High-calorie Diet Research Articles

Effect of Intermittent Fasting on Muscle Glycogen Stores in Rats with High-Calorie Diet

Insulin resistance in skeletal muscle is important since it is normally responsible for most of the insulin-mediated glucose disposal and contains the largest glycogen storage regulated by insulin sensitivity. A high-calorie diet is known to be a risk factor for insulin resistance. Lifestyle modification by regulating caloric intake through intermittent fasting (IF) is recommended to prevent insulin resistance. This study aims to analyze the effect of eight weeks of intermittent fasting on skeletal muscle glycogen stores in rats with a four-week high-calorie diet. A total 24 healthy male Wistar rats were divided into four groups, Ad-libitum with a standard diet (AL-SD) Ad-libitum with a high-calorie diet (AL-HCD) IF with a standard diet (IF-SD) IF with a high-calorie diet (IF-HCD). Muscles were obtained and stained with PAS stain to evaluate glycogen expression based on color intensity. The results of the glycogen expression score were obtained as follows, AL-SD=2.113±0.589 AL-HCD=1.827±0.375 IF-SD=2.109±0.499 IF-HCD=1.979±0.334. Although there was no significant difference between groups (p> 0.05), IF can prevent excessive reduction of glycogen stores in subjects with a HCD compared to the AL-HCD group. In conclusion, this study suggests that IF might improve the reduction of glycogen stores in muscles due to a high-calorie diet.

Fatty Liver/Adipose Tissue Dual-Targeting Nanoparticles with Heme Oxygenase-1 Inducer for Amelioration of Obesity, Obesity-Induced Type 2 Diabetes, and Steatohepatitis.

Persistent uptake of high-calorie diets induces the storage of excessive lipid in visceral adipose tissue. Lipids secreted from obese adipose tissue are accumulated in peripheral tissues such as the liver, pancreas, and muscle, and impair insulin sensitivity causing type 2 diabetes mellitus (T2DM). Furthermore, the accumulation of inflammatory cytokines and lipids in the liver induces apoptosis and fibrogenesis, and ultimately causes nonalcoholic steatohepatitis (NASH). To modulate obese tissue environments, it is challenged to selectively deliver inducers of heme oxygenase-1 (HO-1) to adipose tissue with the aid of a prohibitin targeting drug delivery system. Prohibitin binding peptide (PBP), an oligopeptide targeting prohibitin rich in adipose tissue, is conjugated on the surface of Hemin- or CoPP-loaded poly(lactide-co-glycolide) nanoparticles (PBP-NPs). PBP-NPs efficiently differentiate lipid storing white adipocytes into energy-generating brown adipocytes in T2DM and NASH models. In addition, PBP-NPs are found to target prohibitin overexpressed fatty liver in the NASH model and inhibit hepatic uptake of circulating lipids. Furthermore, PBP-NPs switch phenotypes of inflammatory macrophages in damaged organs and lower inflammation. Taken together, dual-targeted induction of HO-1 in fatty adipose and liver tissues is proven to be a promising therapeutic strategy to ameliorate obesity, insulin resistance, and steatohepatitis by lowering lipids and cytokines.

Grape Polyphenols in the Treatment of Human Skeletal Muscle Damage Due to Inflammation and Oxidative Stress during Obesity and Aging: Early Outcomes and Promises.

Today, inactivity and high-calorie diets contribute to the development of obesity and premature aging. In addition, the population of elderly people is growing due to improvements in healthcare management. Obesity and aging are together key risk factors for non-communicable diseases associated with several co-morbidities and increased mortality, with a major impact on skeletal muscle defect and/or poor muscle mass quality. Skeletal muscles contribute to multiple body functions and play a vital role throughout the day, in all our activities. In our society, limiting skeletal muscle deterioration, frailty and dependence is not only a major public health challenge but also a major socio-economic issue. Specific diet supplementation with natural chemical compounds such as grape polyphenols had shown to play a relevant and direct role in regulating metabolic and molecular pathways involved in the prevention and treatment of obesity and aging and their related muscle comorbidities in cell culture and animal studies. However, clinical studies aiming to restore skeletal muscle mass and function with nutritional grape polyphenols supplementation are still very scarce. There is an urgent need for clinical studies to validate the very encouraging results observed in animal models.

The Effect of Calorie Restriction on The Growth of Adipose Tissue in Mice

The aging process can be slowed by reducing the calorie intake consumed by the body by calorie restriction or fasting. This study aimed to analyze the effect of calorie restriction on adipose tissue in mice. The experimental research design uses 12 months old Rattus Novergicus Strain Wistar, weighing 250–300 grams. The intervention was carried out for 14 days, then the average weight of subcutaneous and visceral fat was measured using Kruskal Wallis analysis and ANOVA. Based on the four treatment groups, the mice fasting and given a high-calorie diet (group 4) had the highest average fat weight value of 4.02 grams in the subcutaneous and 3.55 grams in the visceral area. Meanwhile, in group 1, mice that were not fasting and did not get a high-calorie diet had the lowest average fat weight values, namely 2.14 grams in the subcutaneous area and 2.72 grams in the visceral area. Based on the test results, it was found that there was no difference between subcutaneous (p=0.121) and visceral (p=0.443) fat tissue in all groups. Calorie restriction is beneficial for delaying aging and increasing mammal life span, but intermittent calorie restriction does not affect adipose tissue.

Realgar Alleviated Neuroinflammation Induced by High Protein and High Calorie Diet in Rats via the Microbiota-Gut-Brain Axis.

Purpose: Gastrointestinal heat retention syndrome (GHRS) often occurs in adolescents, resulting into nervous system injury. Realgar, an arsenic mineral with neuroprotective effect, has been widely used to treat GHRS. However, its mechanism of action remains unknown. Methods: A GHRS rat model was established using a high protein and high calorie diet. We performed macroscopic characterization by assessing bowel sounds, hot/cold preference, anal temperature, and fecal features. Atomic fluorescence spectroscopy was employed to evaluate brain arsenic level while hippocampal ultrastructural changes were analyzed using transmission electron microscopy. In addition, inflammatory cytokines and BBB breakdown were analyzed by western blotting, immunofluorescence assays, and immunohistochemistry staining. We also evaluated hippocampal metabolites by LC-MS while fecal microorganisms were assessed by 16S rDNA sequencing. Results: Our data showed that the high protein and high calorie diet induced GHRS. The rat model depicted decreased bowel sounds, increased fecal characteristics score, preference for low temperature zone, and increased anal temperature. In addition, there was increase in inflammatory factors IL-6, Iba-1, and NF-κB p65 as well as reduced BBB structural protein Claudin-5 and Occludin. The data also showed appearance of hippocampus metabolites disorder and fecal microbial imbalance. Realgar treatment conferred a neuroprotective effect by inhibiting GHRS-specific characteristics, neuroinflammatory response, BBB impairment, metabolites disorder, and microbial imbalance in the GHRS rat model. Conclusion: Taken together, our analysis demonstrated that realgar confers a neuroprotective effect in GHRS rats through modulation of the microbiota-gut-brain axis.

Habitual behaviour associated with exposure to high-calorie diet is prevented by an orexin-receptor-1 antagonist

Habitual actions, which are associated with addictive behaviours, contribute to the loss of control of food seeking seen following exposure to calorie-dense foods in rats. Antagonism of orexin-receptor-1 (ORX-R1) has been shown to reduce a range of stimulus-driven feeding behaviours, but have yet to be implicated in the regulation of habitual actions. In the current study, male Long-Evans rats were given ‘binge-like’ access to high-calorie diet (HCD) or standard chow diet, and were subsequently trained to press a lever for food outcome. When lever responses were tested following outcome devaluation, chow-fed rats displayed goal-directed actions, whereas HCD-exposed rats displayed habitual actions. In study 1, it was shown that systemic administration of the ORX-R1 antagonist, SB-334867, prior to test restored goal-directed behaviour in HCD-exposed rats. In study 2, intra-nigral administration of SB-334867 similarly restored goal-directed behaviour, thereby implicating the substantia nigra as an important site for this effect. This study demonstrates that targeting ORX-R1 reduces habitual food seeking in male rats which may be important for understanding and treating compulsive feeding, obesity and binge eating disorder. This study also implicates the lateral hypothalamus, where ORX is produced, in mediating the expression of habits for the first time, and thus extends on the neurocircuits known to regulate habitual actions. Further investigation is required to determine whether the same effects are also seen in female rats, given that there are recognised sexual dimorphisms in feeding behaviour and a higher incidence of disordered eating in female than male populations.

Feeding behaviour, weight gain and blood sugar of male wistar rats fed on a high-calorie diet and vegetables

The transition in eating behaviour toward a diet rich in calories and low in vegetables is a major factor responsible for the rapid increase in the incidence of obesity and diabetes. The research aimed at investigating the effect of a high-calorie diet and vegetables on feeding behaviour, weight gain and blood sugar in male Wistar rats. The vegetables were dried, blended, and preserved in airtight containers. Thirty male Wistar rats weighing an average of 127.4 g were housed in 6 cages with 5 rats in each cage. There were six groups comprising the positive control which was fed standard rat feed and water, also the negative control which was given a high-calorie diet (high-fat feed and sugar water) and four treatment groups. The four treatment groups were fed on a high-calorie diet with a 5 % concentration of either Corchorus olitorius, Crassocephalum crepidiodes, Amaranthus hybridus or Solanecio biafrae respectively. Water (or sugar water) and feed intake of each group were measured and recorded daily. Weekly consumption of water and feed was computed for the entire 5 weeks of the experiment. The fasting blood sugar and weight of the test rats were recorded at baseline and weekly. Oral glucose tolerance test and serum insulin were determined at the end of the experiment using blood samples from the test rats. All results were analysed using ANOVA at p≤0.05 and means were separated with the use of Duncan’s multiple range tests (SPSS 20.0). The high-fat feed was significantly different from the standard rat feed in the composition of fat (26.79 g) and calories (422.67 kcal). The negative control and the treatment groups got adapted to feeding on the high-calorie diet before the end of the experimental period. Water and feed intakes of the positive control were only significantly higher during the first three and four weeks, respectively. At the end of the experiment, the positive control had the highest weight gain of 22 g which was significantly different at p≤0.05. C. crepidioides and S. biafrae significantly lowered the blood sugar (62.75 and 62.50 mg/dL) of the test rats. A. hybridus prevented insulin resistance by the attainment of peak level at 30 min alongside the positive control. There was a significant increase in the insulin level of the negative control while the vegetables prevented increased production of insulin. Key words: Blood sugar, Diabetes, Feeding behaviour, High-calorie, Insulin, Obesity, Vegetable, Weight gain

Effects of diet-induced obesity and its correction on sex hormone levels and behavioral featurеs of male Wistar rats

Obesity causes a wide range of pathophysiological consequences in the body, affecting the sphere of hormonal and psycho-emotional regulation. The aim of the study is to investigate the effect of a high-calorie diet on the development of obesity, reproductive status hormone levels and behavioral features of male Wistar rats, as well as the possibility of normalizing the identified shifts with non-medicinal options for obesity correction. Experiments were performed on 80 sexually mature male Wistar rats for 16 weeks and included 6 groups of animals, taking into account the diet (standard vivarium diet, highcalorie diet and transition from a high-calorie diet to a standard diet at the 2nd stage of the experiment) with or without the moderate physical activity in the form of treadmill running at the 2nd stage – the last 8 weeks of the experiment. A longterm high-caloric diet (16 weeks) caused visceral obesity, elevated glucose, cholesterol and triglyceride levels, dramatically decreased serum testosterone and estradiol levels, and depression manifestations in the Porsolt test in male Wistar rats. Successful correction of obesity, metabolic shifts and depressive behavior in rats was achieved by switching to a balanced diet during the last 8 weeks of the experiment. Normalization of testosterone and estradiol levels against the background of an increased serum luteinizing hormone level occurred in rats receiving a high-calorie diet (16 weeks) with the connection of physical exercise during the last 8 weeks of the experiment. Complex correction of obesity, which included the transition to a standard diet and exercise during the last 8 weeks of the experiment, led to a dramatic 2-fold increase in testosterone levels compared to control and a hyperactive phenotype in male Wistar rats. There is a close relationship between the depression development and testosterone levels in obesity and its correction.

Morphofunctional state of the liver of male Wistar rats during diet-induced obesity and its correction

Nonalcoholic fatty liver disease is the most common pathological condition inherent in obesity, which is associated with excessive accumulation of lipid droplets in hepatocytes, which, in turn, leads to the impaired functioning of the organ.The aim of the study is to investigate the effect of diet-induced obesity, as well as variants of its correction on morphofunctional characteristics of the liver tissue and biochemical indices of blood serum of male rats.The experiments were carried out on sexually mature male Wistar rats. The experiment consisted of two stages of 8 weeks each: 1) modeling obesity using a high-caloric diet (HCD); 2) obesity correction with the evaluation of the contribution of several experimental approaches: abandonment of HCD with a transition to a standard balanced diet and moderate physical activity in the form of running on a treadmill against the background of different caloric intakes.Keeping the rats for 16 weeks on HCD led to the formation of visceral obesity, fatty liver dystrophy, dyslipidemia, and disbalance of enzymatic processes – hyperbilirubinemia on the background of the reduced activity of aspartate aminotransferase and alanine aminotransferase in blood serum. The histoarchitectonics of the liver was partially restored with the preservation of inflammatory infiltration of the organ upon return to the standard diet. A return to the standard diet promoted a partial restoration of the liver histoarchitectonics with the preservation of inflammatory infiltration of the organ. When switching to a standard diet in combination with the moderate physical activity, a more pronounced restoration of the liver histostructure and signs of the active regeneration of the organ were observed.The most complete variant of correction of fatty hepatosis is the transition to a balanced diet in combination with the moderate physical activity.

An Underrated Diagnosis of Superior Mesenteric Artery Syndrome: A Case Report.

Superior mesenteric artery syndrome (Wilkie’s syndrome) is a rare cause of intestinal obstruction caused by a congenital or acquired reduction of the aorto-mesenteric angle leading to duodenal compression. We present the case of a 51-year-old female patient with a previous history of breast cancer. She was admitted to the Emergency Department with acute onset of recurrent vomiting, intense abdominal pain especially in the epigastric region, and abdominal distension. The ultrasound showed an absence of lower abdominal quadrants with an enlarged and distended stomach reaching the pelvis. The computer tomography scans confirmed the diagnosis of superior mesenteric artery syndrome. Conservative management was implemented, and using a nasogastric tube, and upped endoscopy approximately 4000 mL of fluid were aspirated with clinical improvement shortly after. The patient resumed a high-calorie diet and five months later, the patient was completely asymptomatic.

Optimizing nutrition in chronic pancreatitis

This review aims to discuss recent developments in the nutritional management in chronic pancreatitis. Nutritional assessment should be comprehensive and include dietary history, anthropometry, and biochemical nutritional parameters. Micronutrients should be evaluated at least yearly and dual-energy X-ray absorptiometry (DEXA) at every 2-yearly intervals. Studies on pancreatic enzyme replacement therapy (PERT) have primarily evaluated coefficient of fat excretion (CFA), coefficient of nitrogen excretion (CNA), and stool weight. Two RCTs, in which patients were treated with PERT for 7 days in a blinded manner and subsequently extended for 6-12 months in an open-label manner, showed improvement in nutritional parameters. However, two subsequent RCTs failed to show any benefit, and the most recent observational study demonstrated persistence of malnutrition even after PERT. The reason for the latter findings were nonadherence to PERT and poor oral intake of calories. Therefore, it is essential to educate the patients on adherence, counsel on taking high-protein, high-calorie diet, and supplement nutrients in those with inadequate oral intake. Other associated manifestations, such as diabetes and related complications, and anxiety/depression could also contribute to malnutrition directly or indirectly, and should, therefore, be adequately managed. Nutritional assessment should be performed meticulously. Nutritional therapy should not be restricted to only PERT and nutritional supplementation, but should also include dietary counselling and disease related education.

The parasitic worm product ES-62 protects the osteoimmunology axis in a mouse model of obesity-accelerated ageing.

Despite significant increases in human lifespan over the last century, adoption of high calorie diets (HCD) has driven global increases in type-2 diabetes, obesity and cardiovascular disease, disorders precluding corresponding improvements in healthspan. Reflecting that such conditions are associated with chronic systemic inflammation, evidence is emerging that infection with parasitic helminths might protect against obesity-accelerated ageing, by virtue of their evolution of survival-promoting anti-inflammatory molecules. Indeed, ES-62, an anti-inflammatory secreted product of the filarial nematode Acanthocheilonema viteae, improves the healthspan of both male and female C57BL/6J mice undergoing obesity-accelerated ageing and also extends median lifespan in male animals, by positively impacting on inflammatory, adipose metabolic and gut microbiome parameters of ageing. We therefore explored whether ES-62 affects the osteoimmunology axis that integrates environmental signals, such as diet and the gut microbiome to homeostatically regulate haematopoiesis and training of immune responses, which become dysregulated during (obesity-accelerated) ageing. Of note, we find sexual dimorphisms in the decline in bone health, and associated dysregulation of haematopoiesis and consequent peripheral immune responses, during obesity-accelerated ageing, highlighting the importance of developing sex-specific anti-ageing strategies. Related to this, ES-62 protects trabecular bone structure, maintaining bone marrow (BM) niches that counter the ageing-associated decline in haematopoietic stem cell (HSC) functionality highlighted by a bias towards myeloid lineages, in male but not female, HCD-fed mice. This is evidenced by the ability of ES-62 to suppress the adipocyte and megakaryocyte bias and correspondingly promote increases in B lymphocytes in the BM. Furthermore, the consequent prevention of ageing-associated myeloid/lymphoid skewing is associated with reduced accumulation of inflammatory CD11c+ macrophages and IL-1β in adipose tissue, disrupting the perpetuation of inflammation-driven dysregulation of haematopoiesis during obesity-accelerated ageing in male HCD-fed mice. Finally, we report the ability of small drug-like molecule analogues of ES-62 to mimic some of its key actions, particularly in strongly protecting trabecular bone structure, highlighting the translational potential of these studies.

Controlling the uncontrolled variation in the diet induced obese mouse by microbiomic characterization

Group sizes in an animal study are calculated from estimates on variation, effect, power and significance level. Much of the variation in glucose related parameters of the diet-induced obese (DIO) mouse model is due to inter-individual variation in gut microbiota composition. In addition, standard tandem repeats (STRs) in the non-coding DNA shows that inbred mice are not always homogenic. C57BL/6NTac (B6NTac) mice from Taconic and C57BL/6NRj (B6NRj) mice from Janvier Labs were fed a high calorie diet and treated with liraglutide. The fecal microbiota was sequenced before high-calorie feeding (time 1) and after diet-induced obesity instantly before liraglutide treatment (time 2) and mice were divided into clusters on the basis of their microbiota. Although liraglutide in both sub-strains alleviated glucose intolerance and reduced body weight, in a one-way ANOVA a borderline reduction in glycosylated hemoglobin (HbA1c) could only be shown in B6NTac mice. However, if the microbiota clusters from time 1 or time 2 were incorporated in a two-way ANOVA, the HbA1c effect was significant in B6NTac mice in both analyses, while this did not change anything in B6NRj mice. In a one-way ANOVA the estimated group size needed for a significant HbA1c effect in B6NTac mice was 42, but in two-way ANOVAs based upon microbiota clusters of time 1 or time 2 it was reduced to 21 or 12, respectively. The lowering impact on glucose tolerance was also powered by incorporation of microbiota clusters of both times in both sub-strains. B6NRj had up to six, while B6NTac had maximum three alleles in some of their STRs. In B6NRj mice in 28.8% of the STRs the most prevalent allele had a gene frequency less than 90%, while this was only 6.6% in the B6NTac mice. However, incorporation of the STRs with the highest number of alleles or the most even distribution of frequencies in two-way ANOVAs only had little impact on the outcome of data evaluation. It is concluded that the inclusion of microbiota clusters in a two-way ANOVA in the evaluation of the glucose related effects of an intervention in the DIO mouse model might be an efficient tool for increasing power and reducing group sizes in mouse sub-strains, if these have a microbiota, which influences these parameters.

Repetitive transcranial direct current stimulation modulates the brain–gut–microbiome axis in obese rodents

BackgroundComplex interactions between the brain, gut and adipose tissue allow to recognize obesity as a neurometabolic disorder. The recent data have shown that gut microbiota can play a potential role in obesity development. Transcranial direct current stimulation (tDCS) is a safe and non-invasive technique to modulate the activity of cerebral cortex and other connected brain areas also in context of appetite control. The objective of this study was to evaluate the effects of repetitive anodal tDCS (AtDCS) of prefrontal cortex on feeding behavior, metabolic status and selected phyla of gut microbiota in rats with obesity induced by high-calorie diet (HCD).Methods32 female Wistar rats were equally divided into 4 subgroups depending on diet effect (lean versus obese) and type of stimulation (active versus sham tDCS versus no stimulation). Feed intake, body weight, blood lipoproteins and leptin levels as well as Firmicutes and Bacteroidetes in intestines and stool were examined.ResultsHCD changed feeding behavior and metabolic parameters typically for obesity-related ranges and resulted in an abundance of Firmicutes at the expanse of Bacteroidetes in the large intestine and stool. AtDCS decreased appetite, body weight, and cholesterol levels. In addition, AtDCS reduced ratio of the average number of Firmicutes to average number of Bacteroidetes in all examined tissues.ConclusionsRepetitive AtDCS is not only effective for appetite restriction but can also modulate gut microbiome composition which demonstrates the existence of the brain–gut–microbiome axis and points at this technique as a promising complementary treatment for obesity. However, the effects should be further replicated in human studies.

Discovering Biomarkers for Non-Alcoholic Steatohepatitis Patients with and without Hepatocellular Carcinoma Using Fecal Metaproteomics

High-calorie diets lead to hepatic steatosis and to the development of non-alcoholic fatty liver disease (NAFLD), which can evolve over many years into the inflammatory form of non-alcoholic steatohepatitis (NASH), posing a risk for the development of hepatocellular carcinoma (HCC). Due to diet and liver alteration, the axis between liver and gut is disturbed, resulting in gut microbiome alterations. Consequently, detecting these gut microbiome alterations represents a promising strategy for early NASH and HCC detection. We analyzed medical parameters and the fecal metaproteome of 19 healthy controls, 32 NASH patients, and 29 HCC patients, targeting the discovery of diagnostic biomarkers. Here, NASH and HCC resulted in increased inflammation status and shifts within the composition of the gut microbiome. An increased abundance of kielin/chordin, E3 ubiquitin ligase, and nucleophosmin 1 represented valuable fecal biomarkers, indicating disease-related changes in the liver. Although a single biomarker failed to separate NASH and HCC, machine learning-based classification algorithms provided an 86% accuracy in distinguishing between controls, NASH, and HCC. Fecal metaproteomics enables early detection of NASH and HCC by providing single biomarkers and machine learning-based metaprotein panels.

Reducing ether lipids improves Drosophila overnutrition-associated pathophysiology phenotypes via a switch from lipid storage to beta-oxidation

High-calorie diets increase the risk of developing obesity, cardiovascular disease, type-two diabetes (T2D), and other comorbidities. These “overnutrition” diets also promote the accumulation of a variety of harmful lipids in the heart and other peripheral organs, known as lipotoxicity. However, the mechanisms underlying lipotoxicity and its influence on pathophysiology remain unknown. Our study uses genetics to identify the role of ether lipids, a class of potential lipotoxins, in a Drosophila model of overnutrition. A high-sugar diet (HSD) increases ether lipids and produces T2D-like pathophysiology phenotypes, including obesity, insulin resistance, and cardiac failure. Therefore, we targeted ether lipid biosynthesis through the enzyme dihydroxyacetonephosphate acyltransferase (encoded by the gene DHAPAT). We found that reducing DHAPAT in the fat body improved TAG and glucose homeostasis, cardiac function, respiration, and insulin signaling in flies fed a HSD. The reduction of DHAPAT may cause a switch in molecular signaling from lipogenesis to fatty acid oxidation via activation of a PPARα-like receptor, as bezafibrate produced similar improvements in HS-fed flies. Taken together, our findings suggest that ether lipids may be lipotoxins that reduce fitness during overnutrition.

The dynamic effects of maternal high-calorie diet on glycolipid metabolism and gut microbiota from weaning to adulthood in offspring mice.

Dysbiosis of gut microbiota can contribute to the progression of diabetes and obesity. Previous studies have shown that maternal high-fat (HF) diet during the perinatal period can alter the microbiota and induce metabolic disorders at weaning. However, whether dysbiosis of gut microbiota and metabolism could be recovered by a normal diet after weaning and the dynamic changes of gut microbiota have not been fully studied. In this study, C57BL/6J female mice were fed with a normal chow (NC) or HF diet for 4 weeks preconception, during gestation, and until pup weaning. After weaning, male offspring were fed with an NC diet until 9 weeks of age. The microbiota of offspring at weaning and 9 weeks of age was collected for 16S rRNA gene amplicon sequencing. We found that dams fed with an HF diet showed glucose intolerance after lactation. Compared with the offspring from NC dams, the offspring from HF dams exhibited a higher body weight, hyperglycemia, glucose intolerance, hyperinsulinemia, hypercholesterolemia, and leptin resistance and lower adiponectin at weaning. Fecal analysis indicated altered microbiota composition between the offspring of the two groups. The decrease in favorable bacteria (such as norank f Bacteroidales S24-7 group) and increase in unfavorable bacteria (such as Lachnoclostridium and Desulfovibrio) were strongly associated with a disturbance of glucose and lipid metabolism. After 6 weeks of normal diet, no difference in body weight, glucose, and lipid profiles was observed between the offspring of the two groups. However, the microbiota composition of offspring in the HF group was still different from that in the NC group, and microbiota diversity was lower in offspring of the HF group. The abundance of Lactobacillus was lower in the offspring of the HF group. In conclusion, a maternal HF diet can induce metabolic homeostasis and gut microbiota disturbance in offspring at weaning. Gut microbiota dysbiosis can persist into adulthood in the offspring, which might have a role in the promotion of susceptibility to obesity and diabetes in the later life of the offspring.

Effect of Calorie Restriction on Intestinal Inflammation in Mice Treated with a High-Calorie Diet

Abstract Inflammatory bowel disease (IBD) is classified into ulcerative colitis and Crohn's disease. It is chronic inflammation of gastrointestinal tract and idiopathic disease. Sugar is proved to be risk factor for IBD. Calorie restriction is a nutrition intervention to reduce energy intake and can reduce chronic desease. This study aims to determine the difference in the effect of a high-calorie diet and calorie restriction on intestinal inflammation. Eight-week-old healthy female Balb/c mice were divided into two groups. The high calorie (HC) group was fed standard diet plus oral gavage of glucose solution every day for 4 weeks. The dose of glucose solution was 0.0325 ml/gBW or 3-5% additional calories each day. The calorie restriction (CR) group had their calorie intake restricted to 50% of standard diet 3 times a week. After 4 weeks of treatment, the mice had their colon removed. The assessment of the intestinal inflammation was carried out using a light microscope, with a scoring system by Erben et al (2014) in HE staining. The mean score of the HC group was 1.22, this was higher than the CR group with a mean score of 1.18 even tough the result revealed that the scores of intestinal inflammation were not significantly different in the two groups (P = 0.827). However, there is no evidence for the underlying mechanism of intestinal inflammation by high-calorie diet and improvement of intestinal inflammation in high-calorie diet via calorie restriction. Thus, further research is needed on other calorie restriction methods in high-calorie diet study. Keywords: High calorie diet, Calorie restriction, Intestinal inflammation

Diet triggers specific responses of hypothalamic astrocytes in time and region dependent manner.

Hypothalamic astrocytes are particularly affected by energy-dense food consumption. How the anatomical location of these glial cells and their spatial molecular distribution in the arcuate nucleus of the hypothalamus (ARC) determine the cellular response to a high caloric diet remains unclear. In this study, we investigated their distinctive molecular responses following exposure to a high-fat high-sugar (HFHS) diet, specifically in the ARC. Using RNA sequencing and proteomics, we showed that astrocytes have a distinct transcriptomic and proteomic profile dependent on their anatomical location, with a major proteomic reprogramming in hypothalamic astrocytes. By ARC single-cell sequencing, we observed that a HFHS diet dictates time- and cell- specific transcriptomic responses, revealing that astrocytes have the most distinct regulatory pattern compared to other cell types. Lastly, we topographically and molecularly characterized astrocytes expressing glial fibrillary acidic protein and/or aldehyde dehydrogenase 1 family member L1 in the ARC, of which the abundance was significantly increased, as well as the alteration in their spatial and molecular profiles, with a HFHS diet. Together, our results provide a detailed multi-omics view on the spatial and temporal changes of astrocytes particularly in the ARC during different time points of adaptation to a high calorie diet.

The effect of modulators of hydrogen sulfide metabolism on morphological changes in kidneys of rats with high-calorie diet-induced obesity

Annotation. Obesity is one of the factors in the development of chronic kidney disease. Hydrogen sulfide (H2S) plays an important role in regulating the functional state of the kidneys, and its endogenous production is disrupted in obesity. The search for effective and safe correctors of H2S metabolism in the kidneys in obesity is relevant. The aim of the study was to establish the effect of potential modulators of H2S metabolism on biochemical and morphological changes in the kidneys of rats with high-calorie-diet-induced obesity (DIO). The experiments were performed on 60 white male laboratory rats in accordance with the principles of bioethics (Strasbourg, 1986; Kyiv, 2001). DIO was modeled using a high-calorie high-fat diet (39.5% fat per calorie). Metabolic correction was performed with H2S metabolism modulators (zinc sulfate, sodium thiosulfate, lipoic acid, taurine). Control rats received a standard diet (10.5% fat per calorie). Somatometric parameters, H2S level, morphological changes of kidney tissue were determined. Statistical processing was performed in the package IBM Statistics SPSS 26, differences were assessed in the Kruskel-Wallis test at a significance level of p<0.05. It was found that the development of DIO was accompanied by a decrease in the concentration of H2S in the kidneys (1.9 times, p<0.001), characteristic morphological changes in renal tissue with damage of the glomerular and tubular apparatus, severe inflammatory reaction of the parenchyma, endothelial damage and vascular structure. All metabolic correctors increased the level of H2S in the kidneys and inhibited the progression of nephropathy under the conditions of DIO. Zinc sulfate and lipoic acid were the most effective in preserving the structural elements of the renal parenchyma, while sodium thiosulfate and taurine were less effective.