Rat Model Of Diet-induced Obesity Research Articles

Investigation of calonysterone and 20-hydroxyecdysone effects in high-fat, high-sugar diet-induced obesity rat model

Investigation of calonysterone and 20-hydroxyecdysone effects in high-fat, high-sugar diet-induced obesity rat model

Discovery of 1,4-Disubstituted Cyclohexene Analogues as Selective GPR119 Agonists for the Treatment of Type 2 Diabetes.

GPR119 has emerged as a promising target for treating type 2 diabetes and associated obesity, as its stimulation induces the secretion of glucagon-like peptide-1 and glucose-dependent insulinotropic peptide in the intestinal tract as well as the glucose-dependent release of insulin in pancreatic β-cells. We describe the design and synthesis of novel GPR119 agonists containing a 1,4-disubstituted cyclohexene scaffold. Compound 21b displayed nanomolar potency (EC50 = 3.8 nM) for hGPR119 activation and demonstrated a hypoglycemic efficacy of 17.0% in an oral glucose tolerance test. The hypoglycemic effect of compound 21b, compared to sitagliptin, a DPP-4 inhibitor, showed the relatively higher efficacy in both FATZO and db/db mice. Additionally, compound 21b exhibited a significant reduction in body weight in a female diet-induced obese rat model, comparable to that of metformin. Furthermore, in vivo pharmacokinetic experiments revealed that compound 21b is a potential candidate for the treatment of type 2 diabetes and obesity.

Brown Rice: A Promising Therapeutic Strategy for Reducing Inflammatory Markers in the Adipose Tissue of Diet-Induced Obesity Rat Model

Obesity is closely linked to adipose tissue inflammation, where macrophages play a crucial role. One approach to enhance the issue of obesity is by implementing nutritional intervention. This study designed to investigate the impact of administering brown rice and gamma oryzanol (ORZ) on reducing adipose tissue expansion and inflammation in a rat model of diet-induced obesity. The study involved male Sprague-Dawley rats of the Rattus novergicus strain. The negative control group received AIN93M as the standard diet, while the remaining were induced to become obese by high-fat, high fructose (HFHFr) diet. Then, we divided them into 4 treatment groups: mix HFHFr diet with brown rice; white rice; white rice + ORZ; and ORZ only. Treatment was given for 12 weeks. Histological examination was used to measure both the size and number of adipocytes. Immunohistochemical staining was done to evaluate the infiltration of macrophages into adipose tissue, while immunofluorescence labelling was utilized to examine the expression of macrophages M1 and M2. The addition of brown rice and ORZ appears to improve adipocyte expansion. The brown rice group showed the least amount of M1 macrophages, while the negative control group showed the highest amount of M2 macrophages, leading to much lower M1/M2 ratios compared to the other groups. No differences were found in the study of variables in either visceral or subcutaneous adipose tissue. Brown rice and ORZ can potentially improve adipose tissue expansion and suppress the expression of pro-inflammatory macrophages.

Semaglutide normalizes increased cardiomyocyte calcium transients in a rat model of high fat diet-induced obesity.

Obesity increases the risk of heart failure with preserved (HFpEF), but not reduced ejection fraction (HFrEF). The glucagon-like peptide-1 receptor agonist (GLP-1-RA) semaglutide improves outcome of patients with obesity with or without HFpEF, while GLP-1-RAs were associated with adverse outcome in patients with HFrEF. Here, we investigate the effect of in vivo treatment with semaglutide on excitation-contraction coupling in a rat model of obesity. Rats received high-fat/high-fructose diet for 8weeks and were then randomized to semaglutide (HFD/Sema) or vehicle (HFD/Veh) for another 8weeks, during which they could choose between HFD and a low-fat/high-fructose diet (LFD). Control rats received either standard chow (CON), HFD or LFD only, without treatment. After 16weeks, sarcomere shortening and cytosolic Ca2+ concentrations ([Ca2+]c) were determined in isolated cardiomyocytes. Compared with CON, HFD/Veh increased the amplitude of [Ca2+]c transients and systolic sarcomere shortening in absence or presence of β-adrenergic stimulation, which was reversed by HFD/Sema. Caffeine-induced sarcoplasmic reticulum (SR) Ca2+ release and L-type Ca2+ channel (LTCC) currents were reduced by HFD/Sema versus HFD/Veh, while SR Ca2+ ATPase activity remained unaffected. Compared with HFD, LFD increased [Ca2+]c transients and sarcomere shortening further despite similar effects on body weight. While HFD increased cardiomyocyte [Ca2+]c transients and systolic sarcomere shortening, semaglutide normalized these alterations, mediated by reduced SR Ca2+ load and LTCC currents. Because increased LTCC currents were previously traced to cardiac hypertrophy, these effects may explain why GLP-1-RAs provide benefits for patients with obesity with or without HFpEF, but rather adverse outcome in HFrEF.

Aerobic Exercise Improved Diacylglycerol/Protein Kinase C and Phosphatidylinositol 4,5-Biphosphate Pathway in Cardiac Tissue of Obese Rats

Background: Obesity, characterized by abnormal accumulation or excess lipids, is a major cause of increased incidence of cardiovascular diseases. Objectives: The purpose of this experiment is to investigate the effect of aerobic exercise on the expression of sn-1,2-diacylglycerol (DAG), Protein kinase C (PKC), and Phosphatidylinositol 4,5-biphosphate (PIP2) genes in experimental rat models of diet-induced obesity. Methods: Twenty-four Wistar rats were randomly divided into four groups: (1) control, (2) obesity, (3) exercise, and (4) obesity + exercise. At the end of the experiment, cardiac hypertrophy markers and real-time PCR were used to evaluate and compare the gene expression levels of DAG, PKC, and PIP2 in cardiac tissue across all groups. Results: A high-fat diet containing fructose significantly increased the gene expression levels of DAG, PKC, and PIP2 in the cardiac tissue of obese rats compared to the control group. However, 6 weeks of aerobic exercise led to a significant decrease in DAG and PKC gene expression compared to the obese rats. Although there was no significant change in PIP2 gene expression in the obesity + exercise group compared to obese rats. Conclusions: Based on the results of this study, it appears that aerobic exercise can modulate the expression of DAG and PKC genes, which play a critical role in cardiac remodeling.

Reoxygenation improves reduced hypothalamic leptin responsiveness induced by intermittent hypoxia in obese rats

To evaluate the effects of intermittent hypoxia-reoxygenation (IHR) on body weight, diet and water intake, circulating metabolites, and responses to central leptin injection in a rat model of diet-induced obesity (DIO). Rat models of DIO established by 12-week high-fat diet (HFD) feeding were randomized into normoxia group (n=15), intermittent hypoxia group (6% O2, 30 cycles/h, 8 h/day for 4 weeks; n=15), and IHR group (2 weeks of intermittent hypoxia followed by 2 weeks of reoxygenation; n=15). Body weight, diet and water intake of the rats were recorded, and circulating leptin, IL-6, and Ang-II levels were detected. After IHR treatment, the rats received intracerebroventricular injection of 4 μg leptin, and the hypothalamus and liver were taken 1 h later for detecting POMC, FRA-1 and FRA-2 expressions in the hypothalamus using immunohistochemistry, POMC, pSTAT3 and LepR expressions in the hypothalamus using Western blotting, and LepR mRNA expression in the hypothalamus and liver using RT-PCR. The rats in intermittent hypoxia group showed significantly increased weight gain, food intake and elevated systemic inflammatory cytokine levels. Intermittent hypoxia obviously inhibited the expression of POMC, lowered the expressions of FRA-1 and pSTAT3, reduced the responsiveness of the rats to exogenous leptin, and downregulated the mRNA and protein expression of LepR. Two weeks of reoxygenation treatment obviously reduced intermittent hypoxia-induced weight gain and metabolic disorder and improved leptin sensitivity of the rats. Prolonged intermittent hypoxia impairs hypothalamic leptin signaling by downregulating LepR expression to promote weight gain in obese rats, which can be improved by reoxygenation treatment.

Combination of Metformin and Epigallocatechin-3-Gallate Lowers Cortisol, 11β-Hydroxysteroid Dehydrogenase Type 1, and Blood Glucose Levels in Sprague Dawley Rats with Obesity and Diabetes.

The combined effects of metformin and epigallocatechin-3-gallate (EGCG) on cortisol, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), and blood glucose levels have not been investigated. This study evaluated the effectiveness of combining EGCG with metformin in regulating those levels in a rat model of diet-induced diabetes and obesity. Thirty diabetic and obese rats on a high-fat diet were treated daily for 28 days with EGCG (100 mg/kg of body weight/day), metformin (200 mg/kg of body weight/day), or both. Control groups comprised lean rats, untreated obese diabetic rats, and metformin-only-treated rats. Blood samples were collected to measure cortisol and fasting blood glucose (FBG) levels and liver tissue samples were examined for 11β-HSD1 levels. Rats receiving combination therapy had significantly reduced cortisol levels (from 36.70±15.13 to 31.25±7.10 ng/mL) compared with the untreated obese diabetic rats but not the rats receiving monotherapy. Rats receiving combination therapy and EGCG monotherapy had significantly lower 11β-HSD1 levels compared with the untreated obese diabetic rats (92.68±10.82 and 93.74±18.11 ng/L vs. 120.66±14.00 ng/L). Combination therapy and metformin monotherapy significantly reduced FBG levels (440.83±133.30 to 140.50±7.36 mg/dL and 480.67±86.32 to 214.17±102.78 mg/dL, respectively) by approximately 68.1% and 55.4% compared with rats receiving EGCG monotherapy and untreated obese diabetic rats. Combining EGCG with metformin exhibited synergistic effects compared with monotherapy for managing diabetes, leading to improved outcomes in reduction of baseline cortisol levels along with reduction in 11β-HSD1 and blood glucose levels.

Dahuang Huanglian Xiexin Decoction ameliorates obesity via modulating adipocyte differentiation and lipid degradation through inhibiting endoplasmic reticulum stress

Dahuang Huanglian Xiexin Decoction (DHXD) is the representative clinical formula for treating epigastric oppression. In this study, we aim to explore the effect of DHXD on obesity and attempt to investigate its potential mechanism. 3T3-L1 preadipocytes were differentiated and high-fat diet-induced obese rat model was established. DHXD was used for treatment and tunicamycin, the activator of endoplasmic reticulum (ER) stress, was adopted to investigate the related regulatory mechanism. Cell viability was evaluated using CCK-8 assay. Oil-Red O staining was performed to determine lipid accumulation. Glycerol production and Triglyceride content were measured using their commercial kits. Western blot was conducted to examine the expression of critical proteins. Results indicated that DHXD could greatly reduce intracellular lipid droplets and triglyceride in differentiated 3T3-L1 cells. Moreover, the elevated expression of mature adipocytes markers, PPARγ, aP2, during adipogenesis was decreased by DHXD treatment. In addition, DHXD aggravated the lipolysis in differentiated 3T3-L1 cells, as evidenced by the upregulated ATGL expression and the downregulated HSL expression. Besides, DHXD inhibited endoplasmic reticulum (ER) stress in 3T3-L1 cells. Further experiments indicated that the impacts of DHXD on adipocyte differentiation and lipid degradation were partly abolished by tunicamycin. Finally, DHXD alleviated lipid accumulation and ER stress in obese rats. In conclusion, DHXD ameliorates obesity via modulating adipocyte differentiation and lipid degradation through inhibiting ER stress.

HPP-1S attenuates oleic acid-induced steatosis in HepG2 cells and nonalcoholic fatty liver disease in a rat model of high-fat diet-induced obesity

HPP-1S is a new polysaccharide that was isolated and purified from the gonads of sea urchins in our laboratory. The aim of this study was to investigate the therapeutic effect of the polysaccharide HPP-1S on nonalcoholic fatty liver disease (NAFLD). The results showed that HPP-1S suppressed lipid accumulation in oleic acid (OA)-treated HepG2 cells. In vivo experiments shown that treatment with HPP-1S can reduce lipid accumulation and inhibit liver damage. Further mechanistic investigation indicated that HPP-1S treatment increased the phosphorylation of AMP-activated protein kinase (AMPK). Additionally, the expression of sterol regulatory element-binding protein-1 (SREBP1) and fatty acid synthase (FAS) decreased. After treatment with HPP-1S, the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and Sirtuin 1 (SIRT1) increased. These results reveal the promising role of HPP-1S in the prevention and treatment of NAFLD. These findings contribute to the development of new therapeutic strategies for the clinical treatment of NAFLD.

The Metabolic and Endocrine Effects of a 12-Week Allulose-Rich Diet

The global rise in type 2 diabetes (T2D) and obesity necessitates innovative dietary interventions. This study investigates the effects of allulose, a rare sugar shown to reduce blood glucose, in a rat model of diet-induced obesity and T2D. Over 12 weeks, we hypothesized that allulose supplementation would improve body weight, insulin sensitivity, and glycemic control. Our results showed that allulose mitigated the adverse effects of high-fat, high-sugar diets, including reduced body weight gain and improved insulin resistance. The allulose group exhibited lower food consumption and increased levels of glucagon-like peptide-1 (GLP-1), enhancing glucose regulation and appetite control. Additionally, allulose prevented liver triglyceride accumulation and promoted mitochondrial uncoupling in adipose tissue. These findings suggest that allulose supplementation can improve metabolic health markers, making it a promising dietary component for managing obesity and T2D. Further research is needed to explore the long-term benefits and mechanisms of allulose in metabolic disease prevention and management. This study supports the potential of allulose as a safe and effective intervention for improving metabolic health in the context of dietary excess.

Anti-obesity effect of seaweed algae (Ascophyllum nodosum) extracts in the 3T3-L1 cell line and a high-fat diet-induced obesity rat model

Obesity can be induced by the accumulation of adipose tissue via overconsumption of high-energy intake, and unbalanced synthesis of various hormones. Recently, seaweed algae have attracted researchers’ attention due to their health-beneficial effects, however, the antiobesity effects of Ascophyllum nososum are still controversial. We conducted two experiments with 3T3-L1 cell line and obese mouse model to elucidate the exact mechanism of seaweed algae extract (AE).In the in vivo study, dietary AE supplementation decreased body weight without affecting feed consumption. AE reduced the total mass, fat mass, and gonadal fat of the mice without changing the lean mass weight. Additionally, dietary AE addition could restore serum markers related to lipid metabolism (triglycerides and total cholesterol) as much as those of control mice.Furthermore, the in vitro study with 3T3-L1 cells suggested that AE treatment significantly suppressed adipogenesis by decreasing expression levels of lipogenesis-related genes and lipid-utilization genes with increasing the ratio of phosphorylated AMPK to AMPK and phosphorylated ACC to ACC.Collectively, Ascophyllum nodosum extract could restore obesity induced by a high-fat diet, which might be due to the decrease in lipogenesis with the increase in lipid utilization through the AMPK-ACC signaling pathway.

Potential Benefits of Ethanol extract of Anredera cordifolia for Antiobesity of High Fat diet-Induced Obesity in White Male Rat Wistar

تستمر الوفيات المرتبطة بالسمنة في الارتفاع ، لذلك من الضروري إنقاص الوزن لتجنب المضاعفات ، نريديرا كورديفوليا هو نوع من النباتات النضرة من الجنس، باسيللسيا يستخدم على نطاق واسع في طب الأعشاب لتقليل وزن الجسم. تهدف الدراسة الحالية إلى تقييم الفوائد المحتملة لمستخلص الإيثانول من نريديرا كورديفوليا لنماذج الفئران السمنة لتقليل الوزن الناجم عن نظام غذائي عالي الدهون. من خلال تجريب مع اختبارات ما بعد فقد تم تصميم مجموعة ضابطة مع نموذج سمنة 36 جرذًا ، مقسمة إلى مجموعتين: ثلاث مجموعات تحكم (K1 ، K2 ، K3) وثلاث مجموعات معالجة (K1 ، K3 ، K4) (P1 ، P2 ، P3) ، أعطيت جميع مجموعات تحتوي على نسبة عالية من الدهون باستثناء K1 نظام غذائي قياسي ، K2 بدون علاج ، و K3 مع أورليستات. تلقت مجموعة العلاج من مستخلص الإيثانول نريديرا كورديفوليا بجرعات مختلفة ، P1 50 مجم / كجم من وزن الجسم ، P2 100 مجم / كجم من وزن الجسم، و P3 150 مجم / كجم من وزن الجسم. بعد 4 أسابيع من العلاج، قُتلت جميع مجموعات الفئران ، وتم قياس مستويات ERK و PPARγ في الأنسجة الدهنية الحشوية في البطن باستخدام ELISA والكيمياء المناعية. يتم قياس وزن الجسم ومحيط البطن أثناء فحص القياسات، وقد لوحظ فقدان الوزن عند تناول مستخلص الإيثانول نريديرا كورديفوليا بجرعات 100 و 150 مجم / كجم من وزن الجسم، مع انخفاض مستويات ERK و PPAR . يستخدم مستخلص الإيثانول من نريديرا كورديفوليا كمضاد للسمنة. تقلل آلية فقدان الوزن هذه من عامل نسخ PPARγ وتقلل من مستويات ERK بحيث تقل عملية تكوين الدهون.

Attenuation of palmitic acid-induced lysyl oxidase overexpression in the ovary contributes to the improvement of ovulation in obesity by metformin

Abstract STUDY QUESTION Does palmitic acid (PA), the most common saturated free fatty acid (FFA) in individuals with obesity, contribute to anovulation through upregulation of the collagen-crosslinking enzyme lysyl oxidase (LOX) in the ovary? SUMMARY ANSWER Increased PA in individuals with obesity can cause LOX upregulation via the activation of hypoxia-inducible factor-1α (HIF-1α), resulting in abnormal collagen deposition in the ovary and anovulation, which can be ameliorated by metformin therapy. WHAT IS KNOWN ALREADY The underlying cause of anovulation in individuals with obesity is poorly defined, and accumulating evidence indicates that hormonal disturbance, insulin resistance, and inflammation may all play a role in the development of ovulation disorders in individuals with obesity. However, it remains to be determined whether PA plays a role in the regulation of LOX expression, thus disrupting ovarian extracellular matrix (ECM) remodelling in the ovary and resulting in impaired ovulation in individuals with obesity. STUDY DESIGN, SIZE, DURATION PA concentration and LOX protein abundance and activity in follicular fluid and ovarian tissue were compared between control (n = 21) subjects, patients with obesity with ovulation (n = 22), and patients with obesity with anovulation (n = 16). The effect of PA on LOX protein expression, and the underlying mechanism, was examined in primary human granulosa cells in vitro. The improvements in obesity conditions induced by LOX inhibition combined with metformin were investigated in a high-fat diet-induced obese rat model. PARTICIPANTS/MATERIALS, SETTING, METHODS The abundance of PA concentration and LOX activity was measured via a LOX activity assay and ELISA, respectively. The effect of PA on LOX protein expression was examined in the presence or absence of inhibitors of signalling molecules and siRNA-mediated knockdown of the putative transcription factor. Chromatin immunoprecipitation assays were subsequently conducted to further identify the responsible transcription factor. The role of metformin in the treatment of anovulation by LOX inhibition was investigated in a high-fat diet (HFD)-induced obese rat model. The numbers of retrieved total oocytes and metaphase II oocytes were recorded upon ovarian stimulation. Masson’s trichrome staining was used to measure the total collagen content, and immunohistochemical staining and western blotting were used to measure LOX, HIF-1α, and collagen I and IV in the ovary. MAIN RESULTS AND THE ROLE OF CHANCE Significantly increased FFA, LOX, and collagen abundance were observed in the ovaries of obese women with anovulation, compared to healthy controls or obese women with ovulation. In a HFD-induced obese rat model, metformin corrected the distortion of ovarian morphology by decreasing LOX and collagen protein abundance in the ovary and improving oestrous cyclicity and ovulation. PA increased LOX expression via the activation of HIF-1α in human granulosa cells, which was attenuated by metformin. LARGE SCALE DATA N/A. LIMITATIONS, REASONS FOR CAUTION Several other saturated and polyunsaturated FFAs, such as stearic acid and arachidonic acid, are also increased in the blood of individuals with obesity, and increased levels of other FFAs may also contribute to the development of anovulation in individuals with obesity, which needs to be further verified in the future. WIDER IMPLICATIONS OF THE FINDINGS Elevated PA in individuals with obesity can cause LOX dysregulation via activation of HIF-1α, resulting in abnormal collagen deposition in the ovary and anovulation. This dysregulation can be ameliorated by metformin therapy through its local effect on ECM remodelling in the ovary, which is independent of its systemic effect on insulin sensitivity and chronic inflammation. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the National Natural Science Foundation of China (grant numbers 82101730, 82130046, and 31900598) and Innovative Research Team of High-level local Universities in Shanghai (SHSMU-ZLCX20210201). All the authors declare no conflicts of interest in relation to this work.

Liver Oxidative Status, Serum Lipids Levels after Bariatric Surgery and High-Fat, High-Sugar Diet in Animal Model of Induced Obesity.

Nutritional status is a major determinant of hepatocyte injuries associated with changed metabolism and oxidative stress. This study aimed to determine the relations between oxidative stress, bariatric surgery, and a high-fat/high-sugar (HFS) diet in a diet-induced obesity rat model. Male rats were maintained on a control diet (CD) or high-fat/high-sugar diet (HFS) inducing obesity. After 8 weeks, the animals underwent SHAM (n = 14) or DJOS (n = 14) surgery and the diet was either changed or unchanged. Eight weeks after the surgeries, the activity of superoxide dismutase isoforms (total SOD, MnSOD, and CuZnSOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and lutathione S-transferase, as well as the thiol groups (-SH) concentration, total antioxidant capacity (TAC), total oxidative stress (TOS) levels, and malondialdehyde (MDA) concentration liver tissue were assessed. The total cholesterol, triglycerides (TG), and high-density lipoprotein (HDL) concentrations were measured in the serum. The total SOD and GPX activities were higher in the SHAM-operated rats than in the DJOS-operated rats. The MnSOD activity was higher in the HFS/HFS than the CD/CD groups. Higher CuZnSOD, GST, GR activities, -SH, and MDA concentrations in the liver, and the triglyceride and cholesterol concentrations in the serum were observed in the SHAM-operated rats than in the DJOS-operated rats. The CAT activity was significantly higher in the HFS-fed rats. Lower TAC and higher TOS values were observed in the SHAM-operated rats. Unhealthy habits after bariatric surgery may be responsible for treatment failure and establishing an obesity condition with increased oxidative stress.

Single anastomosis duodeno-ileal bypass with sleeve gastrectomy generates sustained improvement of glycemic control compared with sleeve gastrectomy in the diet-induced obese rat model.

Bariatric surgery has become a recognized and effective procedure for treating obesity and type 2 diabetes (T2D). Our objective was to directly compare the caloric intake-independent effects of sleeve gastrectomy (SG) and single anastomosis duodenoileal bypass with SG (SADI-S) on glucose tolerance in rats with diet-induced obesity (DIO) and to elucidate the differences between bariatric surgery and caloric restriction.A total of 120 adult male Wistar rats with DIO and insulin resistance were randomly assigned to surgical (sham operation, SG, and SADI-S) and dietary (pair-feeding the amount of food eaten by animals undergoing the SG or SADI-S surgeries) interventions. Body weight and food intake were weekly monitored, and 6weeks after interventions, fasting plasma glucose, oral glucose and insulin tolerance tests, plasma insulin, adiponectin, GIP, GLP-1, and ghrelin levels were determined.The body weight of SADI-S rats was significantly (p < 0.001) lower as compared to the sham-operated, SG, and pair-fed groups. Furthermore, SADI-S rats exhibited decreased whole body fat mass (p < 0.001), lower food efficiency rates (p < 0.001), and increased insulin sensitivity, as well as improved glucose and lipid metabolism compared to that of the SG and pair-fed rats.SADI-S was more effective than SG, or caloric restriction, in improving glycemic control and metabolic profile, with a higher remission of insulin resistance as well as long-term weight loss.

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

AbstractAerobic 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.

Acacia nilotica stem bark extract ameliorates obesity, hyperlipidemia, and insulin resistance in a rat model of high fat diet-induced obesity.

Acacia nilotica (A.nilotica) is an imperative plant with many medicinal uses. The current study aimed to investigate the protective effects of the stem bark of A.nilotica and its fractions in a high fat diet (HFD) rat model. Seventy-two male albino rats were randomly divided into 9 groups, 8 rats per each. Group 1 was the normal control and received standard balanced diet. All the remaining groups were fed HFD for 8 weeks to induce obesity. Group 2 served as the HFD control group, group 3 received orlistat (5mg/kg/day), groups 4 and 5 received total extract of A.nilotica stem bark (250 and 500mg/kg). Groups 6 and 7 received A.nilotica ethyl acetate fraction (250 and 500mg/kg), while groups 8 and 9 received butanol fraction (250 and 500mg/kg). Both doses of the ethyl acetate fraction of the stem bark of A.nilotica significantly decreased the body weight, blood glucose, lipid profile and improved insulin sensitivity. Levels of MDA, leptin and inflammatory cytokines were significantly decreased by the ethyl acetate fraction while adiponectin and HDL-C were significantly increased relative to the HFD control group. Both doses of the ethyl acetate fraction significantly abolished HDF induced oxidative stress and normalized the values of antioxidant enzymes. Furthermore, metabolic profiling of the ethyl acetate fraction was performed by UHPLC/Q-TOF-MS. In conclusion, the ethyl acetate fraction of A.nilotica stem bark possessed antioxidant, anti-inflammatory and insulin sensitizing properties in HFD rat model.

823-P: GLY-200, a Pharmacologic Duodenal Exclusion Therapy, Improved Metabolic Parameters in the DIO Rat

Non-invasive alternatives to metabolic surgery or duodenal exclusion devices for type 2 diabetes (T2D) and obesity are lacking. We developed an orally administered therapeutic polymer, GLY-200, designed to create a barrier in duodenum by complexing with mucin. In healthy subjects, 5 days treatment resulted in significant reductions in postprandial glucose and insulin and increases in bile acids and gut hormones. To evaluate the chronic effects of GLY-200, we conducted an 8-week study in the diet-induced obesity (DIO) rat model. Methods: DIO rats (60% kcal fat diet) were gavaged once daily following a 3-hour fast with GLY-200 (120 mg/rat) or saline (n=12/group). Metabolic assessments included body weight, mesenteric fat mass, skeletal muscle mass (gastrocnemius), glycemic responses to an oral glucose tolerance test (oGTT), and gut hormones from fasted samples at study termination. Results: At 8 weeks, GLY-200 treated rats had a significant reduction in % body weight gain (5%, p &amp;lt; 0.05), lower mesenteric fat mass (p &amp;lt; 0.01), and a significant reduction in incremental glucose AUC0-120 min following the oGTT on Day 51 (p &amp;lt; 0.05) compared to control. These metabolic benefits were associated with a significantly higher fasting active GLP-1 level compared to control (p &amp;lt; 0.01). Trends for increased PYY were also observed as compared to control. There was no difference in skeletal muscle mass. Conclusions: In the DIO rat, chronic (8-weeks) once-daily treatment with GLY-200 resulted in significant improvements in metabolic parameters compared to saline control consistent with a duodenal exclusion MOA. These results support further development of GLY-200 for the treatment of T2D and obesity. Disclosure A.Nimgaonkar: Employee; Glyscend Inc. C.Bryant: Employee; Glyscend Inc. K.M.Habegger: Consultant; Glyscend Inc., Research Support; Eli Lilly and Company, Novo Nordisk, Glyscend Inc., Stock/Shareholder; Glyscend Inc. K.Colbert: Consultant; LifeSprout, Employee; Glyscend Inc. T.Carlson: Employee; Glyscend Inc. S.Polomoscanik: None. J.S.Petersen: None. T.H.Jozefiak: Employee; Glyscend Inc., Stock/Shareholder; Glycologix, LLC. M.Fineman: Employee; Glyscend Inc., Stock/Shareholder; Glyscend Inc.

Ginkgo biloba extract (GbE) restores gut microbiota dysbiosis in a rat model of lard-rich diet-induced obesity

BackgroundGut microbiota (GM) modulation has been considered a nutritional approach to manage obesity. Reduced Firmicutes/Bacteroidetes ratio (F/B) is associated with reduced energy harvesting capacity from the diet, ameliorates endotoxemia and inflammation, and restores gut hormone signaling related to hypothalamic control of energy homeostasis. As anti-obesogenic and anti-inflammatory properties have been attributed to Ginkgo biloba extract (GbE), the present study investigated whether GbE supplementation for two weeks modulates the GM composition of obese rats. MethodFifty-six 2-month-old male Wistar rats were submitted to a lard-rich diet-induced obesity protocol for 60 days (high-fat diet, HFD). Following the obesity-inducing period, rats were gavaged daily with GbE at 500 mg/kg (HFD+G group), or saline (HFD group), for 14 days. A 3rd group (pair-fed group, PF) was performed by mimicking the HFD group (saline administration) but with its food intake matched to the HFD+G group. Rats were euthanized on the 14th supplementation day. Stool DNA was extracted and amplified with V3–V4 region primers of the 16S rRNA gene. ResultsIn comparison to both HFD and PF groups, GbE supplementation increased the number of Bacteroidetes colon community and concomitantly reduced the abundance of Firmicutes, reducing the F/B ratio. Hierarchical clustering showed that communities of the HFD+G group were less likely related to HFD and PF groups. ConclusionAs GbE modulated the GM structure and diversity in GbE-supplemented obese rats, our results show that GbE possesses phytotherapeutic potential to modulate obesity by improving GM and lessening the consequences of obesity-related GM dysbiosis.

Novel insights and mechanisms of diet-induced obesity: Mid-term versus long-term effects on hepatic transcriptome and antioxidant capacity in Sprague-Dawley rats

AimsThe study of molecular mechanisms related to obesity and associated pathologies like type 2-diabetes and non-alcoholic fatty liver disease requires animal experimental models in which the type of obesogenic diet and length of the experimental period to induce obesity deeply affect the metabolic alterations. Therefore, this study aimed to test the influence of aging along a rat model of diet-induced obesity in gene expression of the hepatic transcriptome. Main methodsA high-fat/high-fructose diet to induce obesity was used. Mid- (13 weeks) and long-term (21 weeks) periods were established. Caloric intake, bodyweight, hepatic fat, fatty acid profile, histological changes, antioxidant activity, and complete transcriptome were analyzed. Key findingsExcess bodyweight, hepatic steatosis and altered lipid histology, modifications in liver antioxidant activity, and dysregulated expression of transcripts related to cell structure, glucose & lipid metabolism, antioxidant & detoxifying capacity were found. Modifications in obese and control rats were accounted for by the different lengths of the experimental period studied. SignificanceMain mechanisms of hepatic fat accumulation were de novo lipogenesis or altered fatty acid catabolism for mid- or long-term study, respectively. Therefore, the choice of obesity-induction length is a key factor in the model of obesity used as a control for each specific experimental design.