High Fat Sugar Research Articles

Eight weeks consumption of high-fat diet promotes Mesenteric fat deposition when compared to other rat diets

Metabolic syndrome is a grouping of several medical conditions plaguing the modern world today. Excessive visceral fat is strongly associated with abdominal obesity which is one of the characteristics of metabolic syndrome. In general, an unbalanced, rich diet plays an important role in the proliferation of adipocytes. Our aim is to observe which diet contributes to the deposition of visceral fat such as the mesenteric fat. For eight weeks, thirty-five Sprague Dawley rats were divided into five groups and were fed five different types of diets. The five diets are normal rat chow, high sugar, high starch, high protein and high fat rat (palm oil-based) feed formula. Besides the formularized rat feeds, the rats were given tap water ad libitum. The result showed high fat diet promotes mesenteric fat proliferation when compared to other rat feed formula. Present study showed that high-fat diet promotes mesenteric fat proliferation when compared to other diets.

Resveratrol Blunts Mitochondrial Loss in Slow and Mixed Skeletal Muscle Phenotypes of Non-Human Primates following a Long-Term High Fat/Sugar Diet

Mitochondrial biogenesis and destruction in skeletal muscle are coordinated by distinct signaling pathways that are influenced by internal and exogenous variables including, but not limited to, muscle phenotype, physical activity, dietary composition, or drug administration. Previously we found that long-term resveratrol administration (up to 480 mg/day) ameliorates the slow-to-fast phenotypic shift in soleus muscles and promotes the expression in slow myosin heavy chain in the mixed plantaris muscle of non-human primates consuming a high fat/sugar (HFS) diet. Here, we expand on these earlier findings by examining whether mitochondrial content and the markers that dictate their biogenesis and mitophagy/autophagy are similarly affected by HFS and/or influenced by resveratrol while consuming this diet (HFSR). Compared to controls (n = 9), there was a ∼20–25% decrease in mitochondrial content in HFS (n = 8) muscles as reflected in the COX2- and CYTB-to-GAPDH ratios using PCR analysis, which was blunted by resveratrol in HFSR (n = 7) soleus and, to a lesser degree, in plantaris muscles. A ∼1.5 and 3-fold increase in Rev-erb-α protein was detected in HFSR soleus and plantaris muscles compared to controls, respectively. Unlike in HFSR animals, HFS soleus and plantaris muscles exhibited a ∼2-fold elevation in phosphor-AMPKα (Thr172). HFS soleus muscles had elevated phosphorylated-to-total TANK binding protein-1 (TBK1) ratio suggesting an enhancement in mito/autophagic events. Taken together, resveratrol appears to blunt mitochondrial losses with a high fat/sugar diet by tempering mito/autophagy rather than promoting mitochondrial biogenesis, suggesting that the quantity of daily resveratrol supplement ingested and/or its long-term consumption are important considerations. Supplemental data for this article is available online at http://dx.doi.org/ .

Mechanisms of liver injury in high fat sugar diet fed mice that lack hepatocyte X-box binding protein 1.

Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of liver diseases in the United States and can progress to cirrhosis, end-stage liver disease and need for liver transplantation. There are limited therapies for NAFLD, in part, due to incomplete understanding of the disease pathogenesis, which involves different cell populations in the liver. Endoplasmic reticulum stress and its adaptative unfolded protein response (UPR) signaling pathway have been implicated in the progression from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH). We have previously shown that mice lacking the UPR protein X-box binding protein 1 (XBP1) in the liver demonstrated enhanced liver injury and fibrosis in a high fat sugar (HFS) dietary model of NAFLD. In this study, to better understand the role of liver XBP1 in the pathobiology of NAFLD, we fed hepatocyte XBP1 deficient mice a HFS diet or chow and investigated UPR and other cell signaling pathways in hepatocytes, hepatic stellate cells and immune cells. We demonstrate that loss of XBP1 in hepatocytes increased inflammatory pathway expression and altered expression of the UPR signaling in hepatocytes and was associated with enhanced hepatic stellate cell activation after HFS feeding. We believe that a better understanding of liver cell-specific signaling in the pathogenesis of NASH may allow us to identify new therapeutic targets.

Prevalence and labelling characteristics of high fat sugar salt (HFSS) products in multibuy and entrance promotions in three UK supermarket websites

Prevalence and labelling characteristics of high fat sugar salt (HFSS) products in multibuy and entrance promotions in three UK supermarket websites

Acute Hypophagia and Changes in c-Fos Immunoreactivity in Adolescent Rats Treated with Low Doses of Oxytocin and Naltrexone.

A recent case report has shown that an adjunctive oxytocin + naltrexone (OT + NTX) treatment promoted more robust hypophagia and body weight reduction than OT alone in an adolescent male with hypothalamic obesity after craniopharyngioma resection. Thus far, there has been no basic research in adolescent laboratory animals that would examine whether the benefit of OT + NTX on appetite extends onto adolescent individuals without surgically induced overeating. Thus, here we examined whether low doses of combined OT + NTX acutely affect post-deprivation intake of energy-dense, standard chow; intake of energy-dense and palatable high-fat high-sugar (HFHS) diet; or calorie-dilute, palaTable 10% sucrose solution without deprivation in adolescent male rats. We assessed whether OT + NTX decreases water intake after water deprivation or produces a conditioned taste aversion (CTA). Finally, by using c-Fos immunoreactivity, we determined changes in activity of feeding-related brain areas after OT + NTX. We found that individual subthreshold doses of OT and NTX decreased feeding induced by energy and by palatability. Significant c-Fos changes were noted in the arcuate and dorsomedial hypothalamic nuclei. The hypophagic doses of OT + NTX did not suppress water intake in thirsty rats and did not cause a CTA, which suggests that feeding reduction is not a secondary effect of gastrointestinal discomfort or changes in thirst processing. We conclude that OT + NTX is an effective drug combination to reduce appetite in adolescent male rats.

Multi-Omics Comparison of the Spontaneous Diabetes Mellitus and Diet-Induced Prediabetic Macaque Models.

The prevalence of diabetes mellitus has been increasing for decades worldwide. To develop safe and potent therapeutics, animal models contribute a lot to the studies of the mechanisms underlying its pathogenesis. Dietary induction using is a well-accepted protocol in generating insulin resistance and diabetes models. In the present study, we reported the multi-omics profiling of the liver and sera from both peripheral blood and hepatic portal vein blood from Macaca fascicularis that spontaneously developed Type-2 diabetes mellitus with a chow diet (sDM). The other two groups of the monkeys fed with chow diet and high-fat high-sugar (HFHS) diet, respectively, were included for comparison. Analyses of various omics datasets revealed the alterations of high consistency. Between the sDM and HFHS monkeys, both the similar and unique alterations in the lipid metabolism have been demonstrated from metabolomic, transcriptomic, and proteomic data repeatedly. The comparison of the proteome and transcriptome confirmed the involvement of fatty acid binding protein 4 (FABP4) in the diet-induced pathogenesis of diabetes in macaques. Furthermore, the commonly changed genes between spontaneous diabetes and HFHS diet-induced prediabetes suggested that the alterations in the intra- and extracellular structural proteins and cell migration in the liver might mediate the HFHS diet induction of diabetes mellitus.

Mass Spectrometry-Based Metabolomic and Lipidomic Analysis of the Effect of High Fat/High Sugar Diet and GreenshellTM Mussel Feeding on Plasma of Ovariectomized Rats.

This study aimed to examine the changes in lipid and metabolite profiles of ovariectomized (OVX) rats with diet-induced metabolic syndrome-associated osteoarthritis (MetOA) after supplementation with greenshell mussel (GSM) using an untargeted liquid chromatography-mass spectrometry (LC-MS) metabolomics approach. Ninety-six rats were fed with one of four diets: control, control supplemented with GSM + GSM, high fat/high sugar (HFHS), or high fat/high sugar enriched with GSM (HFHS + GSM). After 8 weeks on experimental diets, half of the rats in each group underwent OVX and the other half were sham operated. After being fed for an additional 28 weeks, blood samples were collected for the metabolomics analysis. Lipid and polar metabolites were extracted from plasma and analysed by LC-MS. We identified 29 lipid species from four lipid subclasses (phosphatidylcholine, lysophosphatidylcholine, diacylglycerol, and triacylglycerol) and a set of eight metabolites involved in amino acid metabolism (serine, threonine, lysine, valine, histidine, pipecolic acid, 3-methylcytidine, and cholic acid) as potential biomarkers for the effect of HFHS diet and GSM supplementation. GSM incorporation more specifically in the control diet generated significant alterations in the levels of several lipids and metabolites. Further studies are required to validate these findings that identify potential biomarkers to follow OA progression and to monitor the impact of GSM supplementation.

Rice (Oryza sativa L.) bran preserves cardiac function by modulating pro-inflammatory cytokines and redox state in the myocardium from obese rats

PurposeThis study aimed to evaluate the effect of rice bran (RB) supplementation to a high-sugar fat (HSF) diet on cardiac dysfunction in an experimental obesity model.MethodsMale Wistar rats were distributed into three groups: control, high-sugar fat, and high-sugar fat supplemented with 11% RB for 20 weeks.ResultsHSF diet promoted obesity and metabolic complications. Obese rats showed cardiac structural and functional impairment associated with high levels of interleukin-6, tumoral necrosis factor alpha, and malondialdehyde, and decreased activity of superoxide dismutase and catalase in the myocardium. RB supplementation was able to mitigate obesity and its metabolic alterations in HSF diet-fed animals. Moreover, the RB also prevented structural and functional damage, inflammation, and redox imbalance in the heart of these animals.ConclusionThis study suggests that RB supplementation prevents cardiac dysfunction in rats fed on HSF by modulating systemic metabolic complications and inflammation and oxidative stress in the myocardium, representing potential alternative therapy.

O-155 Dietary caloric normalization or restriction as preconception care strategies: impact on oocyte developmental competence and quality in high fat/high sugar-induced obese outbred mice

Abstract Study question Can diet normalization or caloric restriction (CR) for two weeks be used as a preconception care intervention in obese Swiss mice to restore oocyte development and quality Summary answer Diet normalization or CR as short-term preconception care interventions in obese mice only partially restored oocyte quality but did improve overall developmental competence. What is known already Maternal metabolic disorders like obesity and metabolic syndrome may result in decreased oocyte and embryo quality, and thus reproductive failure. Overweight and obese patients are advised to lose weight before conception to increase the chance of a healthy pregnancy. However, as human studies show no univocal guidelines, more fundamental research might provide additional answers. In order to avoid interference with increased maternal age, the question remains if oocyte quality can be restored after only a short preconception care intervention (PCCI). Study design, size, duration Outbred mice were fed a control (CTRL) or high-fat/high-sugar (HF) diet for seven weeks. Afterwards, HF-mice were put on different PCCIs for two weeks, resulting in four treatment groups: control diet (9w; CTRL_CTRL), HF diet (9w; HF_HF), switch from HF (7w) to an ad libitum control diet for 2w (HF_CTRL) or to a 30% CR diet for 2w (HF_CR). Oocyte developmental competence (n = 357) and quality (12-16 oocytes /treatment, scored blinded) were determined, using 6-8 mice/treatment. Participants/materials, setting, methods Body weight changes were recorded. In vivo matured oocytes were collected after superovulation and analysed for quality or in vitro fertilized and cultured. Oocyte quality was determined by staining for lipid content (Bodipy) and mitochondrial inner membrane potential and active mitochondria localization (JC-1). Oocyte developmental competence [cleavage (24h p.i.) and blastocyst rates (5 days p.i.)] was scored. Categorical and numerical data were analysed using binary logistic regression and ANOVA, respectively and corrected for multiple testing. Main results and the role of chance Compared to the CTRL group, HF diet increased body weight after 7 weeks by 24.19% (P < 0.001). After the start of the PCCI, both HF_CTRL and HF_CR mice progressively lost weight and reached values similar to control mice after two weeks. HF_HF diet increased the intracellular lipid content in oocytes with 54.3% compared to the CTRL_CTRL group (P < 0.05). This increased content was (partially) normalized in both preconception care intervention groups, even similar to the control levels in the HF_CTRL group. Both HF_HF and HF_CR oocytes showed a tendency to an increased ratio of active/total mitochondria when compared to the CTRL_CTRL group (P = 0.081, P = 0.083 respectively). In addition, active oocyte mitochondria in the HF_HF group were less pericortically distributed compared to controls. This was also the case in both preconception care intervention groups (P < 0.05). After two weeks of PCCI, oocytes from HF_HF mice displayed lower cleavage rates than those from CTRL_CTRL mice (36.26% vs. 64.52%, P < 0.05) but blastocyst rates (26.37% vs. 35.48%, P > 0.1) were not different. HF_CR, but not HF_CTRL, oocytes showed higher cleavage rates (68.48%, P < 0.001) compared with HF_HF oocytes. Moreover, both HF_CTRL (44.64%, P < 0.05) and HF_CR (59.78%, P < 0.001) oocytes showed improved blastocyst rates when compared to the HF_HF group (26.37%). Limitations, reasons for caution Although using a mouse model has several advantages, translating these results to the human setting is a limitation of this study. However, to improve this translatability, an outbred mouse model was used. Additional data will be collected to gain more information regarding the best preconception care intervention advice. Wider implications of the findings This research aims to provide fundamental insights in order to be able to formulate clear preconception guidelines to obese women planning for pregnancy. In addition, we aim to find the shortest possible intervention period to improve fertility. Trial registration number Not applicable

L-Arginine Supplementation Significantly Affects Plasma Metabolome in Healthy Adults with Cardiometabolic Risk Irrespectively of Their Response to a Challenge Meal

Abstract Objectives We aimed to characterize the effects of a low dose of a sustained-release L-arginine (L-ARG) supplementation on plasma metabolome in healthy overweight adults with cardiometabolic risk factors, and study if its effect could improve the capacity to handle a high fat-high sugar meal, that deeply and acutely challenge metabolic capacities. Methods In a randomized, double-blind, controlled trial, 33 healthy overweight adults (BMI > 25kg/m²) with cardiometabolic risk (plasma triglycerides > 150 mg/dL; waist circumference > 94 cm (men) or > 80 cm (women)) were treated with 1.5 g L-ARG 3 times/d (4.5 g/d) or placebo for 4 weeks. On the last day of treatment, the volunteers consumed a high fat, high sugar meal challenge (900 kcal). Plasma was collected at fasting and 2, 4 and 6 h after the meal. Metabolites were analyzed by high-resolution mass spectrometry hyphenated to liquid chromatography, using reversed and normal phase columns, and operated in both positive and negative ionization modes. Annotation was performed using an in-house database referencing more than 1300 metabolites. Metabolic profiles were analyzed using Linear Mixed Models-PCA (LiMM-PCA), which enables to analyze repeated multivariate data. LiMM-PCA combines linear mixed models and PCA to assess the effects of both fixed factors (Treatment, Time before and after meal, interaction Treatment x Time, Order of treatment administration and Period of the study) and random factors (Individual). Results 521 metabolic features were identified in the plasma. Time accounted for most part of the variance in dataset (30.0%, P < 0.001), showing that the challenge meal leaved the largest imprint on the metabolome, with a clear distinction between fasting and fed states. In contrast, interindividual variability explained 10.1% of the total variance. L-ARG treatment significantly affected plasma metabolome (P < 0.001), explaining 0.6% of the variance. This effect did not differ after the challenge meal (time–treatment interaction, P > 0.10). The analysis of the metabolites contributing the most to these effects is under progress. Conclusions L-ARG supplementation has a significant effect on the metabolome in a situation where the metabolome is heavily impacted by a large allostatic load, and these two effects are independent of each other. Funding Sources Supported by a grant from Pierre Fabre Research Institute.

Effect of combination of peripheral oxytocin and naltrexone at subthreshold doses on food intake, body weight and feeding-related brain gene expression in male rats

In a recent case report involving a male with hypothalamic obesity, concurrent administration of oxytocin (OT) and an opioid receptor antagonist, naltrexone (NTX), synergistically affected energy balance. Here, by using laboratory rats, we examined whether the reported synergy between OT and NTX in the context of food intake extends beyond that one unique case. We found that intravenous OT+NTX combination, at doses subthreshold for each of the drugs individually, decreased episodic consumption of a 10% sucrose solution in non-deprived animals. Daily administration of OT and NTX just before a scheduled, 2-hour, high-fat high-sugar (HFHS) meal over 24 days, decreased cumulative HFHS diet intake, but without a change in body weight due to compensatory standard chow intake during the remainder of the day. The NTX-OT treatment affected expression of several feeding-related genes in the hypothalamus, brain stem and nucleus accumbens, brain regions essential for the regulation of energy- and reward-driven consumption. We conclude that OT and NTX act synergistically to decrease food consumption in rats and that this transient effect is accompanied by changes in brain processes relevant to feeding.

Anti-Inflammatory, Anti-Oxidant, and Anti-Lipaemic Effects of Daily Dietary Coenzyme-Q10 Supplement in a Mouse Model of Metabolic Syndrome.

The dietary model of metabolic syndrome has continued to aid our understanding of its pathogenesis and possible management interventions. However, despite progress in research, therapy continues to be challenging for humans; hence, the search for newer treatment and prevention options continues. The objective of this study was to evaluate the impact of dietary CQ10 supplementation on metabolic, oxidative, and inflammatory markers in a diet-induced mouse model of metabolic syndrome. Mouse groups were fed a Standard Diet (SD), High-Fat High-Sugar (HFHS) diet, and SD or HFHS diet (with incorporated CQ10) at 60 and 120 mg/kg of feed. At the completion of the study (8 weeks), blood glucose levels, Superoxide Dismutase (SOD) activity, plasma insulin, leptin, adiponectin, TNF-α, IL-10, serum lipid profile, and Lipid Peroxidation (LPO) levels were assessed. The liver was either homogenised for the assessment of antioxidant status or processed for general histology. Dietary CQ10 mitigated HFHS diet-induced weight gain, decreased glucose, insulin, and leptin levels, and increased adiponectin levels in mice. Coenzyme-Q10 improved the antioxidant status of the liver and blood in HFHS diet-fed mice while also decreasing lipid peroxidation. Lipid profile improved, level of TNF-α decreased, and IL-10 increased following CQ10 diet. A mitigation of HFHS diet-induced alteration in liver morphology was also observed with CQ10. Dietary CQ10 supplementation mitigates HFHS diet-induced changes in mice, possibly through its anti-oxidant, anti-lipaemic, and anti-inflammatory potential.

The cost of eating more sustainable diets: A nutritional and environmental diet optimisation study

ABSTRACT We aim to identify the dietary changes to improve nutrition and reduce diet-related greenhouse gas emission (GHGE) simultaneously in Brazil, taking into account the heterogeneity in food habits and prices across the country. Food consumption and prices were obtained from two nationwide surveys (n = 55,970 households and 34,003 individuals). Linear programming models were performed to design optimised diets most resembling the observed diets, and meeting different sets of constraints: (i) nutritional, for preventing chronic diseases and meeting nutrient adequacy; (ii) socio-cultural: by respecting food preferences; and (iii) environmental: by reducing GHGE by steps of 10%. Moving toward a diet that meets nutritional recommendations led to a 14% to 24% cost increase and 10% to 27% GHGE reduction, depending on the stringency of the acceptability constraints. Stronger GHGE reductions were achievable (up to about 70%), with greater departure from the current diet, but not achieving calcium and potassium goals. Diet cost increment tended to be mitigated with GHGE reduction in most models, along with reductions in red meat, chicken, eggs, rice, and high-fat sugar sodium foods.

Pain in the Developing Brain: Early Life Factors Alter Nociception and Neurobiological Function in Adolescent Rats.

Although adverse early experiences prime individuals to be at increased risk for chronic pain, little research has examined the trauma–pain relationship in early life or the underlying mechanisms that drive pathology over time. Given that early experiences can potentiate the nociceptive response, this study aimed to examine the effects of a high-fat, high-sugar (HFHS) diet and early life stress (maternal separation [MS]) on pain outcomes in male and female adolescent rats. Half of the rats also underwent a plantar-incision surgery to investigate how the pain system responded to a mildly painful stimuli in adolescence. Compared with controls, animals that were on the HFHS diet, experienced MS, or had exposure to both, exhibited increased anxiety-like behavior and altered thermal and mechanical nociception at baseline and following the surgery. Advanced magnetic resonance imaging demonstrated that the HFHS diet and MS altered the maturation of the brain, leading to changes in brain volume and diffusivity within the anterior cingulate, amygdala, corpus callosum, nucleus accumbens, and thalamus, while also modifying the integrity of the corticospinal tracts. The effects of MS and HFHS diet were often cumulative, producing exacerbated pain sensitivity and increased neurobiological change. As early experiences are modifiable, understanding their role in pain may provide targets for early intervention/prevention.

Inhibition of PAI-1 Promotes Lipolysis and Enhances Weight Loss in Obese Mice.

This study investigates the therapeutic potential of a small molecule inhibitor of plasminogen activator inhibitor-1 (PAI-1), TM5441, in reversing diet-induced obesity in mice. Wild-type C57BL/6J mice were fed a high-fat high-sugar (HFHS) diet for 8 weeks to induce obesity. After the first 8 weeks, TM5441 was added to the diet for an additional 8 weeks. In order to determine the efficacy of PAI-1 inhibition in conjunction with dietary modification, mice were fed an HFHS diet for 8 weeks to induce obesity and were then switched to a low-fat diet with or without TM5441 for an additional 2 to 8 weeks. Obese mice showed weight reduction and significant improvement in hepatic steatosis when TM5441 was added to the HFHS diet. Obese mice that were treated with TM5441 in conjunction with dietary modification showed enhanced weight loss and a more rapid reversal of hepatic steatosis compared with obese mice treated with dietary modification alone. The enhanced weight loss among mice treated with TM5441 was associated with increased adipose tissue expression of adipose triglyceride lipase, phosphorylated hormone-sensitive lipase, and phosphorylated perilipin-1 as well as induction of adipose tissue lipolysis. Pharmacologic PAI-1 inhibition stimulates adipose tissue lipolysis and enhances weight loss in obese mice.

Protective Effects of Iridoid Glycoside from Corni Fructus on Type 2 Diabetes with Nonalcoholic Fatty Liver in Mice.

Type 2 diabetes mellitus (T2DM) is a common chronic metabolic disease. Accumulating evidence has demonstrated that nonalcoholic fatty liver disease (NAFLD) shares common typical features with T2DM, and they affect each other extensively. Thus, NAFLD has emerged as a novel target for T2DM prevention and care. Although Corni Fructus (CF) and its extracts have a therapeutic effect on T2DM, its effects and mechanisms on T2DM with NAFLD are far from elucidated. In this study, a mouse model of T2DM with NAFLD complication was established in ICR mice by feeding a high-fat, high-sugar (HFHS) diet and intraperitoneally injecting with a low dose of streptozotocin (STZ). Then, the effects of iridoid glycosides (IG) extracted from CF on this mouse model were investigated. We found that 4-week IG administration remarkably alleviated hyperglycemia and insulin resistance and significantly reduced inflammation, oxidative stress, and fat accumulation in the liver of T2DM with NAFLD mice. Further studies showed that IG inhibited the NF-κB but enhanced the PI3K-AKT signaling pathway. In summary, these results indicated that the IG from CF has potential therapeutic effects on T2DM with NAFLD.

Phenolic compounds from jaboticaba (Plinia jaboticaba (Vell.) Berg) ameliorate intestinal inflammation and associated endotoxemia in obesity

Jaboticaba (Plinia jaboticaba (Vell.) Berg) is a Brazilian native fruit belonging to the Myrtaceae family. Previously it was demonstrated that phenolic-rich extracts from jaboticaba (PEJ) possess health-beneficial properties in diet-induced obesity; however, whether PEJ modulates the obesity-associated intestinal inflammatory status remains unclear. Thus, male C57BL/6J obese mice were fed a high-fat-sugar (HFS) diet and received PEJ at two doses, 50 mg gallic acid equivalent (GAE)/kg body weight (BW) (PEJ1 group), and 100 mg GAE/kg BW (PEJ2 group), or water (HFS group) by oral gavage for 14 weeks. PEJ groups presented a reduced body weight gain and adiposity and were protected against insulin resistance and dyslipidemia. In addition, PEJ prevented metabolic endotoxemia linked to an attenuation of the HFS diet-induced intestinal inflammation via down-regulation of pro-inflammatory mediators such as tumor necrosis factor (TNF-α), membrane transporter toll-like receptor-4 (TLR-4) and nuclear factor-κB (NF-κB) in the colon. These anti-inflammatory effects appear to be involved, at least in part, with an inhibition of the colonic inflammasome pathway of obese mice.

COX-2 promotes mammary adipose tissue inflammation, local estrogen biosynthesis, and carcinogenesis in high-sugar/fat diet treated mice.

Obesity is a major risk factor for breast cancer, especially in post-menopausal women. In the breast tissue of obese women, cyclooxygenase-2 (COX-2)-dependent prostaglandin E2 (PGE2) production has been correlated with inflammation and local estrogen biosynthesis via aromatase. Using a mouse model of 7,12-dimethylbenz[a]anthracene/medroxyprogesterone-acetate (DMBA/MPA)-induced carcinogenesis, we demonstrated that an obesogenic diet promotes mammary tissue inflammation and local estrogen production, and accelerates mammary tumor formation in a COX-2-dependent manner. High-sugar/fat (HSF) diet augmented the levels of the pro-inflammatory mediators MCP-1, IL-6, COX-2, and PGE2 in mammary tissue, and this was accompanied by crown-like structures of breast (CLS-B) formation and aromatase/estrogen upregulation. Treatment with a COX-2 selective inhibitor, etoricoxib, decreased PGE2, IL-6, MCP-1, and CLS-B formation as well as reduced aromatase protein and estrogen levels in the mammary tissue of mice fed a HSF diet. Etoricoxib-treated mice showed increased latency and decreased incidence of mammary tumors, which resulted in prolonged animal survival when compared to HSF diet alone. Inhibition of tumor angiogenesis also seemed to account for the prolonged survival of COX-2 inhibitor-treated animals. In conclusion, obesogenic diet-induced COX-2 is sufficient to trigger inflammation, local estrogen biosynthesis, and mammary tumorigenesis.

English

High fat high sugar (HFHS) diet results in various disorders including oxidative stress. In present study, prebiotics supplementation was given to rats following HFHS diet feeding. The results showed that prebiotics significantly lowered the HFHS-diet associated elevated levels of cholesterol, triglyceride, low density lipids, alkaline phosphatase, blood urea, creatinine, uric acid and total proteins. Prebiotics significantly restored the HFHS-diet induced decrease in total anti-oxidant capacity. The levels of alanine aminotransferase, aspartate aminotransferase, bilirubin, total oxidation status, malondialdehyde, paraoxonase and arylesterase were not significantly different in HFHS-Prebiotics group as compared to control group. Histological analyses of liver, intestine and kidney tissues in HFHS-group showed cytoplasmic vacuolation, mucosal damage, hepatic triad abnormalities, eccentric nuclei, focal necrosis, tubular congestion and neutrophil infiltration which were significantly improved in HFHS+Prebiotics group suggesting ameliorative potential of prebiotics. In conclusion, our results demonstrated that prebiotics possess therapeutic potential in ameliorating HFHS-diet associated alterations in metabolic profile, oxidative stress markers and histological architecture in intestine, liver and kidney tissues

Metaplasticity in the Ventral Pallidum as a Potential Marker for the Propensity to Gain Weight in Chronic High-Calorie Diet.

A major driver of obesity is the increasing palatability of processed foods. Although reward circuits promote the consumption of palatable food, their involvement in obesity remains unclear. The ventral pallidum (VP) is a key hub in the reward system that encodes the hedonic aspects of palatable food consumption and participates in various proposed feeding circuits. However, there is still no evidence for its involvement in developing diet-induced obesity. Here we examine, using male C57BL6/J mice and patch-clamp electrophysiology, how chronic high-fat high-sugar (HFHS) diet changes the physiology of the VP and whether mice that gain the most weight differ in their VP physiology from others. We found that 10-12 weeks of HFHS diet hyperpolarized and decreased the firing rate of VP neurons without a major change in synaptic inhibitory input. Within the HFHS group, the top 33% weight gainers (WGs) had a more hyperpolarized VP with longer latency to fire action potentials on depolarization compared with bottom 33% of weight gainers (i.e., non-weight gainers). WGs also showed synaptic potentiation of inhibitory inputs both at the millisecond and minute ranges. Moreover, we found that the tendency to potentiate the inhibitory inputs to the VP might exist in overeating mice even before exposure to HFHS, thus making it a potential property of being an overeater. These data point to the VP as a critical player in obesity and suggest that hyperpolarized membrane potential of, and potentiated inhibitory inputs to, VP neurons may play a significant role in promoting the overeating of palatable food.SIGNIFICANCE STATEMENT In modern world, where highly palatable food is readily available, overeating is often driven by motivational, rather than metabolic, needs. It is thus conceivable that reward circuits differ between obese and normal-weight individuals. But is such difference, if it exists, innate or does it develop with overeating? Here we reveal synaptic properties in the ventral pallidum, a central hub of reward circuits, that differ between mice that gain the most and the least weight when given unlimited access to highly palatable food. We show that these synaptic differences also exist without exposure to palatable food, potentially making them innate properties that render some more susceptible than others to overeat. Thus, the propensity to overeat may have a strong innate component embedded in reward circuits.