregulated metabolite was L-threonine (0.3-fold, p=2.03 x 10-9). Pathway analysis revealed that aminoacyl-tRNA biosynthesis, galactose, glyoxylate and dicarboxylate metabolic pathways can discriminate healthy from diabetic kidney samples. Conclusion: MSIDeepPath enables quantification of spatial metabolomics of tissue sections using MALDI-MSI data. This new tool can be applied across normal and diseased samples allowing for robust statistical analysis of spatial omics data. Using MSI-DeepPath on kidney sections from the ZDF rat we identified regulation of metabolites linked to key pathways of diabetic kidney disease. Disclosure L.Hejazi: None. S.Sharma: None. A.Ruiz: None. G.Zhang: None. F.C.Tucci: None. K.Sharma: Advisory Panel; Reata Pharmaceuticals, Inc., Otsuka America Pharmaceutical, Inc. Funding National Institutes of Health (1R43DK130732-01A1)