Rat Model Of Diet-induced Obesity Research Articles

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

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.

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.

Quinoa and Chia Modulate AMPK/PPAR-ɣ Signaling in High-Fat Diet–Induced Obesity Rat Model

Obesity is one of the principal reasons behind a wide range of metabolic diseases and dramatic health complications. Recent studies shed the light on chia (Salvia hispanica L., Lamiaceae) and quinoa (Chenopodium quinoa Willd., Amaranthaceae) seeds and identified them as products of utmost health benefits. The present study was designed to explore the molecular mechanisms of the hydroalcoholic extract of those seeds in weight management. Rats were divided randomly into two main groups: control and treated. The control groups received regular chow diet, high-fat diet, and green tea. The treated groups received high-fat diet and chia or quinoa extracts. Results revealed that the seeds showed hepatoprotective effects and anti-inflammatory and antioxidant activities, and modulated leptin, adiponectin, serum lipid, and glycemic profiles. Effects are further consolidated by normal hepatic tissue architecture upon histopathological examination. Moreover, modulation of peroxisome proliferator-activated receptors-γ transcriptional activity via activation of 5′AMP-activated protein kinase and suppression of nuclear expression of sterol regulatory element-binding protein-1c in obese rats as compared to green tea were demonstrated. Characterization of the major secondary bioactive metabolites was done using HPLC/PDA/ESI-MS/MS. Our study advocates evidence-based study on nutrition and health claims on the use of chia and quinoa extracts as nutraceutical supplements for promoting weight wellness and alleviating its related metabolic disorders.

PD02-02 THE ROLE OF TRANSFORMING GROWTH FACTOR Β IN A PROSTATIC FIBROSIS UNDER SUPPRESSION OF DIHYDROTESTOSTERONE IN HIGH FAT DIET INDUCED OBESITY RAT MODEL

You have accessJournal of UrologyCME1 Apr 2023PD02-02 THE ROLE OF TRANSFORMING GROWTH FACTOR Β IN A PROSTATIC FIBROSIS UNDER SUPPRESSION OF DIHYDROTESTOSTERONE IN HIGH FAT DIET INDUCED OBESITY RAT MODEL Shinsuke Mizoguchi, Kenichi Mori, Hiromitsu Mimata, and Toshitaka Shin Shinsuke MizoguchiShinsuke Mizoguchi More articles by this author , Kenichi MoriKenichi Mori More articles by this author , Hiromitsu MimataHiromitsu Mimata More articles by this author , and Toshitaka ShinToshitaka Shin More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003219.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Although 5 alpha reductase inhibitors (5ARIs) can reduce prostatic volume by blocking production of dihydrotestosterone (DHT) and is widely used to treat symptomatic benign prostatic hyperplasia (BPH), the histological response to the treatment by 5ARIs is often heterogeneous and lower urinary tract symptoms can persist. Thus, a 5ARIs induced pathway related to treatment refractory is supposed to exist. To elucidate the pathways implicated to unsuccessful treatment for BPH patients, this study investigated changes in morphological and gene expression profiles in the prostate under DHT suppression using high fat diet induced obesity rat model. METHODS: Male Wistar rats at 8 weeks old were divided into four groups; rats with normal diet group (ND, n=5), rats with high fat diet induced obesity group (HFD, n=5), HFD treated by dutasteride (D, n=4), and HFD treated by dutasteride and tranilast (D+T, n=4), which is known to inhibit TGFβ. The high fat diet contains 32% fat. These rats were maintained for twelve weeks followed by two weeks treatment by oral administration of placebo or dutasteride (0.5 mg/kg) or tranilast (150 mg/kg) daily. Lateral lobes of prostate were harvested to evaluate prostatic weight, histological change and mRNA expression of IL1β and TGFβ in the prostate by qPCR. RESULTS: HFD showed significantly increased body weight, visceral fat and prostatic weight as well as significant upregulation of gene expressions in IL1β and TGFβ compared to ND. In contrast, HFD treated by dutasteride demonstrated significantly decreased prostatic weight in association with downregulation of IL1β and upregulation of TGFβ with compared to HFD with placebo. Furthermore, dutasteride administration induced prostatic fibrosis as evidenced by masson trichrome staining whereas the addition of tranilast to dutasteride suppressed prostatic tissue fibrosis in association with reduced weight of prostatic tissue and downregulation of TGFβ in group D+T compared to group D. CONCLUSIONS: This study demonstrated prostatic fibrosis in association with upregulation of TGFβ as well as decreased prostatic weight and improvement of prostatic fibrosis by TGFβ inhibition. These results suggest that TGFβ signaling has an important role in development of prostatic fibrosis under 5ARIs treatment possibly leading to treatment refractory. Therefore, TGFβ signaling pathway could be an therapeutic target for BPH. Source of Funding: JSPS KAKENHI Grant Number 20K18094 © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e69 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Shinsuke Mizoguchi More articles by this author Kenichi Mori More articles by this author Hiromitsu Mimata More articles by this author Toshitaka Shin More articles by this author Expand All Advertisement PDF downloadLoading ...

Differential disruption on glucose and insulin metabolism in two rat models of diet-induced obesity, based on carbohydrates or lipids.

Obesity is a relevant health public issue and is the main factor for glucose metabolism dysregulation and diabetes progression; however, the differential role of a high-fat diet or high sugar diet consumption on glucose metabolism and insulin processing is not well understood and has been scarcely described. Our research aimed to analyze the effects of chronic consumption of both high sucrose and high-fat diets on glucose and insulin metabolism regulation. Wistar rats were fed with high-sugar or high-fat diets for 12months; after that, fasting glucose and insulin levels were measured along with a glucose tolerance test (GTT). Proteins related to insulin synthesis and secretion were quantified in pancreas homogenates, whereas islets were isolated to analyze ROS generation and size measurement. Our results show that both diets induce metabolic syndrome, linked with central obesity, hyperglycemia, and insulin resistance. We observed alterations in the expression of proteins related with insulin synthesis and secretion, along with diminution of Langerhans islets size. Interestingly, the severity and number of alterations were more evident in the high-sugar diet than in the high-fat diet group. In conclusion, obesity and glucose metabolism dysregulation induced by carbohydrate consumption, led to worst outcomes than high-fat diet.

Effects of Melatonin Supplementation on the Aortic Wall in a Diet-Induced Obesity Rat Model.

Background Cardiovascular disease (CVD) is still the leading cause of death globally. Alterations in the arterial wall architecture predict CVD morbidity and mortality and are associated with other CVD risk factors. Aortic wall thickness is closely linked to short- and long-term CVD morbidity and mortality, even without pronounced atherosclerotic changes.Obesity increases the risk of a broad spectrum of pathologies with vascular manifestation,which are oftenpathogenically associated with chronic oxidative stress and inflammatory response. Hence, as an antioxidant and anti-inflammatory agent, the pineal gland hormone melatonin is expected to have vasoprotective effects. This study evaluated the effects of melatonin supplementation on aortic wall thickness by assessing the cross-sectional associations of abdominal obesity with aortic intima-media thickness in a diet-induced obesity rat model. Methodology The model comprised of male Wistar rats that were on a high-fructose diet (HFD) (20% glucose-fructose corn syrup) for 12 weeks; the rats were divided into four groups (n = 8): control, HFD, HFD and melatonin supplementation (per os- 4 mg/kg/24h), and control and melatonin supplementation. All rats received a standard rodent diet and tap water. Zoometric measurements and the Lee index were calculated. Morphometric analysis of the abdominal aorta was performed by staining with hematoxylin-eosin and measuring the thickness of the abdominal aortic wall. For this, we used the Aperio Image Scope software. To evaluate the functional properties of the abdominal aorta, the modified Kernogan's index (KI) was employed. Results The results showed significantly elevated body weight (Lee index), KI, and wall thickness of the aorta abdominalis with morphometric changes in the vessel wall in HFD rats compared to the control group. Melatonin supplementation prevented these changes. Conclusions The administration of HFD to Wistar rats led to pathomorphological and morphometric changes in their abdominal aorta, which constitute the main diagnostic criteria of endothelial dysfunction. Melatonin supplementation regressed vascular wall remodeling and restored its functional capacity.

Increased Glucagon Immunoreactivity in a Rat Model of Diet-Induced Obesity following Sleeve Gastrectomy

Objective: Bariatric surgery is currently the most effective treatment for obesity, and procedures such as Roux-en-Y gastric bypass and sleeve gastrectomy (SG) also result in rapid improvements in insulin sensitivity and glucose tolerance. In addition, these procedures cause changes in the secretion of various gut-derived hormones. The role these hormones play in the mechanism of the beneficial effects of bariatric surgery is still debated, but nonetheless, their importance provides inspiration for novel obesity-targeted pharmacotherapies. Methods: Male Sprague-Dawley rats were fed either regular chow or a cafeteria diet to induce obesity. A sub-group of the obese animals then underwent either sham surgery or SG. Results: Following a 4-week recovery period, SG rats weighed significantly less than obese or sham-operated rats. Improvements in glucose tolerance and insulin sensitivity also occurred in the SG group, but these were not always statistically significant. We measured the intracellular lipid content of liver samples and found that obese rats showed signs of non-alcoholic fatty liver disease, which were significantly ameliorated by SG. There were significantly higher glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide responses to a standard mixed meal in the SG group, as well as paradoxically higher glucagon secretion. Conclusion: These data highlight the need for more specific anti-glucagon antibodies to characterize the changes in proglucagon-derived peptide concentrations that occur following SG. Further studies are required to determine whether these peptides contribute to the therapeutic effects of SG.

Effects of protein intake from an energy-restricted diet on the skeletal muscle composition of overweight and obese rats

Excess weight and obesity are often associated with ectopic adipose tissue accumulation in skeletal muscles. Intermuscular adipose tissue (IMAT) impairs muscle quality and reduces insulin-stimulated skeletal muscle glucose uptake. Although energy restriction and high protein intake can decrease IMAT, the effects and mechanisms of protein intake from an energy-restricted diet on protein and fat masses in skeletal muscle have received little attention. After establishing a diet-induced overweight and obese Sprague-Dawley rat model (half male and half female), rats were divided into five groups: normal control (NC; normal weight, general maintenance diet), model control (MC; overweight and obesity, high-fat diet), energy-restricted low protein (LP; overweight and obesity, 60% energy intake of NC, general maintenance diet), energy-restricted normal protein (NP; overweight and obesity, 60% energy intake of NC, high-protein diet 1), and energy-restricted high protein (HP; overweight and obesity, 60% energy intake of NC, high-protein diet 2). After 8 weeks, plasma and skeletal muscle (quadriceps femoris and gastrocnemius) samples were collected. Plasma levels of glucose, triglycerides, and hormones were analyzed, while contents of protein, fat, and factors associated with their synthesis and degradation were evaluated in skeletal muscles. Plasma concentrations of hormones contrasted protein and fat contents in skeletal muscles. Fat weights and contents of quadriceps femoris and gastrocnemius muscles in the NP group were significantly lower compared with LP and HP groups (P < 0.05). Moreover, concentrations of factors associated with the degradation of muscle fat were significantly higher in the NP group compared with LP and HP groups (P < 0.05). During energy restriction, protein intake equal to that of a normal protein diet increased lipolysis of quadriceps femoris and gastrocnemius muscles in rats of both sexes.

Effects of growth hormone on lipid metabolism and sexual development in pubertal obese male rats.

To investigate the effects of growth hormone (GH) on pubertal obese male rats, a rat model of high-fat diet-induced obesity was established in juvenile male rats. The model rats were divided into the treatment group (GH) and the non-treatment group (physiological saline). After 4 weeks, we measured the levels of alanine transaminase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), estrogen (E2), testosterone (T), and insulin-like growth factor (IGF-1). The morphological changes of the liver and testis were assessed, and the expression of aromatase was detected. The levels of ALT, AST, TC, TG, LDL-C, E2, and IGF-1 in the treatment group were significantly lower than in the non-treated model rats (P < 0.001). The levels of HDL-C and T of GH-treated rats were significantly higher than those of the non-treatment group (P < 0.001). Compared with non-treated model rats, GH-treated model rats showed reduced liver steatosis, improved morphological structure of the testicular seminiferous tubules, and an increased number of spermatogenic cells. The treatment group also showed lower expression of aromatase in the liver and testis compared with the non-treatment group. GH partially protected pubertal male rats from obesity-induced lipid metabolic disorder and sexual retardation.

Anti-Inflammatory Protein Isolated from Tamarind Promotes Better Histological Aspects in the Intestine Regardless of the Improvement of Intestinal Permeability in a Preclinical Study of Diet-Induced Obesity.

Obesity is associated with metabolic and physiological effects in the gut. In this study, we evaluated the anti-inflammatory effect of trypsin inhibitor isolated from tamarind seeds (TTI) in vitro (interaction with lipopolysaccharide (LPS) and inhibitory activity against human neutrophil elastase (HNE)), and using intestinal co-cultures of Caco-2:HT29-MTX cell lines inflamed with TNF-α (50 ng/mL) and a Wistar rat model of diet-induced obesity (n = 15). TTI was administered to animals by gavage (10 days), and the treated group (25 mg/kg/day) was compared to animals without treatment or treated with a nutritionally adequate diet. In the in vitro study, it showed inhibitory activity against HNE (93%). In co-cultures, there was no protection or recovery of the integrity of inflamed cell monolayers treated with TTI (1.0 mg/mL). In animals, TTI led to lower plasma concentrations of TNF-α and IL-6, total leukocytes, fasting glucose, and LDL-c (p &lt; 0.05). The intestines demonstrated a lower degree of chronic enteritis, greater preservation of the submucosa, and greater intestinal wall thickness than the other groups (p = 0.042). Therefore, the better appearance of the intestine not reflected in the intestinal permeability added to the in vitro activity against HNE point to possibilities for new studies and applications related to this activity.

Compulsive-like eating of high-fat high-sugar food is associated with 'addiction-like' glutamatergic dysfunction in obesity prone rats.

Chronic overeating is a core feature of diet‐induced obesity. There is increasing evidence that in vulnerable individuals, such overeating could become compulsive, resembling an addictive disorder. The transition to compulsive substance use has been linked with changes at glutamatergic synapses in the nucleus accumbens. In this study, we investigated a potential link between such glutamatergic dysregulation and compulsive‐like eating using a rat model of diet‐induced obesity. A conditioned suppression task demonstrated that diet‐induced obese rats display eating despite negative consequences, as their consumption was insensitive to an aversive cue. Moreover, nucleus accumbens expression of GluA1 and xCT proteins was upregulated in diet‐induced obese animals. Lastly, both a computed ‘addiction score’ (based on performance across three criteria) and weight gain were positively correlated with changes in GluA1 and xCT expression in the nucleus accumbens. These data demonstrate that the propensity for diet‐induced obesity is associated with compulsive‐like eating of highly palatable food and is accompanied by ‘addiction‐like’ glutamatergic dysregulation in the nucleus accumbens, thus providing neurobiological evidence of addiction‐like pathology in this model of obesity.

Synbiotics intake improves disturbed metabolism in a rat model of high fat diet-induced obesity; A potential role of adipose tissue browning

Browning of white adipose tissue (WAT) is currently considered a potential therapeutic approach to treat or prevent diet-induced obesity. Synbiotics have protective effects against diet-induced obesity; however, its role in adipose tissue browning has been less investigated. to study the possible effect of synbiotics intake on browning of WAT in obese rats. Twenty-four adult male Wistar rats were randomly divided into four groups; normal diet (ND) control group, high fat diet (HFD) group, ND group receiving synbiotics, and HFD group receiving synbiotics. After eight weeks, all rats were sacrificed; and samples (blood, WAT, brown adipose tissue, and liver) were collected. Lipid profile, liver enzymes, fasting glucose, and fasting insulin levels were measured. The expression of browning-related genes: uncoupler protein-1 (UCP-1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), and peroxisome proliferator-activated receptors gamma (PPARγ) were measured by real-time polymerase chain reaction (PCR) in adipose tissues. Fibroblast growth factor 21 (FGF21) protein level was measured in serum, adipose and liver tissues, and FGF21 receptor expression was performed by real-time PCR in adipose tissues. ynbiotics intake was associated with improvement in lipid profile, liver enzymes, and insulin sensitivity in HFD rats. Moreover, the intake was associated with higher gene expression of brown adipocyte-specific markers. As for the FGF21 and its receptor, intriguing results were obtained that needs further in-depth studies. synbiotics might protect against diet-induced obesity through induction of thermogenic genes resulting in brown-like adipocyte phenotype in WAT.