Influence Of High-fat Diet Research Articles

Perspectives on obesity imaging: [18F]2FNQ1P a specific 5-HT6 brain PET radiotracer.

Estimates suggest that approximatively 25% of the world population will be overweight in 2025. Better understanding of the pathophysiology of obesity will help to develop future therapeutics. Serotonin subtype 6 receptors (5-HT6) have been shown to be critically involved in appetite reduction and weight loss. However, it is not known if the pathological cascade triggered by obesity modifies the density of 5-HT6 receptors in the brain. Influence of diet-induced obesity (DIO) in Wistar rats was explored using MRI (whole-body fat) and PET ([18F]2FNQ1P as a specific 5-HT6 radiotracer). The primary goal was to monitor the 5-HT6 receptor density before and after a 10-week diet (DIO group). The secondary goal was to compare 5-HT6 receptor densities between DIO group, Wistar control diet group, Zucker rats (with genetic obesity) and Zucker lean strain rats. Wistar rats fed with high-fat diet showed higher body fat gain than Wistar control diet rats on MRI. [18F]2FNQ1P PET analysis highlighted significant clusters of voxels (located in hippocampus, striatum, cingulate, temporal cortex and brainstem) with increased binding after high-fat diet (p < 0.05, FWE corrected). This study sheds a new light on the influence of high-fat diet on 5-HT6 receptors. This study also positions [18F]2FNQ1P PET as an innovative tool to explore neuronal consequences of obesity or eating disorder pathophysiology.

Abstract 2187: Influences of high-fat diet on tumor biology in a mouse model of colorectal cancer

Abstract Purpose: To test the influence of high-fat diet on tumor biology in the inducible Kras, Apc and p53 (iKAP) model (Boutin, et al Genes &amp; Development 2017, 31:370). Methods: At weening, both male and female mice were fed either a high-fat (60%) or low-fat (10%) diet for 5-6 weeks prior to tumor induction. Mutant Kras expression was controlled using a tet-on system. Expression of mutant Kras was activated by the addition of doxycycline hyclate in the drinking water. Tumor growth was monitored by bi-weekly endoscopy and calculated as percent luminal occlusion. Tumor biology was assessed with proteomics and phospho-proteomics with comparisons by sex and diet. Results: In the absence of mutant Kras expression (no doxycycline in drinking water), tumors were larger in females on high-fat diet compared to low-fat diet. Tumor sizes were not significantly different in males or in the presence of mutant Kras expression. Proteomics analyses of tumor tissue identified significantly different patterns by diet in female mice, including altered levels of KIF4, DAB2iP, JNK cascade and JUN kinase activity (Table). Conclusion: Based on our preliminary data, high-fat diet may alter tumor kinase activities, even in a genetically engineered mouse model. Replication and validation studies are ongoing. Table of significantly upregulated biologic processes in female mice on high-fat diet compared to lo XXXXXXXXXXXXXXXX XXXXXXXXXXXXXXX Citation Format: Anindita Mahanty, Cara Wallingford, Revan Hammontree, Muturi Njoka, Zachary Clark, Michaella Rekowski, Michael Washburn, Jennifer S. Davis. Influences of high-fat diet on tumor biology in a mouse model of colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2187.

Effect of High Fat Diet on Disease Development of Polycystic Ovary Syndrome and Lifestyle Intervention Strategies.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder that affects premenopausal women. The etiology of PCOS is multifaceted, involving various genetic and epigenetic factors, hypothalamic-pituitary-ovarian dysfunction, androgen excess, insulin resistance, and adipose-related mechanisms. High-fat diets (HFDs) has been linked to the development of metabolic disorders and weight gain, exacerbating obesity and impairing the function of the hypothalamic-pituitary-ovarian axis. This results in increased insulin resistance, hyperinsulinemia, and the release of inflammatory adipokines, leading to heightened fat synthesis and reduced fat breakdown, thereby worsening the metabolic and reproductive consequences of PCOS. Effective management of PCOS requires lifestyle interventions such as dietary modifications, weight loss, physical activity, and psychological well-being, as well as medical or surgical interventions in some cases. This article systematically examines the pathological basis of PCOS and the influence of HFDs on its development, with the aim of raising awareness of the connection between diet and reproductive health, providing a robust approach to lifestyle interventions, and serving as a reference for the development of targeted drug treatments.

Effects of Lecithin Supplementation in Feed of Different fat Levels on Serum Indexes and Liver Health of Laying Hens.

The aim of this experiment was to investigate the effect of soy lecithin on serum-related indicators and liver health in laying hens under the influence of high-fat diets. 180 peak laying hens at 40 weeks of age were randomly assigned to one of the four diets using a 2 × 2 factorial and fed for 5 weeks. The results showed that compared to the low-fat group, the high-fat group had lower egg production (p < 0.05) and higher average daily feed intake and feed-to-egg ratio (p < 0.05). At the 21st day, the serum levels of triglyceride (TC) and superoxide dismutase (SOD) were higher (p < 0.05), high-density lipoproteins cholesterol (HDL-C) levels were lower (p < 0.01), catalase (CAT) activity was lower (p < 0.05), TC and malondialdehyde (MDA) levels in liver were higher (p < 0.01) and SOD activity in liver was lower (p < 0.05) in layers supplemented with soy lecithin. CAT activity in serum was increased (p < 0.01) and total antioxidant capacity (T-AOC) activity in the liver was decreased (p < 0.05) after increasing the dietary fat concentration. The addition of soy lecithin and the increase in dietary fat concentration had a highly significant interaction on serum CAT activity and liver TC content in layers (p < 0.01). At the 35th day, the serum alanine aminotransferase (ALT) activity was higher (p < 0.01), serum glutathione peroxidase (GSH-Px) and CAT activity were higher (p < 0.05), and serum triglyceride (TG) content and total T-AOC capacity activity were lower (p < 0.05) in layers supplemented with soy lecithin. Increasing dietary fat concentration decreased alanine aminotransferase (ALT), aspartate aminotransferase (AST) and GSH-Px activity in serum (p < 0.05). However, it increased TG and MDA content in liver (p < 0.05), and highly decreased SOD content in liver (p < 0.01) in layers. The addition of soy lecithin and increasing dietary fat concentration had a highly significant reciprocal effect on serum ALT viability and CAT viability (p < 0.01) and liver TG and MDA content and SOD viability (p < 0.05) in layers. In conclusion, feeding high-fat diets will adversely affect the laying performance of laying hens, while long-term addition of lecithin can improve the blood lipids and liver lipids of laying hens, enhance the antioxidant capacity of the liver, and maintain liver health.

Targeted profiling of rodent unconjugated bile acids using GC-MS to determine the influence of high-fat diet.

Unconjugated bile acids (BAs) have gained more attention than conjugated BAs in the association studies among diet, gut microbiota, and diseases. GC-MS is probably a good choice for specialized analysis of unconjugated BAs due to its high separation capacity and identification convenience. However, few reports have focused on the rodent unconjugated BAs using GC-MS, and the main library for identification has not included rodent-specific BAs. We developed a GC-MS method for targeted profiling of eight main unconjugated BAs in rodent models, which showed excellent performance on sensitivity, reproducibility, and accuracy. Quantitative reproducibility in terms of relative standard deviation (RSD) was in the range of 2.05-2.91%, with detection limits of 3-55 ng/mL, quantitation limits of 9-182 ng/mL, and the recovery rate of 72-115%. All the calibration curves displayed good linearity with correlation coefficient values (R2 ) more than 0.99. Using the established method, the influence of high-fat diet on the metabolism of unconjugated BAs was revealed. Significant increase in fecal unconjugated BAs induced by high-fat diet would be a potential risk to gut inflammation and cancer. The study provides a convenient and targeted GC-MS method for specialized profiling of rodent unconjugated BAs in physiological and pathological studies.

Mapping the global research landscape on nutrition and the gut microbiota: Visualization and bibliometric analysis.

BACKGROUNDNutrition is a significant modifiable element that influences the composition of the gastrointestinal microbiota, implying the possibility of therapeutic diet methods that manipulate the composition and diversity of the microbial.AIMTo overview research papers on nutrition and gut microbiota and determines the hotspots in this field at the global level.METHODSScopus and Reference Citation Analysis were used to construct a bibliometric technique. It was decided to create bibliometric indicators and mapping as in most previous studies. 2012 through 2021 served as the study's timeframe.RESULTSA total of 5378 documents from the Scopus database were selected for analysis. Of all retrieved studies, 78.52% were research papers (n = 4223), followed by reviews (n = 820; 15.25%). China ranked first with a total number of articles of 1634 (30.38%), followed by the United States in second place with a total number of articles of 1307 (24.3%). In the last decade, emerging hotspots for gut microbiota and nutrition research included "gut microbiota metabolism and interaction with dietary components", "connection between the gut microbiota and weight gain", and "the influence of high-fat diet and gut microbiota on metabolic disorders".CONCLUSIONThis is the first thorough bibliometric analysis of nutrition and gut microbiota publications conducted on a global level. Investigation of the association between nutrition/diet and the gut microbiota is still in its infancy and will be expanded in the future. However, according to recent trends, the “effect of gut microbiota and high-fat diet on metabolic disorders" will be an increasing concern in the future.

GABAA δ receptors in vagal motor neurons play a role in the influence of high fat diet on cardiac function

Central vagal circuitry plays a key role in cardioinhibition and is critical to cardiac homeostasis. Long‐term high fat diet (HFD) is associated with decreased vagal drive, which is linked to increased cardiovascular morbidity and mortality. However, recent evidence suggests that HFD elicits changes in central circuits during early consumption (days). This study tested the hypothesis that decreased central vagal regulation contributes to poor cardiac regulation during the first two weeks of HFD. C57/Bl6 mice were examined for changes in autonomic regulation of HR both at rest and during reflex challenges using chronically implanted telemetry devices. Metabolic parameters were examined throughout all experiments. HFD fed mice exhibited a resting tachycardia throughout the two weeks of HFD (669 ± 20 bpm) compared to NFD (606 ± 20 bpm; p=0.03). Using pharmacological manipulations at Day 15, animals given HFD showed lower resting HR responses to intraperitoneal injection of the parasympathetic antagonist, methyl‐scopolamine, (68 ± 8 bpm) compared to NFD (104 ± 15 bpm; p=0.03). To determine if HFD also influenced homeostatic regulation of HR, animals were tested for capsaicin‐ and phenylbiguanide (PBG)‐mediated cardiopulmonary reflexes. In these animals, HFD blunted capsaicin‐mediated cardiopulmonary reflex at day 15 of HFD (‐19 ± 7 bpm), compared to NFD (‐45 ± 3 bpm; p=0.01). The HFD‐induced blunting of capsaicin‐mediated bradycardia continued throughout testing (60 days; ‐22 ± 5 bpm in HFD). No changes were seen in PBG‐mediated bradycardias (p=0.86). Previous work from our lab indicates that vagal motor neurons after metabolic challenges express large GABAergic currents mediated by GABAA receptors expressing the δ‐subunit, GABAA(δ)R. Since GABAergic neurotransmission is critical to both resting HR and reflex responses, we generated a novel bi‐transgenic mouse line using a floxed GABAA(δ)R and ChATcre mouse line (ChAT‐ δnull) to knock out the expression of δ‐subunit in vagal motor neurons. Examination of resting HR after HFD and NFD in ChAT‐ δnull showed no differences between diets (p=0.68). Pharmacological manipulations of HR in ChAT‐δnull mice with methyl‐scopolamine also showed no differences in HR responses between the diets (p=0.34). In addition, ChAT‐ δnull mice on HFD (61 ± 9 bpm) no longer showed a significant blunting of capsaicin‐mediated bradycardia compared to NFD (39 ± 5 bpm; p=0.10). Together, this study showed that HFD induces lasting changes in central circuitry within 15 days after consumption. In addition, this study found that parasympathetic dysfunction contributes to early HFD‐induced changes in HR and autonomic reflexes. This is important, as most pharmaceutical treatments currently available to patients target the sympathetic hyperactivity, and not parasympathetic hypoactivity. Finally, increased GABAA(δ)Rs likely mediate decreased vagal output after HFD. Therefore, more research is needed to determine mechanistic underpinning(s) of increased GABAA(δ)R activity and parasympathetic dysfunction to lead to better treatment options for cardiovascular disease associated with high fat diet consumption.

The influence of high fat diet on gut dysbiosis and myocardial function.

The influence of high fat diet on gut dysbiosis and myocardial function.

Influence of high-fat diet on host animal health via bile acid metabolism and benefits of oral-fed Streptococcus thermophilus MN-ZLW-002.

In this study, C57BL/6J male mice were fed normal chow (NC; control) or a high-fat diet (HFD) for 12 weeks, and HFD mice were supplemented with oral administration of Streptococcus thermophilus MN-ZLW-002 (HFD + MN002); n=20/group. Body weight, visceral fat, blood glucose, blood lipids and liver lipid deposition increased in the HFD group, and the composition of gut microbiota, cecum short-chain fatty acids and fecal bile acids (BAs) also changed. Oral-fed MN-002 increased the relative abundances of Ruminococcaceae, Lachnospiraceae and Streptococcaceae and improved blood glucose, liver cholesterol deposition, and serum IL-10, CCL-3 and the fecal BAs composition. In conclusion, the high-fat diet changed the composition of bile acids by shaping the gut microbiota into an obese type, leading to metabolic disturbances. Streptococcus thermophilus MN-ZLW-002 regulated gut microbiota by adjusting the composition of bile acids and improved the perturbation caused by high-fat diets. However, the effect of MN002 observed in animal experiments needs to be verified by long-term clinical trials.

A high extra-virgin olive oil diet induces changes in metabolic pathways of experimental mammary tumors

Breast cancer is the most common malignancy in women worldwide, and environmental factors, especially diet, have a role in the etiology of this disease. This work aimed to investigate the influence of high fat diets (rich in corn oil or extra virgin olive oil -EVOO-) and the timing of dietary intervention (from weaning or after induction) on tumor metabolism in a seven,12-dimethylbenz[a]anthracene (DMBA)-induced breast cancer model in rat. The effects of lipids (oils and fatty acids) have also been investigated in MCF-7 cells. The results have confirmed different effects on tumor progression depending on the type of lipid. Molecular analysis at mRNA, protein and activity level of enzymes of the main metabolic pathways have also shown differences among groups. Thus, the animals fed with the EVOO-enriched diet developed tumors with less degree of clinical and morphological malignancy and showed modified glucose and mitochondrial metabolism when compared to the animals fed with the corn oil-enriched diet. Paradoxically, no clear influence on lipid metabolism by the high fat diets was observed. Considering previous studies on proliferation and apoptosis in the same samples, the results suggest that metabolic changes have a role in the molecular context that results in the modulation of different signaling pathways. Moreover, metabolic characteristics, without the context of other pathways, may not reflect tumor malignancy. The time of dietary intervention plays also a role, suggesting the importance of metabolic plasticity and the relation with mammary gland status when the tumor is induced.

1953-P: Influence of High-Fat Diet on Adipokine, Leptin, Betatrophin, and PTX3 in Obese Sprague-Dawley Rats Undergoing Metabolic Surgery

Introduction: High-fat diet (HFD) leads to obesity which causes low grade inflammation and changes in adipokines and hepatokines. Metabolic surgery, like ileal transposition (IT) leads to beneficial metabolic effect and lowers inflammatory state. However these positive effects diminish with time and data related to dietary factors modifying these effects are scare. Aim: To assess influence of HFD on plasma adiponectin, leptin, betatrophin and pentraxin 3 (PTX3) in obese rats undergoing metabolic surgery. Methods: There were 24 rats fed for 8 weeks with HFD to induce obesity. After 8 weeks half of them underwent IT and half of them SHAM surgery. For 8 weeks after surgery half of the rats in the IT and in the SHAM group were fed with HFD and half of them with control diet (CD). After 8 weeks following surgery adipokines namely adiponectin and leptin as well as hepatokine namely betatrophin and inflammatory protein PTX3 were assessed. Outcomes: When comparing HFD to CD groups following two surgery procedures rats who underwent IT comparing to SHAM surgery had significantly higher concentration of betatrophin (1751.2 vs 594.5 pg/ml; P=0.0041) when continued to be fed with HFD as well as when the diet was changed to CD (2391.2 vs 922.9 pg/ml; P=0.0047) and significantly higher concentration of adiponectin (72.6 vs 28.7 ng/ml; P=0.007) only among those rats who continued to be fad with HFD. There was higher concentration of betatrophin observed among rats who were postoperatively fed with HFD comparing to rats who were fed with CD in the IT surgery group but the difference was not significant (2301.2 vs 1751.2 pg/ml; P= 0.0552). There was no difference in PTX3 and leptin observed among IT compared to SHAM operated animals in relation to diet. Conclusion: The study indicates that diet may modify the effects of metabolic surgery on adiponectin and betatrophin which are hormones influencing metabolic state and this may serve as a motivation to investigate this phenomenon in humans. Disclosure K. Nabrdalik: None. T. Sawczyn: None. D.M. Stygar: None. J. Gumprecht: Consultant; Self; Astra, Bioton, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck &amp; Co., Inc., Merck Sharp &amp; Dohme Corp., Mundipharma International, Novo Nordisk A/S, Polfa Tarchomin S.A., Sanofi, Servier. Speaker’s Bureau; Self; Astra, Bioton, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck &amp; Co., Inc., Merck Sharp &amp; Dohme Corp., Mundipharma International, Novo Nordisk A/S, Polfa Tarchomin S.A., Sanofi, Servier.

2285-PUB: Hippocampal Transcriptomic Changes Due to High-Fat Diet in Prediabetic Mice

The metabolic syndrome, prediabetes, and type 2 diabetes are increasingly common conditions worldwide, which predispose patients to the development of significant complications in both the central and peripheral nervous systems. Recently, our integrated lipidomics and transcriptomics study revealed an important role for lipid signaling pathways in peripheral nerves of mouse models of prediabetes and type 2 diabetes. While these data point to possible mechanisms of nerve damage peripherally, less is known about damage due to prediabetes and diabetes in the brain. This is of particular interest as growing evidence indicates that these conditions negatively affect cognition. Therefore, we performed RNA-Seq on hippocampi, a major site of learning and memory in the brain. Samples were isolated from a model of prediabetes and cognitive decline, wherein mice are fed a 60% high-fat diet (HFD). We identified various differentially expressed genes (DEGs) due to HFD, particularly after 11 wks (n=886), with fewer after 19 wks (n=111). Pathway analysis showed enrichment of pathways previously identified in the peripheral nervous system in response to HFD, including inflammatory and MAPK signaling pathways. Of interest, ∼31% of DEGs due to 11 wks of HFD overlapped with DEGs due to age (control animals only, comparing 19 to 11 wks of diet). These overlapping DEGs included genes such as fatty acid elongase 6 and hyccin (leukodystrophy protein FAM126A), which have roles in lipid metabolism and myelination, respectively. Enrichment analysis revealed multiple metabolic and protein processing pathways, such as oxidative phosphorylation and the proteasome. These data suggest that, like the peripheral nervous system, HFD effects similar pathways in the brain and may accelerate age-related gene expression changes in the hippocampus. However, more robust studies are needed to fully understand the influence of HFD on possible premature brain aging and how gene expression changes may contribute to cognitive decline. Disclosure S. Elzinga: None. R. Henn: None. P.D. O’Brien: None. K. Guo: None. S. Eid: None. A.E. Rumora: None. L.M. Hinder: None. J.M. Hayes: None. F. Mendelson: None. E.L. Feldman: Consultant; Self; Novartis Pharmaceuticals Corporation. J. Hur: None. Funding Program for Neurology Research and Discovery (T32DK007245, T32DK101357); National Institutes of Health (R24DK082841)

Chia Seed Oil Prevents High Fat Diet Induced Hyperlipidemia and Oxidative Stress in Mice

AbstractHyperlipidemia is a common cardiovascular disease. At present, the influence of high fat diet (HFD) on this is being explored. Recently, vegetable oils rich in omega‐3 have been reported that can treat hyperlipidemia caused by HFD. However, the effects of chia seed oil (CSO) on HFD‐induced hyperlipidemia and oxidative stress are poorly studied. Hence, in this study, the effects of CSO on hyperlipidemia and oxidative stress induced by HFD in mice are analyzed by various commercial kits, section staining, and protein expression. The results show that CSO decreases body weight and organ index. Meanwhile, CSO reduces serum lipid levels of total cholesterol, triglyceride, and low‐density lipoprotein cholesterol. It can also elevate superoxide dismutase and glutathione peroxidase activities and reduce malondialdehyde content in serum and liver. The results of histopathological analysis prove that CSO improves hepatic steatosis and reduces lipid deposition. Further, the results of western blot demonstrate that CSO upregulates the expression of peroxisome proliferator‐activated receptor alpha and carnitine palmitoyltransferase 1a in the liver. As a result, CSO may be a potential lipid‐lowering oil to prevent and treat HFD‐induced hyperlipidemia and oxidative stress.Practical Applications CSO, as a byproduct of chia seed processing, is a rich source of α‐linolenic acid. This study investigates the effects of CSO on HFD‐induced hyperlipidemia and oxidative stress in mice. It is concluded that dietary CSO can improve the hyperlipidemia in HFD‐induced mice via analysis of lipid parameters, histopathology study of the liver, and lipid metabolism related genes. In addition, supplementation of CSO also can improve the oxidative stress in mice. Therefore, CSO can be used for the prevention of hyperlipidemia and oxidative stress. This research provides a theoretical basis for the comprehensive development and utilization of functional chia seed oil.

The influence of high fat diet on plasma incretins and insulin concentrations in Sprague-Dawley rats with diet-induced obesity and glucose intolerance undergoing ileal transposition

BackgroundThe benefits of IT surgery are based on incretin effects. In this study we show the influence of high fat diet (HFD) used both before and after surgery, on ileal transposition (IT) effects. MethodsForty-eight male rats were assigned to two groups: HFD and control diet (CD) fed rats. After eight weeks, HFD and CD fed rats were randomly assigned to two types of surgery: IT and SHAM, then for 50% of animals of each group the diet was changed, whereas the other 50% received the same type of diet. Eight weeks after surgery the incretin level, glucose tolerance as well as body mass and insulin level were assessed. ResultsGLP-1 plasma concentration was significantly higher in the IT operated CD/CD group compared to fasting state and did not differ significantly from the SHAM operated CD/CD animals. IT influenced the glucose stimulated PYY plasma level when compared with SHAM operated animals in the CD/HFD group, where the PYY plasma level was higher than in the SHAM operated animals. The effect of IT as well as of pre and postoperative diet on GIP plasma levels were insignificant. The IT group members maintained on the CD were characterised by a lower fasting glucose level, both pre and postoperatively, compared with the SHAM operated animals. The effect of IT on the fasting glucose level in groups preoperatively maintained on an HFD was insignificant. ConclusionsIT surgery itself seems to have rather limited incretin effects in rats, whose obesity is the result of HFD.

Effects of high-fat diet on liver function and intestinal bacterial community in rats

Objective To investigate the influence of high-fat diet on liver function and intestinal bacterial community through building rat models. Methods 20 rats of 21 days old were divided into two groups randomly as normal diet group fed with standard chow diet and high-fat group fed with high-fat diet. After 6 weeks, feces of rats in both groups were obtained for 16S rRNA high-through sequencing of the intestinal bacterial community. Results After 6 weeks high-fat diet, total protein (TP)(55.79±3.75, P=0.002), globin (GLB)( 34.9±2.53, P<0.001), albumin (ALB)/GLB (.60±0.02, P<0.001), alkaline phosphatase (ALP)(373.80±63.05, P<0.001), total cholesterol (TC)(1.94±0.23, P<0.001), low density lipoprotein (LDL)(0.76±0.93, P<0.001), LDL/high density lipoprotein (HDL)(1.43±0.22, P<0.001), and triglyceride (TG)(1.48±0.50, P=0.015) increased compared with the normal diet group. Additionally, intestinal bacterial diversity and evenness decreased significantly. The dominant bacteria were Bacteroidetes, Firmicutes, and Proteobacteria, with averaged relative abundances as 56.36%, 35.31%, and 6.61%, respectively. The relative abundances of Bacteroidetes deceased (P=0.007), those of Firmicutes increased (P=0.020), and those of Proteobacteria were kept stable (P=0.928) after a 6-week high-fat diet. Furthermore, the intestinal bacterial community structure changed distinctly between the two groups by 16s rRNA high-through sequencing. Conclusion High-fat diet can lead to change of intestinal bacterial community structure and further result in liver function damnification as well as obesity. Key words: High-through sequencing; 16S rRNA; Rat; Intestinal bacterial community; Liver function

Influences of high-fat diet during pregnancy on sterol regulatory pathway and hepatic lipid deposition in male rat offspring

Objective To analyze the influences of maternal high-fat diet on male rat offspring's blood lipid level and hepatic lipid deposition as well as on the expression of two key factors, sterol regulatory element binding protein-1 (SREBP-1) and SREBP cleavage acting protein (SCAP), involved in hepatic cholesterol regulatory cascade during childhood and adulthood. Methods Pregnant Wistar rats were randomly divided into two groups: high fat diet (HF) group and normal intake control (NC) group (both n=20). Rats in the HF group were fed with high-fat diet till delivery before changing to a normal-fat diet, while the NC group was given the normal-fat diet all through the study. Male offspring born appropriate for gestational age (AGA) in different feeding groups were randomly selected as experimental subjects. Physical development, serum lipid levels and hepatic lipid deposition at the age of 7 and 24 weeks were compared between offspring of the two groups. Expression of SCAP and SREBP-1 at protein level was detected with immunohistochemistry. T test or Chi-square test was used for statistical analysis. Results The average birth weight of HF group was higher than that of NC group [(6.95±0.25) vs (6.79±0.78) g, t=2.088, P=0.038]. Large for gestational age (LGA) , AGA and small for gestational age (SGA) offspring accounted for 18.6% (21/113), 77.9% (88/113) and 3.5% (4/113) in HF group and 7.6% (10/132), 87.9% (116/132) and 4.5% (6/132) in NC group (χ2=13.500, P=0.001). At the age of 7 weeks, the offspring's body weight in HF group was higher than that in NC group [(68.78±7.55) vs (66.61±3.92) g, t=2.303, P=0.023]. At the age of 24 weeks, the body weight, body length and abdominal circumference of adult offspring in HF group were significantly higher than those in NC group [(251.74±24.04) vs (216.24±33.42) g, (22.60±0.79) vs (21.59±1.34) cm, (17.93±0.59) vs (16.83±0.88) cm;t=2.220, 2.379, 2.927, all P 0.05), but higher expression of SREBP-1 protein was observed in HF group than in NC group [(34.16±5.08)% vs (18.09±3.99)%, t=9.697, P<0.05]. At the age of 24 weeks, the expression levels of both SCAP and SREBP-1 proteins in liver tissues were higher in HF group than in NC group [(31.22±6.01)% vs (17.98±7.89)%, (61.33±16.25)% vs (29.76±11.21)%; t=2.303, 2.274, both P<0.05]. Conclusions High-fat intake during pregnancy can increase offspring's birth weight and the risk for LGA offspring. Maternal high-fat diet even up-regulates the expression of SCAP and SREBP-1 in male offspring born AGA in childhood and this impact become more obvious when reaching adulthood, resulting in excessive increase of body weight, body length and abdominal circumference and elevated serum lipid level and liver lipid deposition. Key words: Diet, high-fat; Lipidoses; Cholesterol; Weight gain; Birth weight; Pregnancy

EFEITOS DA DIETA HIPERLIPÍDICA SOBRE O SISTEMA HEPÁTICO NA ESQUISTOSSOMOSE MANSÔNICA EXPERIMENTAL

Schistosomiasis remains a serious public health issue and still belongs to the list of neglected diseases in Brazil with a significant socio-economic impact. It is estimated that 207 million people are infected, 500 thousand die annually and 120 million are asymptomatic. The characteristic pathological process is the presence of hepatic granuloma characterized as the body's defense reaction to egg insulation and protection against the release of their antigens. The aim of the study was to evaluate the influence of high fat diet on liver tissue in an experimental model of schistosomiasis mansoni using 35 female mice divided into 4 groups: fat diet and Infected - H + I (n = 9), Infected - I ( n = 7), high fat diet - H (n = 9) and control - C (n = 10). Tissue specimens were fixed and made histological and morphometric studies as numbers, volumes and granulomas developments, as well as quantification of collagen density. The prevailing characterization of granulomatous phase (FG) was observed in group I than H + I, along with a better collagen formation in the H + I group compared to the other groups. During the study we observed the absence of steatosis in H + I group. The study showed that the presence of fat diet alters some rearrangements in granulomatous formation, leading to the need for more intense observations about the theme.

The effect of high fat diet on daily rhythm of the core clock genes and muscle functional genes in the skeletal muscle of Chinese soft-shelled turtle (Trionyx sinensis).

In the present study, we sought to investigate the influence of high fat diet on the core clock genes and the muscle functional genes daily expression in the skeletal muscle of Chinese soft-shelled turtle. The turtles were fed by two diets including a control fat diet (the CON treatment, 7.98% lipid) and a high fat diet (the HFD treatment, 13.86% lipid) for six weeks and administrated by the photophase regimen of 24h light/dark (12L:12D) cycle. After the feeding trial experiment, we measured the daily expression levels of 17 core clock genes (Clock, Bmal1/2, NPAS2, Tim, Cry1/2, Per1/2, DBP, AANAT, NIFL3, BHLHE40, NR1D2, RORA, RORB, RORC) and 12 muscle functional genes (FBXO32, MBNL1, MSTN, Myf5, Myf6, MyoD, MyoG, MyoM1, PPARa, PDK4, Trim63, UCP3) in the skeletal muscle of the two treatments. The results showed that except for Bmal1, NPAS2, Per2 and RORB, the expression of the other 13 core clock genes exhibited circadian oscillation in the CON treatment. Among the 12 muscle functional genes, MBNL1, PDK4 and MyoM1 did not exhibit circadian oscillation in the CON treatment. In the HFD treatment, the circadian rhythms expressional patterns of the 8 core clock genes (Clock, Bmal2, Cry2, Per1, DBP, NFIL3, BHLHE40 and RORA) and 6 muscle functional genes (MSTN, Myf5, MyoD, MyoG, PPARa and Trim63) were disrupted. In addition, compared with the CON treatment, the circadian expression of the 5 core clock genes (Tim, Cry1, AANAT, NR1D2, RORC) and the 3 muscle functional genes (FBXO32, Myf6, UCP3) showed the advanced or delayed expression peaks in the HFD treatment. In CON treatment, the circadian expression of the MyoG, MyoD, Myf6, FBXO32 and PPARa showed positive or negative correlation with the transcription pattern of Clock, Bmal2, Cry1/2, Per1/2. However, only the FBXO32 and Myf6 presented positive or negative correlation with the circadian expression of Cry1, RORB, AANAT and Tim in HFD treatment. In summary, these results demonstrate that the disruption of the circadian rhythm of the core clock genes and muscle functional genes in the skeletal muscle is closely associated with feeding high fat diet to Chinese soft-shelled turtle.

The influence of high fat diets with different ketogenic ratios on the hippocampal accumulation of creatine – FTIR microspectroscopy study

The main purpose of this study was the determination and comparison of anomalies in creatine (Cr) accumulation occurring within CA3 and DG areas of hippocampal formation as a result of two high-fat, carbohydrate-restricted ketogenic diets (KD) with different ketogenic ratio (KR). To reach this goal, Fourier transformed infrared microspectroscopy with synchrotron radiation source (SRFTIR microspectroscopy) was applied for chemical mapping of creatine absorption bands, occurring around 1304, 1398 and 2800 cm−1. The samples were taken from three groups of experimental animals: control group (N) fed with standard laboratory diet, KD1 and KD2 groups fed with high-fat diets with KR 5:1 and 9:1 respectively. Additionally, the possible influence on the phosphocreatine (PhCr, the high energetic form of creatine) content was evaluated by comparative analysis of chemical maps obtained for creatine and for compounds containing phosphate groups which manifest in the spectra at the wavenumbers of around 1240 and 1080 cm−1. Our results showed that KD2 strongly modifies the frequency of Cr inclusions in both analyzed hippocampal areas. Statistical analysis, performed with Mann-Whitney U test revealed increased accumulation of Cr within CA3 and DG areas of KD2 fed rats compared to both normal rats and KD1 experimental group. Moreover, KD2 diet may modify the frequency of PhCr deposits as well as the PhCr to Cr ratio.

Influence of High-Fat Diet on Bone Tissue: An Experimental Study in Growing Rats.

The relationship between obesity and bone tissue remains contradictory, especially when the effect of high-fat diet is assessed in experimental models. The aim of this study was to evaluate the effects of high-fat diet on bone metabolism of growing rats. Twenty weaned female Wistar rats were equally divided into two groups: SD (standard diet) and HFD (high-fat diet with 60 % of energy as fat). After five weeks of the two diets, the rats were euthanized, and the liver, blood and bones extracted. The liver was analysed for malondialdehyde (MDA) and reduced glutathione (GSH) concentrations. Blood was analysed by the ELISA method for osteoprotegerin (OPG) and tumour necrosis factor ligand superfamily member 11 (TNFSF11/RANKL). The bone tissue was analysed by dual-energy X-ray absorptiometry (DXA), mechanical tests, computed microtomography, histological quantitative analysis and scanning electron microscopy. The gene expressions of PPAR-γ Runx-2, RANKL and Cathepsin-K were also evaluated. HFD caused an increase in the MDA concentration, indicating oxidative stress. It also increased the expression of PPAR-γ, which is the gene that is related to adipocyte differentiation. There was an increase in BMD of the tibia of animals fed with the HFD, but other microstructural and mechanical properties were maintained unaltered. In addition, there were no changes in the gene expressions related to the differentiation of osteoblasts and osteoclasts, as well as no changes to the biochemical markers of bone formation and bone resorption. Liver and gene parameters are changed in response to the HFD. However, although there was an increase in BMD, the microstructure and function of the bone did not change after a 5-week HFD.