Rat Model Of Diet-induced Obesity Research Articles

N-acetylcysteine reduces addiction-like behaviour towards high-fat high-sugar food in diet-induced obese rats.

Compulsive forms of eating displayed by some obese individuals share similarities with compulsive drug-taking behaviour, a hallmark feature of substance use disorder. This raises the possibility that drug addiction treatments may show utility in the treatment of compulsive overeating. N-Acetylcysteine (NAC) is a cysteine pro-drug which has experienced some success in clinical trials, reducing cocaine, marijuana and cigarette use, as well as compulsive behaviours such as gambling and trichotillomania. We assessed the impact of NAC on addiction-like behaviour towards highly palatable food in a rat model of diet-induced obesity. Adult male Sprague-Dawley rats were placed on a high-fat high-sugar diet for 8weeks and then assigned to diet-induced obesity-prone (DIO) or diet-induced obesity-resistant (DR) groups based on weight gain. DIO and DR rats were subjected to an operant conditioning paradigm whereby rats could lever press for high-fat high-sugar food pellets. This alternated with periods of signalled reward unavailability. Before treatment DIO rats ate more in their home cage, earned more food pellets in operant sessions, and responded more during periods that signalled reward unavailability (suggestive of compulsive-like food seeking) compared with DR rats. This persistent responding in the absence of reward displayed by DIO rats was ameliorated by daily injections of NAC (100mg/kg, i.p.) for 14days. By the end of the treatment period, lever-pressing by NAC-treated DIO rats resembled that of DR rats. These findings suggest that NAC reduces addiction-like behaviour towards food in rats and supports the potential use of this compound in compulsive overeating.

Contractility of permeabilized rat vastus intermedius muscle fibres following high-fat, high-sucrose diet consumption.

Obesity is a worldwide health concern associated with impaired physical function. It is not clear if contractile protein dysfunction contributes to the impairment of muscle function observed with obesity. The purpose of this study was to examine if diet-induced obesity affects contractile function of chemically permeabilized vastus intermedius fibres of male Sprague-Dawley rats expressing fast myosin heavy chain (MHC) IIa or slow MHC I. Rats consumed either a high-fat, high sucrose (HFHS) diet or a standard (CHOW) diet beginning as either weanlings (7-week duration: WEAN7 cohort, or 14-week duration: WEAN14 cohort) or young adults (12-week duration: ADULT12 cohort, 24-week duration: ADULT24 cohort). HFHS-fed rats had higher (P < 0.05) whole-body adiposity (derived from dual-energy X-ray absorptiometry) than CHOW-fed rats in all cohorts. Relative to CHOW diet groups, the HFHS diet was associated with impaired force production in (a) MHC I fibres in the ADULT24 cohort; and (b) MHC IIa fibres in the ADULT12 and ADULT24 cohorts combined. However, the HFHS diet did not significantly affect the Ca2+-sensitivity of force production, unloaded shortening velocity, or ratio of active force to active stiffness in any cohort. We conclude that diet-induced obesity can impair force output of permeabilized muscle fibres of adult rats. Novelty: We assessed contractile function of permeabilized skeletal muscle fibres in a rat model of diet-induced obesity. The high-fat, high-sucrose diet was associated with impaired force output of fibres expressing MHC I or MHC IIa in some cohorts of rats. Other measures of contractile function were not significantly affected by diet.

Diallyl Trisulfide Prevents Obesity and Decreases miRNA-335 Expression in Adipose Tissue in a Diet-Induced Obesity Rat Model.

Diallyl trisulfide (DATS), an organosulfur compound generates in crushed garlic, has various beneficial health effects. A growing body of evidence indicates that miRNAs are involved in the pathology of lifestyle diseases including obesity. The anti-obesogenic effect of garlic is previously reported; however, the effects of DATS on obesity, and the relationship between garlic compounds and the involvement of miRNA remains unclear. Here, the anti-obesogenic activity of DATS and the potential role of miRNA in a diet-induced obesity rat model are investigated. Oral administration of DATS suppressed body and white adipose tissue (WAT) weight gain in rats fed a high-fat diet compared with vehicle-administered rats. DATS lowered the plasma and liver triglyceride levels in obese rats, and decreased lipogenic mRNA levels including those of Srebp1c, Fasn, and Scd1 in the liver. DATS also suppressed de novo lipogenesis in the liver. Transcriptomic analyses of miRNA and mRNA in the epididymal WAT of obese rats using microarrays revealed that DATS decreased miRNA-335 expression and normalized the obesity-related mRNA transcriptomic signatures in epididymal WAT. The potent anti-obesogenic effects of DATS and its possible mechanism of action was clearly demonstrated in this study.

Effects of Dietary Butyrate on Diet-Induced Obesity and Lipid Metabolism

Abstract Objectives We examined the effects of dietary butyrate, a short-chain fatty acids (SCFAs) on body weight control and metabolism in a diet-induced obesity rat model. Methods Male Sprague-Dawley rats fed with high-fat diet for 14 weeks. Sodium butyrate was administrated through diet supplementation at 3% wt/wt for long-term (14 weeks) or drinking water at 1% for short-term (2 weeks). Serum and feces were collected. Colon and liver tissues used for analyzing mRNA expression. To assess the effects of butyrate on lipid metabolism, 3T3-L1 cells were treated with sodium butyrate and sodium-3-hyroxybutyrate during adipogenic differentiation. Results On the high-fat diet, dietary supplementation of butyrate protected against body weight gain. Interestingly, food intake was increased and consistently colonic Proglucagon (Gcg), encoding Glucagon-like Peptide-1 (GLP-1) involved in appetite-suppression, was decreased. In contrast, short-term administration of butyrate did not affect body weight and food intake. Free fatty acid receptor 2 (Ffar2), a G-protein coupled receptor recognizing SCFAs and stimulating GLP-1 production, was decreased in colon. The colonic Hydroxycarboxylic acid receptor 2 (Hcar2) and Tight junction protein-1 (Tjp1) marginally increased but expression of inflammatory cytokines was not altered, implicating that anti-obesity effects of butyrate were not primarily through colon. In the liver, butyrate showed significantly decreased Ffar2 and Peroxisome proliferator–activated receptor-γ (Ppar-γ). In the butyrate group, aberrant phenotypes were observed including hyperlipidemia and alteration of serum level of adiponectin without change in fecal energy density. Intriguingly, in the 3T3-L1 cell line, fat accumulation was significantly stimulated at lower concentration of butyrate with elevated expression of Ffar2 and Ppar-γ. High concentration of butyrate reduced Ffar2 and Ppar-γ and suppressed adipocytic fat accumulation. Conclusions Our results suggested that dietary butyrate prevented diet-induced obesity despite increased food intake. Moreover, butyrate may regulate lipid metabolism in a dose-dependent manner. Funding Sources This research was supported by Basic Science Research Program through the NRF funded by the Ministry of Education. J.S is grateful for financial support from Hyundai Motor Chung Mong-Koo Foundation.

Attenuation of Oxidative Stress and Inflammatory Response by Chronic Cannabidiol Administration Is Associated with Improved n-6/n-3 PUFA Ratio in the White and Red Skeletal Muscle in a Rat Model of High-Fat Diet-Induced Obesity.

The consumption of fatty acids has increased drastically, exceeding the nutritional requirements of an individual and leading to numerous metabolic disorders. Recent data indicate a growing interest in using cannabidiol (CBD) as an agent with beneficial effects in the treatment of obesity. Therefore, our aim was to investigate the influence of chronic CBD administration on the n-6/n-3 polyunsaturated fatty acids (PUFAs) ratio in different lipid fractions, inflammatory pathway and oxidative stress parameters in the white and red gastrocnemius muscle. All the designed experiments were performed on Wistar rats fed a high-fat diet (HFD) or a standard rodent diet for seven weeks and subsequently injected with CBD (10 mg/kg once daily for two weeks) or its vehicle. Lipid content and oxidative stress parameters were assessed using gas–liquid chromatography (GLC), colorimetric and/or immunoenzymatic methods, respectively. The total expression of proteins of an inflammatory pathway was measured by Western blotting. Our results revealed that fatty acids (FAs) oversupply is associated with an increasing oxidative stress and inflammatory response, which results in an excessive accumulation of FAs, especially of n-6 PUFAs, in skeletal muscles. We showed that CBD significantly improved the n-6/n-3 PUFA ratio and shifted the equilibrium towards anti-inflammatory n-3 PUFAs, particularly in the red gastrocnemius muscle. Additionally, CBD prevented generation of lipid peroxidation products and attenuated inflammatory response in both types of skeletal muscle. In summary, the results mentioned above indicate that CBD presents potential therapeutic properties with respect to the treatment of obesity and related disturbances.

The TOTUM-63 Supplement and High-Intensity Interval Training Combination Limits Weight Gain, Improves Glycemic Control, and Influences the Composition of Gut Mucosa-Associated Bacteria in Rats on a High Fat Diet.

Obesity and prediabetes are the two strongest risk factors of type 2 diabetes. It has been reported that TOTUM-63, a polyphenol-rich plant extract, has beneficial effects on body weight (BW) and insulin resistance in mice fed a high fat diet (HFD). The study aim was to determine whether high-intensity interval training (HIIT) and/or TOTUM-63 supplementation improved body composition and glycemic control and gut microbiota composition in a Western diet-induced obesity rat model. Wistar rats received a standard diet (CTRL; control; n = 12) or HFD (HFD; n = 48) for 16 weeks. Then, HFD rats were divided in four groups: HFD, HFD + TOTUM-63 (T63), HFD + HIIT (HIIT), and HFD + HIIT +T63 (HIIT + T63). Training was performed 4 days/week for 12 weeks. TOTUM-63 was included in diet composition (2%). The HIIT + T63 combination significantly limited BW gain, without any energy intake modulation, and improved glycemic control. BW variation was correlated with increased α-diversity of the colon mucosa microbiota in the HIIT + T63 group. Moreover, the relative abundance of Anaeroplasma, Christensenellaceae and Oscillospira was higher in the HIIT + T63 group. Altogether, these results suggest that the HIIT and TOTUM-63 combination could be proposed for the management of obesity and prediabetes.

Effects of Ovariectomy and Exercise Training on Mineral Status in a High-Fat Diet-Induced Obesity Rat Model.

Osteoporosis is a growing public health issue for an aging society. Previous studies have found both beneficial and detrimental effects of obesity on bone health. The purpose of this study was to investigate the impact of estrogen deficiency and physical activity on bone and blood concentrations of macrominerals (Ca, P, and Mg) and microminerals (Zn, Se, Cu, and Fe) in a high-fat diet-induced obesity rat model. Forty-eight female Wistar rats were divided into six groups: sham-operated and ovariectomized rats that received a standard diet (SD), high-fat diet (HFD), or HFD accompanied by physical exercise. The effect of ovariectomy on bone minerals varied with diet. Ovariectomy significantly decreased femoral Ca and Mg in sedentary rats receiving a SD; femoral Se, Cu, Zn, and Fe in sedentary rats on HFD; and plasma Fe in both sedentary rats on SD and exercising rats on HFD. The interaction of ovariectomy and diet had the strongest impact on Mg and Se concentrations in femur. In ovariectomized rats, HFD showed to have a protective effect on bone mineralization (femoral Ca and Mg), and a negative one on antioxidant microminerals (femoral Se, Cu, and Zn). Physical activity reduced the decline of Se, Cu, Zn, and Fe in the femur of ovariectomized rats on HFD. In the current state of knowledge, it is difficult to suggest if decreased femoral levels of antioxidant microminerals may contribute to the pathophysiology of osteoporosis in obese individuals or just reflect the mineral status in the body.

Proteomic and Structural Manifestations of Cardiomyopathy in Rat Models of Obesity and Weight Loss.

Obesity cardiomyopathy increases the risk of heart failure and death. Obesity is curable, leading to the restoration of the heart phenotype, but it is not clear if there are any after-effects of obesity present after weight loss. We characterize the proteomic landscape of obesity cardiomyopathy with an evaluation of whether the cardiac phenotype is still shaped after weight loss. Cardiomyopathy was validated by cardiac hypertrophy, fibrosis, oversized myocytes, and mTOR upregulation in a rat model of cafeteria diet-induced developmental obesity. By global proteomic techniques (LC-MS/MS) a plethora of molecular changes was observed in the heart and circulation of obese animals, suggesting abnormal utilization of metabolic substrates. This was confirmed by increased levels of cardiac ACSL-1, a key enzyme for fatty acid degradation and decreased GLUT-1, a glucose transporter in obese rats. Calorie restriction and weight loss led to the normalization of the heart’s size, but fibrosis was still excessive. The proteomic compositions of cardiac tissue and plasma were different after weight loss as compared to control. In addition to morphological consequences, obesity cardiomyopathy involves many proteomic changes. Weight loss provides for a partial repair of the heart’s architecture, but the trace of fibrotic deposition and proteomic alterations may occur.

Tart cherry (Prunus cerasus L.) dietary supplement modulates visceral adipose tissue CB1 mRNA levels along with other adipogenesis-related genes in rat models of diet-induced obesity.

There is increasing evidence for the involvement of dietary bioactive compounds in the cross-talk modulation of endocannabinoid system and some of the key regulators of transcriptional control for adipogenesis. We aimed to characterize the expression of cannabinoid CB1/CB2 receptors and fatty acid amide hydrolase (FAAH) along with selected adipogenesis-related genes (PPARγ, SREBP-1c and PREF-1), adipocyte-secreted factors (leptin and adiponectin), mitochondrial bioenergetic modulators (PGC-1A and UCP-2), and transient receptor potential vanilloid subtype 1 (TRPV1) and 2 (TRPV2) channels in visceral adipose tissue of rats fed with a high-fat diet (HFD) containing either tart cherry seeds alone or tart cherry seeds and juice for 17weeks. The visceral adipose tissue was weighed and checked the expression of different markers by qRT-PCR, Western blot and immunohistochemistry. Tart cherry supplements were able to downregulate the HFD-induced mRNA expression of CB1 receptor, SREBP-1c, PPARγ, leptin, TRPV1 and TRPV2 resulting in potential anti-adipogenic effects. The present study points out that the intake of bioactive constituents of tart cherry may attenuate the effect of adipogenesis by acting directly on the adipose tissue and modulating the interplay between CB1, PPARγ and TRPV channel gene transcription.

Effects of Zingiber officinale extract supplementation on metabolic and genotoxic parameters in diet-induced obesity in mice.

Obesity is an epidemic associated with many diseases. The nutraceutical Zingiber officinale (ZO) is a potential treatment for obesity; however, the molecular effects are unknown. Swiss male mice were fed a high-fat diet (59 % energy from fat) for 16 weeks to generate a diet-induced obesity (DIO) model and then divided into the following groups: standard diet + vehicle; standard diet + ZO; DIO + vehicle and DIO + ZO. Those in the ZO groups were supplemented with 400 mg/kg per d of ZO extract (oral administration) for 35 d. The animals were euthanised, and blood, quadriceps, epididymal fat pad and hepatic tissue were collected. DIO induced insulin resistance, proinflammatory cytokines, oxidative stress and DNA damage in different tissues. Treatment with ZO improved insulin sensitivity as well as decreased serum TAG, without changes in body weight or adiposity index. TNF-α and IL-1β levels were lower in the liver and quadriceps in the DIO + ZO group compared with the DIO group. ZO treatment reduced the reactive species and oxidative damage to proteins, lipids and DNA in blood and liver in obese animals. The endogenous antioxidant activity was higher in the quadriceps of DIO + ZO. These results in the rat model of DIO may indicate ZO as an adjuvant on obesity treatment.

Tinospora cordifolia ameliorates brain functions impairments associated with high fat diet induced obesity

Obesity is a rapidly growing health problem worldwide and its prevalence has increased markedly in both the developing and developed nations. It is associated with a range of co-morbidities such as cardiovascular disease, type 2 diabetes mellitus, and cognitive dysfunctions. Therefore, the need for a safe and effective treatment has led to the exploration of natural products for the management of obesity. In the present study, we tested the anxiolytic, anti-apoptotic, and anti-neuroinflammatory potential of Tinospora cordifolia in a high fat diet-induced obesity rat model system. Young female Wistar albino rats were divided into three groups: (1) Low fat diet (LFD), fed on normal chow feed; (2) High fat diet (HFD), fed on diet containing 30% fat by weight; and (3) High fat diet containing extract (HFDE), fed on high fat diet supplemented with the stem powder of T. cordifolia (TCP). The rats from each group were kept on their respective feeding regimen for 12 weeks. The body weight and calorie intake were recorded weekly. The elevated plus maze test and rotarod performance test were performed to evaluate the anxiety-like behavior and locomotor coordination, respectively. The levels of serum cytokines (IL-6 and TNF-α) were estimated and various markers for inflammation, synaptic plasticity, apoptosis, and energy homeostasis were studied by western blotting. The HFDE rats showed reduced anxiety-like behavior and improved locomotor behavior as compared to HFD-induced obese rats. The TCP supplementation in high fat diet suppressed the expression of inflammatory molecules, including serum cytokines (IL-6 and TNF-α), and modulated apoptosis and synaptic plasticity. TCP was found to be effective in managing body weight in HFD-fed rats by maintaining energy metabolism and cellular homeostasis. T. cordifolia may be recommended as a potential therapeutic agent to prevent the adverse effects of obesity and obesity-associated brain dysfunctions.

Myrrh essential oil-based nanolipid formulation for enhancement of the antihyperlipidemic effect of atorvastatin

Obesity is a growing health problem and a significant contributor to the global burden of disease. Statins have shown efficacy in modulating the mortality risk associated with obesity. Myrrh has recently been proven to reduce body weight gain and improve lipid profiles in obese hyperlipidemic rats. The aim of this study was to formulate and evaluate the anti-obesity potential of a myrrh oil-based nanoemulsion containing the hypolipidemic agent, atorvastatin. A two-factor, three-level, full factorial design was adopted to formulate and optimize the nanoemulsion formulations. The prepared formulations were characterized in terms of drug-excipient compatibility studies, physical appearance, rheological behavior, in vitro drug release, stability, and in vivo anti-obesity potential. The prepared nanoemulsion formulations showed a uniform size distribution with a droplet size within the nano-size range. The release of drug from the nanoemulsion formulations was dependent on the surfactant concentration used. Interestingly, all developed nanoemulsions were stable for up to 3 months upon storage at refrigerator and room temperature. Most importantly, in the high-fat diet-induced obesity rat model, addition of myrrh oil to oleic acid as an oily phase for nanoemulsion showed a synergistic effect to the anti-obesity potential of the hypolipidemic drug atorvastatin. In conclusion, formulating atorvastatin into a myrrh oil-based nanoemulsion might represent a promising approach for augmenting the anti-obesity action of atorvastatin, not only by enhancing its systemic bioavailability, but also by gaining the benefit of the synergistic anti-obesity effect of myrrh oil.

Transcriptomic changes in pancreatic islets, adipose and liver after Roux-en-Y gastric bypass in a diet-induced obese rat model

Roux-en-Y gastric bypass (RYGB) is the most efficient intervention in morbid obesity and promotes metabolic improvements in several peripheral tissues. However, the underlying molecular mechanisms are still poorly understood. To further understand the effects of RYGB on peripheral tissues transcriptomes, we determined transcriptome signatures in pancreatic islets, adipose and liver tissue from diet-induced obese (DIO) rats model following RYGB. Whereas RYGB led to discrete gene expression changes in pancreatic islets, substantial transcriptome changes were observed in metabolic and immune signaling pathways in adipose tissue and the liver, indicating major gene adaptive responses in fat-storing tissues. Compared to RYGB DIO rats, peripheral tissue transcriptome signatures were markedly different in caloric restricted weight matching DIO rats, implying that caloric restriction paradigms do not reflect transcriptomic regulations of RYGB induced weight loss. The present gene expression study may serve as a basis for further investigations into molecular regulatory effects in peripheral tissues following RYGB-induced weight loss.

The Effect of Brown Rice on Superoxide Dismutase Level and Non-alcoholic Fatty Liver in an Sprague–Dawley Rat Model of High-fat High-fructose Diet-induced Obesity

BACKGROUND: Obesity can cause oxidative stress due to the release of free radical components or reactive oxygen species. The accumulation of excess fat in obesity also causes the occurrence of non-alcoholic fatty liver. Brown rice is a functional food with higher fiber, vitamin, mineral, and antioxidant contents than those in white rice. &#x0D; AIM: This study was aimed to evaluate the effect of brown rice on the superoxide dismutase (SOD) level and non-alcoholic fatty liver in obese Sprague–Dawley rats.&#x0D; METHODS: An experimental study using a post-test-only control group design was carried out on a Sprague–Dawley rat model of obesity-induced by a high-fat high fructose (HFHF) diet. Sample selection was done through simple random sampling; rats were divided into five groups, namely the normal diet group (K−), the HFHF diet group (K+), and HFHF diet groups with the addition of brown rice dose I (P1), dose II (P2), and dose III (P3). The measured variable was the SOD level measured using the spectrophotometric method and the calculation of the percentage of fatty liver cells on the results of a hematoxylin-eosin liver scan of a rat’s right lobe.&#x0D; RESULTS: The dose of brown rice was not affected body weight of the rats significantly compared to the control groups. Then, there were significant differences in the SOD level and fatty liver in at least two groups (p = 0.01 and p = 0.001).&#x0D; CONCLUSION: This study concludes that the administration of brown rice contributes to the increasing SOD level and decreasing fatty liver in obese model rats.

Ameliorative effect of selegiline in high fat diet induced obesity rat model: Possible role of dopaminergic pathway

ObjectivesDopamine a neurotransmitter plays an important role in food regulation. Various reports revealed that suppression of dopamine results in pathological overeating. Monoamine oxidase type B (MAO-B) inhibitor selegiline (SG) increases the level of dopamine in the brain. Thus, the current study was designed to examine whether selegiline (SG) could attenuate the development of experimental obesity and to explore the possible involvement of dopamine in high fat diet (HFD) induced obesity. Materials and methodsCurrent study illustrates importance of administrating SG (10 and 20 mg kg−1 day−1, p. o.) alone and SG (20 mg kg−1 day−1, p. o) in combination with chlorpromazine (CPZ) (6 mg kg−1 day−1p.o) in obesity. The SG and its combination with CPZ were given orally for 6 weeks along with high fat diet to the obese rats. The body weight, feed intake (Kcal), weight and size of fat pads, levels of serum glucose, triglycerides (TG), total cholesterol (TC), low density lipoprotein (LDL), very low-density lipoprotein VLDL and high density lipoproteins (HDL) were estimated as parameters of obesity. ResultsOral administration of SG (10 and 20 mg kg−1day−1) significantly reduced (p < 0.05) body weight gain, feed intake (Kcal), weight and size of fat pads, levels of serum glucose, TG, TC, LDL, VLDL in obese rats. Furthermore, Dopaminergic antagonist CPZ in combination with SG declines the beneficial effects of SG in obese rats. ConclusionThe present study demonstrates the involvement of dopaminergic pathway and beneficial effects of dopamine enhancer SG in HFD induced obesity.

Chronic Cannabidiol Administration Attenuates Skeletal Muscle De Novo Ceramide Synthesis Pathway and Related Metabolic Effects in a Rat Model of High-Fat Diet-Induced Obesity.

Numerous studies showed that sustained obesity results in accumulation of bioactive lipid derivatives in several tissues, including skeletal muscle, which further contributes to the development of metabolic disturbances and insulin resistance (IR). The latest data indicate that a potential factor regulating lipid and glucose metabolism is a phytocannabinoid—cannabidiol (CBD), a component of medical marijuana (Cannabis). Therefore, we aimed to investigate whether chronic CBD administration influences bioactive lipid content (e.g., ceramide (CER)), as well as glucose metabolism, in the red skeletal muscle (musculus gastrocnemius) with predominant oxidative metabolism. All experiments were conducted on an animal model of obesity, i.e., Wistar rats fed a high-fat diet (HFD) or standard rodent chow, and subsequently injected with CBD in a dose of 10 mg/kg or its solvent for two weeks. The sphingolipid content was assessed using high-performance liquid chromatography (HPLC), while, in order to determine insulin and glucose concentrations, immunoenzymatic and colorimetric methods were used. The protein expression from sphingolipid and insulin signaling pathways, as well as endocannabinoidome components, was evaluated by immunoblotting. Unexpectedly, our experimental model revealed that the significantly intensified intramuscular de novo CER synthesis pathway in the HFD group was attenuated by chronic CBD treatment. Additionally, due to CBD administration, the content of other sphingolipid derivatives, i.e., sphingosine-1-phosphate (S1P) was restored in the high-fat feeding state, which coincided with an improvement in skeletal muscle insulin signal transduction and glycogen recovery.

Analysis of platelets from a diet-induced obesity rat model: elucidating platelet dysfunction in obesity

Obesity is one of the main health problems in industrialized countries. The contribution of multiple factors developed in obesity can hardly be modeled in vitro. In this context, the development of animal models mimicking human obesity could be essential. The aim of the present study was to compare platelets from a diet-induced obesity (DIO) rat model with their lean control group in order to elucidate platelet dysfunction mechanisms in obesity and correlate the results with previous data from morbid obese patients. In parallel, we also established a blood collection and platelet isolation methodology to study the DIO rat model at biochemical and functional level. Optimal blood collection was obtained from vena cava and platelet isolation was based on a serial of centrifugations avoiding platelet activation. Our results show that the DIO rat model simulate obesity pathologically since weight gain, fasting glucose and platelet counts are increased in obese rats. Interestingly, platelet levels of the active form of Src (pTyr419) showed a tendency to increase in DIO rats pointing towards a potential dysfunction in Src family kinases-related signalling pathways in obesity. Moreover, platelets from DIO rats adhere more to collagen compared with the control group, pointing towards Glycoprotein VI (GPVI) as one of the dysregulated receptors in obesity, in agreement with our recent studies in humans. These results confirm that obesity, in line with human studies, present a platelet dysregulation, and highlight the relevance of considering novel antithrombotic drug targets in these patients, such as GPVI.

Differential Effects of Chronic Ingestion of Refined Sugars versus Natural Sweeteners on Insulin Resistance and Hepatic Steatosis in a Rat Model of Diet-Induced Obesity.

While the detrimental effect of refined sugars on health has been the subject of many investigations, little is known about the long-term impact of natural sweeteners on metabolic disorders. In this study we compared the metabolic responses to chronic ingestion of refined sugars compared to various natural sweeteners in diet-induced obese rats. Wistar rats were fed a high-fat high-sucrose diet (HFHS) for 8 weeks and daily gavaged with a solution containing 1 g of total carbohydrates from refined sugar (sucrose or fructose) or six different natural sugar sources, followed by assessment of glucose homeostasis, hepatic lipid accumulation, and inflammation. While glucose tolerance was similar following treatments with refined and natural sugars, lowered glucose-induced hyperinsulinemia was observed with fructose. Consumption of fructose and all-natural sweeteners but not corn syrup were associated with lower insulin resistance as revealed by reduced fasting insulin and homeostatic model assessment of insulin resistance (HOMA-IR) compared to sucrose treatment of HFHS-fed rats. All-natural sweeteners and fructose induced similar liver lipid accumulation as sucrose. Nevertheless, maple syrup, molasses, agave syrup, and corn syrup as well as fructose further reduced hepatic IL-1β levels compared to sucrose treatment. We conclude that natural sweeteners and especially maple syrup, molasses, and agave syrup attenuate the development of insulin resistance and hepatic inflammation compared to sucrose in diet-induced obese rats, suggesting that consumption of those natural sweeteners is a less harmful alternative to sucrose in the context of obesity.

646 - Prostatic enlargement and chronic inflammation in association with downregulation of SQSTM1/p62 in high fat diet induced obesity rat model

646 - Prostatic enlargement and chronic inflammation in association with downregulation of SQSTM1/p62 in high fat diet induced obesity rat model

Whole Egg Consumption Decreases Cumulative Weight Gain in Diet-Induced Obese Rats

Whole egg (WE) consumption has been demonstrated to attenuate body weight (BW) gain and adiposity in genetic animal models of type 2 diabetes (T2D). This finding was accompanied by increased food consumption. This study aimed to examine the effects of long-term WE intake on BW gain, fat distribution, and food intake in a rat model of diet-induced obesity (DIO). Male Sprague Dawley rats (n=24) were obtained at 5 wk of age and were randomly weight-matched across 1 of 4 dietary intervention groups (6 rats per group): a casein-based diet (CAS), a high-fat high-sucrose CAS diet (HFHS CAS), a whole egg-based diet (EGG), or a high-fat high-sucrose EGG diet (HFHS EGG). All diets provided 20% (w/w) protein and were provided for 33 wk. HFHS diets provided ∼61% of kilocalories from fat and 10% from sucrose. Daily weight gain and food intake were recorded, biochemical parameters were measured via ELISA, and epididymal fat pad weights were recorded at the end of the study. At 33 wk, cumulative BW gain in DIO rats fed HFHS EGG resulted in 23% lower weight gain compared with DIO rats fed HFHS CAS (P <0.0001), but no significant differences in BW gain were observed between the HFHS EGG group and the control EGG and CAS groups (P=0.71 and P=0.61, respectively). Relative food intake (grams per kilogram BW) was 23% lower (P<0.0001) in rats fed HFHS CAS compared with CAS, whereas there was no difference in food intake within the EGG dietary groups. DIO rats fed HFHS EGG exhibited a 22% decrease in epididymal fat weight compared with their counterparts fed the HFHS CAS. Our data demonstrate that consumption of a WE-based diet reduced BW gain and visceral fat in the DIO rat, similar to our previous findings in a genetic rat model with T2D.