High-calorie Diet Research Articles

Alzheimer’s Disease, Obesity, and Type 2 Diabetes: Focus on Common Neuroglial Dysfunctions (Critical Review and New Data on Human Brain and Models)

Background/Objectives. Obesity, type 2 diabetes (T2D), and Alzheimer’s disease (AD) are pathologies that affect millions of people worldwide. They have no effective therapy and are difficult to prevent and control when they develop. It has been known for many years that these diseases have many pathogenic aspects in common. We highlight in this review that neuroglial cells (astroglia, oligodendroglia, and microglia) play a vital role in the origin, clinical–pathological development, and course of brain neurodegeneration. Moreover, we include the new results of a T2D-AD mouse model (APP+PS1 mice on a high-calorie diet) that we are investigating. Methods. Critical bibliographic revision and biochemical neuropathological study of neuroglia in a T2D-AD model. Results. T2D and AD are not only “connected” by producing complex pathologies in the same individual (obesity, T2D, and AD), but they also have many common pathogenic mechanisms. These include insulin resistance, hyperinsulinemia, hyperglycemia, oxidative stress, mitochondrial dysfunction, and inflammation (both peripheral and central—or neuroinflammation). Cognitive impairment and AD are the maximum exponents of brain neurodegeneration in these pathological processes. both due to the dysfunctions induced by metabolic changes in peripheral tissues and inadequate neurotoxic responses to changes in the brain. In this review, we first analyze the common pathogenic mechanisms of obesity, T2D, and AD (and/or cerebral vascular dementia) that induce transcendental changes and responses in neuroglia. The relationships between T2D and AD discussed mainly focus on neuroglial responses. Next, we present neuroglial changes within their neuropathological context in diverse scenarios: (a) aging involution and neurodegenerative disorders, (b) human obesity and diabetes and obesity/diabetes models, (c) human AD and in AD models, and (d) human AD-T2D and AD-T2D models. An important part of the data presented comes from our own studies on humans and experimental models over the past few years. In the T2D-AD section, we included the results of a T2D-AD mouse model (APP+PS1 mice on a high-calorie diet) that we investigated, which showed that neuroglial dysfunctions (astrocytosis and microgliosis) manifest before the appearance of amyloid neuropathology, and that the amyloid pathology is greater than that presented by mice fed a normal, non-high-caloric diet A broad review is finally included on pharmacological, cellular, genic, and non-pharmacological (especially diet and lifestyle) neuroglial-related treatments, as well as clinical trials in a comparative way between T2D and AD. These neuroglial treatments need to be included in the multimodal/integral treatments of T2D and AD to achieve greater therapeutic efficacy in many millions of patients. Conclusions. Neuroglial alterations (especially in astroglia and microglia, cornerstones of neuroinflammation) are markedly defining brain neurodegeneration in T2D and A, although there are some not significant differences between each of the studied pathologies. Neuroglial therapies are a very important and p. promising tool that are being developed to prevent and/or treat brain dysfunction in T2D-AD. The need for further research in two very different directions is evident: (a) characterization of the phenotypic changes of astrocytes and microglial cells in each region of the brain and in each phase of development of each isolated and associated pathology (single-cell studies are mandatory) to better understand the pathologies and define new therapeutic targets; (b) studying new therapeutic avenues to normalize the function of neuroglial cells (preventing neurotoxic responses and/or reversing them) in these pathologies, as well as the phenotypic characteristics in each moment of the course and place of the neurodegenerative process.

Reducing binge eating behavior in rats using the novel ghrelin receptor antagonist Agrelax

BACKGROUND: Binge eating disorder is the most common eating disorder, characterized by recurrent episodes of binge eating during which a person consumes excessive amounts of food in the absence of hunger. These episodes of binge eating are usually accompanied by a feeling of lack of control with an inability to refrain from eating or stop eating once it has started. A rodent model of binge eating disorder shows that intermittent consumption of energy-dense foods induces binge eating behavior independent of weight gain. AIM: To study the effect of the ghrelin receptor antagonist Agrelax on compulsive overeating in rats. MATERIALS AND METHODS: The study involved 30 male Wistar rats. To model compulsive overeating, animals received high-calorie food (a mixture based on chocolate-nut butter spread) 3 times a week while maintaining free access to standard pelleted food and water. Compulsivity in behavior was assessed using the pellet burying test. The ghrelin receptor antagonist Agrelax was administered intranasally, 1 µg/1 µl, 10 µl in each nostril for 7 days. RESULTS: Compulsive behavior was assessed using the pellet burying test. The experimental group of animals receiving a high-calorie diet buried a significantly larger number of pellets than the control group (p 0.01). After a 7-day course of Agrelax, the number of buried balls decreased significantly, reaching the values of the control group (p 0.05). A technique for compulsive overeating in rats was developed by giving high-calorie food 3 times a week. After a 7-day course of Agrelax, the consumption of high-calorie foods significantly decreased (p 0.05). The daily consumption of standard feed in the group did not differ compared to the control group. However, after the course of Agrelax administration, the consumption of standard feed decreased. CONCLUSIONS: The data obtained suggest new ways of synthesizing peptide pharmacological agents based on ghrelin and its antagonists for the correction of food addiction.

Inhibition of ketohexokinase prevents fructose-induced insulin resistance and endothelial dysfunction in high fat and sucrose-fed mice via enhancing energy expenditure

Abstract Introduction Cardiovascular disease linked to fatty liver poses a significant threat to health. Consumption of high-fat diets (HFD) is known to trigger a cascade of health issues including obesity, diabetes and non-alcoholic fatty liver disease (NAFLD). These conditions are exacerbated, with the addition of dietary sugar to high-fat diets (HFSD), resulting in non-alcoholic steatohepatitis (NASH). Studies have shown that fructokinase (ketohexokinase or KHK) knockdown protects mice from HFSD-induced NASH. Purpose This study focused on examining the temporal changes of metabolic perturbations, triggered by sugar consumption, particularly in the transition from fatty liver to cardiovascular disease. Methods C57/BL6 wild type (WT) and KHK-knockout mice were fed with HFD or HFSD for different durations between 6 to 20 weeks, to induce NAFLD and NASH. Western blotting and quantitative-PCR were carried out on tissues and isolated endothelial cells for protein and mRNA expressions, respectively. Glucose and insulin tolerance tests and whole-body energy measurements were performed at different time-points. Combined Laboratory Animal Monitoring System was used to monitor various parameters of energy expenditure. Functional interactions between endothelial cells and adipose tissues were carried out using an in-house Organ-On-a-chip technology. Endothelial function was studied by measuring isometric tensions in organ bath. Results KHK-deficient mice had significantly lower weight compared to WT littermates. Wild-type mice fed HFD and HFSD exhibited significant glucose intolerance, insulin resistance, and endothelial dysfunction compared to KHK-knockout mice. However, HFSD led to more severe outcomes compared to HFD, demonstrating differing temporal effects on glucose intolerance and insulin resistance. Interestingly, KHK-knockout mice were significantly protected from the effects induced by HFSD, as well as, such as increased body weight, fasting hyperglycemia, hyperinsulinemia and endothelial function. KHK-knockout mice exhibited significant increase in oxygen consumption and energy expenditure, both in HFD and HFSD-fed conditions. These data suggest that high energy-expenditure is one of the primary mechanisms, in reducing adiposity and body weight in HFSD-fed knockout mice. Notably, KHK-deficient mice were protected against sugar-induced fat accumulation, random hyperinsulinemia and significant impairment of endothelial function. Conclusions A novel finding in this study is that KHK ablation protects not only against HFSD-induced, but also HFD-induced pathologies via significantly enhancing energy expenditure. The results suggest that targeting KHK could potentially mitigate the development of fatty liver and cardiovascular diseases, induced by high calorie diets.

Dissecting implicit food-related behaviors in Binge Eating Disorder and obesity: insights from a mobile approach-avoidance framework.

Bulimic episodes experienced by patients with Binge Eating Disorder (BED) might be sustained by an enhanced behavioral propensity to approach food stimuli. To test this hypothesis, automatic approach avoidance tendencies toward high-calorie foods (HCF), low-calorie foods (LCF), and neutral objects were assessed in a group of 23 patients with BED, and their performance was compared to the one of 17 patients with obesity without BED and a group of 32 normal weight participants. All participants performed a mobile approach-avoidance task in which they were required to approach and avoid different stimuli by respectively pulling their phone toward themselves or pushing it away. Reaction times were analyzed. Results showed a significant three-way interaction between group, type of movement and stimulus. Post-hoc analyses revealed that all the groups displayed an approach bias toward HCF. Patients with BED and healthy controls also displayed an approach bias toward LCF, a bias that was absent in obese individuals without BED. Moreover, patients with BED were faster in approaching food stimuli, both HCF and LCF, compared to healthy controls. These behavioral tendencies are quite consistent with the real-life attitudes of both BED patients and patients with obesity and might contribute to the maintenance of unhealthy eating habits such as binging in patients with BED and high-calorie diets in patients with obesity.

A Systematic Review of Metabolic Syndrome: Key Correlated Pathologies and Non-Invasive Diagnostic Approaches.

Background and Objectives: Metabolic syndrome (MetS) is a condition marked by a complex array of physiological, biochemical, and metabolic abnormalities, including central obesity, insulin resistance, high blood pressure, and dyslipidemia (characterized by elevated triglycerides and reduced levels of high-density lipoproteins). The pathogenesis develops from the accumulation of lipid droplets in the hepatocyte (steatosis). This accumulation, in genetically predisposed subjects and with other external stimuli (intestinal dysbiosis, high caloric diet, physical inactivity, stress), activates the production of pro-inflammatory molecules, alter autophagy, and turn on the activity of hepatic stellate cells (HSCs), provoking the low grade chronic inflammation and the fibrosis. This syndrome is associated with a significantly increased risk of developing type 2 diabetes mellitus (T2D), cardiovascular diseases (CVD), vascular, renal, pneumologic, rheumatological, sexual, cutaneous syndromes and overall mortality, with the risk rising five- to seven-fold for T2DM, three-fold for CVD, and one and a half-fold for all-cause mortality. The purpose of this narrative review is to examine metabolic syndrome as a "systemic disease" and its interaction with major internal medicine conditions such as CVD, diabetes, renal failure, and respiratory failure. It is essential for internal medicine practitioners to approach this widespread condition in a "holistic" rather than a fragmented manner, particularly in Western countries. Additionally, it is important to be aware of the non-invasive tools available for assessing this condition. Materials and Methods: We conducted an exhaustive search on PubMed up to July 2024, focusing on terms related to metabolic syndrome and other pathologies (heart, Lung (COPD, asthma, pulmonary hypertension, OSAS) and kidney failure, vascular, rheumatological (osteoarthritis, rheumatoid arthritis), endocrinological, sexual pathologies and neoplastic risks. The review was managed in accordance with the PRISMA statement. Finally, we selected 300 studies (233 papers for the first search strategy and 67 for the second one). Our review included studies that provided insights into metabolic syndrome and non-invasive techniques for evaluating liver fibrosis and steatosis. Studies that were not conducted on humans, were published in languages other than English, or did not assess changes related to heart failure were excluded. Results: The findings revealed a clear correlation between metabolic syndrome and all the pathologies above described, indicating that non-invasive assessments of hepatic fibrosis and steatosis could potentially serve as markers for the severity and progression of the diseases. Conclusions: Metabolic syndrome is a multisystem disorder that impacts organs beyond the liver and disrupts the functioning of various organs. Notably, it is linked to a higher incidence of cardiovascular diseases, independent of traditional cardiovascular risk factors. Non-invasive assessments of hepatic fibrosis and fibrosis allow clinicians to evaluate cardiovascular risk. Additionally, the ability to assess liver steatosis may open new diagnostic, therapeutic, and prognostic avenues for managing metabolic syndrome and its complications, particularly cardiovascular disease, which is the leading cause of death in these patients.

Effectiveness of Prebiotics and Mediterranean and Plant-Based Diet on Gut Microbiota and Glycemic Control in Patients with Prediabetes or Type 2 Diabetes: A Systematic Review and Meta-Analysis

Background: A high-calorie diet results in the development of prediabetes (PD) or type 2 diabetes mellitus (T2DM). This diet has been reported to cause changes in microbial composition, concentration levels of glycemic parameters, and immune cells or inflammatory cytokines. This systematic review and meta-analysis aimed to evaluate the effects of prebiotics, as well as Mediterranean and plant-based dietary interventions, on gut microbiota composition and glucose homeostasis in individuals with PD or T2D. Methods: This systematic review and meta-analysis was developed according to the 2020 PRISMA guidelines and checklist. PubMed, EBSCOhost and Google Scholar were the three databases that were used to search for electronically published studies. Data extraction was conducted and examined by the reviewers and all the eligible studies were selected. To test for the quality and biases of the included studies, the Downs and Black checklist was used, followed by the use of Review Manager 5.4. A forest plot was used for meta-analysis and sensitivity analysis. The strength of the evidence was assessed using the Grading of Recommendation Assessment, Development and Evaluation approach. Results: Overall, eight studies met the inclusion criteria: seven focused on patients with T2D, and one focused on patients with PD. The prebiotic dietary intervention did not have a statistically significant effect on glycemic control, including fasting blood glucose (FBG) and glycated hemoglobin (HbA1c). However, one study investigating the Mediterranean diet reported a significant effect on glycemic control. Both prebiotic and Mediterranean dietary interventions were found to beneficially influence gut microbial composition in the intervention groups compared to the placebo groups. No studies assessed the impact of a plant-based diet on microbial composition and glucose parameters. Conclusions: This review indicated that dietary intervention with a prebiotic or Mediterranean diet shows to beneficially improve the gut microbiota composition of Firmicutes, Bacteroidetes and Bifidobacteria in patients with PD or T2D. However, their beneficial effects on FBG and HbA1c were less clear and uncertain due to limited reports, particularly regarding the Mediterranean dietary intervention.

CHANGES IN SECONDARY STRUCTURE OF PROTEIN IN SKELETAL MUSCLE DUE TO HIGH-CARBOHYDRATE OR HIGH-FAT DIETS

Objective: Obesity, which arises from changes in lifestyle and feeding habits, is a threat to human health. One essential contributor to the increase in obesity rates is the popularity of high-calorie diets. This study aims to investigate high-fat (HFD) and high-carbohydrate (HCD) diet-induced molecular changes in protein secondary structure in longissimus dorsi skeletal muscle tissues of female inbred C57BL/6J mice by utilizing Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) spectroscopy. Materials and Methods: Mice were fed a control diet, HCD, or HFD for 24 weeks. Their skeletal muscle tissues were collected, and their spectra were recorded using a Bruker Invenio S ATR-FTIR spectrometer in the 4000-400 cm-1 region. Results: The protein secondary structure profiles of the HCD group demonstrated a significant rise in antiparallel β-sheet and β-turn and a decline in parallel β-sheets together with the insignificant increase in aggregated β-sheets and a decrease in α-helix. The impact of an HFD on protein conformation is less pronounced than HCD. The HFD diet led to an increase in antiparallel β-sheets and a decrease in parallel β-sheets. Although it was not significant, an increase was observed in β-turn and α-helix. Conclusion: These results propose the appearance of protein aggregation and/or formation of protein-protein intermolecular interaction in skeletal muscle tissues of female inbred C57BL/6J mice. Collectively, these data suggest that both high-calorie diets impair secondary structures of protein in skeletal muscle that may affect its metabolic function.

THE IMPACT OF HOP EXTRACT ACTIVE COMPONENTS ON METABOLIC DISTURBANCES IN ESTROGEN DEFICIENT FEMALE RATS WITH PREDIABETES

A number of studies have shown a greater cardiovascular risk in women with type 2 diabetes compared to men. The latter may be due to more excessive manifestations of metabolic disorders in women, in particular postmenopausal, that develop even at the stage of prediabetes. Since the use of hormone replacement therapy in women after menopause had adverse results on the progression of cardiovascular events, an alternative method of reducing cardiovascular risk in postmenopausal women with prediabetes may be the use of phytoestrogens, which possess estrogen-like activity without negative side effects specific to exogenous estrogens. The aim of our study was to evaluate the effect of hop extract on metabolic disturbances in female rats with prediabetes under estrogen deficiency. Materials and methods. The study was conducted on three-month-old intact and ovariectomized Wistar rats with metabolic syndrome (MS) induced by high calorie diet (15% lard, 25% sucrose, 1% bile salts, 59% standard feed) for eight weeks. The test substances were administered intragastrically once per day in a dose of 20 μg/kg or 200 μg/kg b.w. in recalculation on 8-prenylnaringenin for hop extract and 200 μg/kg b.w. in recalculation on estradiol for the reference drug, from the fifth week after induction of metabolic syndrome. Results. It was revealed that administration of hop extract in a dose of 200 μg/kg, similar to estradiol, led to improvement in glucose tolerance and decrease in insulin resistance (p˂0.05) in estrogen deficient rats with MS. In contrast to estradiol, hop extract had no effect on the mass of uterus in ovariectomized animals. The use of hop extract only in the dose of 200 μg/kg, similar to estradiol, was accompanied by a significant decrease in body weight gain and visceral fat, as well as normalization of the total lipids content in serum of experimental animals (p˂0.05). It is of note, that hop extract resulted in decrease of hypertriglyceridemia (p˂0.05), but did not affect the level of total cholesterol, while estradiol reduced the concentration of total cholesterol (p˂0.05), and had no effect on the level of triglycerides. Hop extract in a dose of 200 μg/kg, as well as estradiol, led to a decrease in the intensity of lipid peroxidation induced by MS under estrogen deficiency, as evidenced by reduced concentration of conjugated dienes in serum (p˂0.05). At the same time, the total antioxidant activity of serum in these animals remained elevated compared to intact group. In rats with MS and hypoestrogenia, hop extract in the highest dose and estradiol resulted in complete normalization (p˂0.05) of the decreased level of NO stable metabolites in serum and the reduced activity of NO-synthase in heart. Conclusions. The revealed cardioprotective effect of hop extract that is realized due to the improved lipid profile and reduced insulin resistance, visceral obesity, oxidative stress and endothelial dysfunction in estrogen deficient female rats with MS indicates the prospects of its use for prevention and treatment of cardiovascular complications in postmenopausal women with prediabetes.

Effect of diet-induced obesity and non-drug options of its correction on the functional and morphological liver characteristics in female Wistar rats

A nonalcoholic fatty liver disease is one of the unfavorable consequences of obesity. However, experimental studies on the mechanisms of this pathology development are being carried out mainly on male rodents, and the data on the development of fatty hepatosis in females are insufficient.The aim of the study was to investigate the effect of diet-induced obesity and non-drug options for its correction on the morphological liver characteristics and liver metabolic parameters in female Wistar rats. Experiments were conducted on sexually mature female Wistar rats and included the study of morphological and biochemical parameters of the liver functional state in animals kept on standard diet (StD, 16 weeks), on a high-calorie diet (HCD, 16 weeks) when switching to a standard diet (HCD/StD, 8/8 weeks), when the physical activity in the form of treadmill running was included (StD + running, HCD + running and HCD/StD + running, 8/8 weeks).Long-term use of HCD in female rats caused visceral obesity, liver fatty dystrophy with disruption of organ histoarchitectonics, shifts in hepatic metabolism and increased lipid peroxidation. Correction of diet-induced obesity by switching to StD led to a complete or partial normalization of the studied indices. In the “HCD + running” group, metabolic disorders are often more pronounced than in the “HCD” group. The transition to HCD/StD + running promoted the most complete restoration of metabolism and histostructure of the liver with regeneration signs of the organ.Thus, an optimal correction of visceral obesity, fatty liver dystrophy and its metabolism is impossible without diet normalization in female Wistar rats. An additional regenerating effect with respect to the liver histostructure is achieved with a combined variant of correction ‒ transition to a balanced diet and moderate physical activity.

Abstract MP04: Brain miR-410-3p Expression Sex-dependently Reduces Ang-II-induced Hypertension

Dysregulation of microRNA (miRNA) is associated with hypertension and other diseases. We previously observed direct interaction of miR-410-3p with AT 1 R and sex-dependent downregulation of miR-410-3p in the hypothalamus of a mouse cardiometabolic disease (CMD) model, suggesting a possible involvement in the development of CMD through modulation of the renin-angiotensin system. To further investigate the role of hypothalamic miR-410-3p expression as a therapeutic target for hypertension, acute Ang-II injection and chronic infusion experiments were performed. In acute experiments, C57BL/6J mice (males and females) were injected with Lenti-miR-410-3p or a control virus (icv, 2 µl, n=5-6). After 3 weeks, mice were anesthetized and a catheter was inserted to the carotid artery for blood pressure (BP) monitoring, followed by a bolus icv injection of Ang-II (200 ng/200 nl). Changes in systolic BP (ΔSBP) were recorded. In chronic experiments, mice were fed with a high calorie diet for 2 months before icv virus injection (2 µl). Telemetry probes (DSI) were implanted for conscious BP monitoring. Three weeks following virus injection, all mice were infused with Ang-II using osmotic minipumps (sc, 600 ng/kg/min, 14 days) to induce CMD. BP was recorded weekly and 24 h average of mean arterial pressure (MAP) was calculated. Acute Ang-II injection-induced pressor responses were similar in males (ΔSBP; 22.2±4.7 mmHg) and females (20.6±6.5 mmHg) transfected with the control virus. In lenti-miR-410-3p transfected mice, the pressor responses were blunted in both males (6.7±4.8 mmHg, P <0.001 vs. control) and females (10.9±4.7 mmHg, P<0.05 vs. control), with a greater reduction observed in males (69.8% vs. 47%). In the HCD model, baseline MAP was not different between male control and Lenti-miR-410, or female control and Lenti-miR-410 group. Following Ang-II infusion, MAP was increased in both sexes treated with control virus. Interestingly, this increase was blunted by Lenti-miR-410-3p expression in males (137.3 ± 9.4 vs. 160.7 ± 4.3 mmHg, P =0.05) but not in females (140.4±4.6 vs. 140.5 ± 4.2 mmHg). These data are aligned with our previous findings that male mice had higher expression of hypothalamic AT 1 R than in females in CMD. In summary, miR-410-3p inhibits both acute and chronic Ang-II induced increases in BP in a sex-dependent manner, with more profound effects in males. miR-410-3p could be a new strategy for the treatment of hypertension in CMD.

Efficacy of L-cysteine in increasing circulatory hydrogen sulfide, nitrite, and 25(OH)VD levels in ZDF rats and in vitro treatment of H2S and NO2 in upregulating VD hydroxylase genes in monocytes

Dairy products, such as whey proteins, have been effectively utilized to enhance the effectiveness of vitamin D fortification and optimize circulating 25(OH)VD levels. Whey protein is rich in L-cysteine (LC) which is the precursor of hydrogen sulfide (H2S), enhances glutathione (GSH) biosynthesis, and promotes positive nitrogen balance. Zucker diabetic rats (ZDF) were used as a model in this study, to examine the hypothesis that LC supplementation enhances blood levels of H2S and nitrite (NO2) while reducing inflammation biomarkers. Rats were gavaged daily (orally) with either saline placebo or L-cysteine along with a high-calorie diet starting at 6 weeks of age. Fasting blood levels showed LC supplementation significantly increased circulatory levels of H2S and NO2 compared with placebo rats. LC supplementation increased plasma concentration of 25(OH)VD and vitamin C and lowered leptin and body weight gain in ZDF rats. Furthermore, to assess the impact of H2S and NO2 in raising 25(OH)VD levels, the in vitro effect of H2S/NO2 on vitamin D metabolism genes was examined using THP-1 monocytes. The exogenous H2S and NO2 treatment upregulated the relative expression of CYP2R1 and CYP27B1 genes in cultured monocytes. This study suggests a potential mechanism for the observed increase in circulating 25(OH)VD levels following L-cysteine supplementation.

Narrative review of diagnosis, management and treatment of dysphagia and sialorrhea in amyotrophic lateral sclerosis.

The degenerative motor neuron disorder amyotrophic lateral sclerosis (ALS) frequently leads bulbar symptoms like dysarthria, dysphagia, and sialorrhea, in approximately one-third of cases being the initial symptom. Throughout the disease, more than two-thirds of ALS patients experience dysphagia, regardless of the region of onset. In this review, we aimed to offer an updated overview of dysphagia and sialorrhea in ALS, covering its diagnosis, monitoring, and treatment in clinical practice. Regular assessment of dysphagia and sialorrhea during each patient visit is essential and should be a standard aspect of ALS care. Early discussion of potential treatments such as high-calorie diets or percutaneous endoscopic gastrostomy (PEG) is crucial. Furthermore, this review highlights and discusses potential areas for improvement in both clinical practice and research.

Salvia elegans Vahl Counteracting Metabolic Syndrome and Depression in Mice on a High-Fat Diet.

Salvia elegans Vahl is a plant commonly used in Mexico as a remedy for nervous disorders, inflammatory diseases, and "ringing in the ears"; the latter can be associated with arteriosclerotic conditions and arterial hypertension. Therefore, based on medicinal use, this work aimed to evaluate the hydroalcoholic extract (SeHA, 100 mg/kg) of this plant and two fractions, ethyl acetate (SeFAc, 50 mg/kg), and obtained from SeFAc fractionation denominated SeF3 (10 mg/kg), on several alterations derived from metabolic syndrome (MetS) derived from the ingestion of a high-calorie diet (high-fat diet), in ICR (Institute of Cancer Research) mice, leading to chronic inflammation that results in neurological damage such as depression. Therefore, several MetS-related parameters, such as forced swim tests, hypertension, serum corticosterone levels, glucose, triglycerides, cholesterol, adiposity index, and insulin resistance, will be evaluated. Additionally, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-10 levels were measured in kidneys, fat tissue, brains, and spleens. It was proven that all those S. elegans-derived treatments reversed the damage, showing antidepressant, antihypertensive, antihyperglycemic, and antidyslipidemic effects and decreased adiposity, insulin resistance, and serum corticosterone. They induced a modulatory response by modifying the levels of TNF-α, IL-1β, IL-6, and IL-10 in different organs. High-performance liquid chromatography (HPLC) analysis of the acetate of ethyl fraction from S. elegans (SeFAc) fraction revealed the presence of rosmarinic and caffeic acids as well as flavonoids, while the fraction from SeFAc called SeF3 Was identified by gas mass as methyl glucose, glycerol, and known sterols, among others. Thus, it was concluded that S. elegans protects against the harmful effects of MetS.

Association between metabolic disorders and clinicopathologic features in endometrial cancer.

In recent years, the incidence of Endometrial cancer (EC) has been on the rise due to high-fat, high-calorie diets and low-exercise lifestyles. However, the relationships between metabolic disorders and the progression of EC remain uncertain. The purpose of our study was to explore the potential association between obesity, hypertension, hyperglycemia and clinicopathologic characteristics in EC patients. In categorical variables, Chi-square tests were used to calculate P values. Univariate logistic regression and multivariate logistic regression were used to identify the risk factors of myometrial invasion>1/2 and lymph node metastasis. Overall survival (OS) was estimated using the Kaplan-Meier method. The study included 406 individuals with EC, 62.6% had type I and 37.4% had type II. Hypertension was seen in 132 (32.5%), hyperglycemia in 75 (18.5%), and overweight or obesity in 217 (53.4%). Hypertension, hyperglycemia, and obesity are strongly associated with the clinicopathologic features of EC. Multivariate logistic regression revealed that hyperglycemia (OR=2.439,95% CI: 1.025-5.804, P = 0.044) was a risk factor for myometrial invasion depth >1/2 in patients with type I EC, and hypertension (OR=32.124,95% CI: 3.287-313.992, P = 0.003) was a risk factor for lymph node metastasis in patients with type I EC. Survival analysis found that hyperglycemia (P < 0.001) and hypertension (P = 0.002) were associated with OS in type I EC. Neither hyperglycemia, hypertension, nor obesity were associated with the prognosis in type II EC. Hyperglycemia was a risk factor for myometrial invasion depth >1/2 in patients with type I EC and hypertension was a risk factor for lymph node metastasis in patients with type I EC. Hypertension and hyperglycemia were associated with poor prognosis in patients with type I EC.

Striped Catfish Oil and Turmeric Extract-Reduce Inflammation and Insulin Resistance on Metabolic Syndrom: A Review

Metabolic Syndrome is continuing to grow worldwide. Indonesia is no exception. High-calorie diets and physical inactivity trigger several pathways involved in metabolic syndrome. These include inflammation and insulin resistance. Associated with type 2 diabetes mellitus, cardiovascular disease, and death, metabolic syndrome is important. There is therefore a need for early intervention to reduce the complications of this disease. Striped catfish (Pangasius hypophthalmus) is one of the freshwater fish farmed in Indonesia. Turmeric (Curcuma longa Linn.) is also widely used in Indonesian food preparations. This review aims to focus on striped catfish oil and turmeric extract that positively affect inflammation and insulin resistance in the intervention of metabolic syndrome. This review shows that striped catfish oil contains omega-3 fatty acids (EPA and DHA), while turmeric extract contains flavonoids, tannins, and saponins. Based on the results of the review, it is known that bioactive compounds found in catfish oil and turmeric extract can be used as nutraceutical ingredients to intervene in metabolic syndrome.

The rs2341471-G/G genotype of activating transcription factor 6 (ATF6) is the risk factor of type 2 diabetes in subjects with obesity or overweight.

Numerous studies have demonstrated that the onset of type 2 diabetes (T2D) is linked to the reduction in ß-cell mass caused by apoptosis, a process initiated by endoplasmic reticulum (ER) stress. The aim of this study was to investigate the associations between single nucleotide polymorphisms (SNPs) in the ATF6 gene (activating transcription factor 6), a key sensor of ER stress, and T2D susceptibility. The study involved 3229 unrelated individuals, including 1569 patients with T2D and 1660 healthy controls from Central Russia. Four functionally significant intronic SNPs, namely rs931778, rs90559, rs2341471, and rs7517862, were genotyped using the MassARRAY-4 system. The rs2341471-G/G genotype of ATF6 was found to be associated with an increased risk of T2D (OR = 1.61, 95% CI 1.37-1.90, PFDR < 0.0001). However, a BMI-stratified analysis showed that this genotype and haplotypes CGGA and TAGA are associated with T2D risk exclusively in subjects with obesity or overweight (PFDR < 0.05). Despite these patients being found to have higher consumption of high-carbohydrate and high-calorie diets compared to normal-weight individuals (P < 0.0001), the influence of the rs7517862 polymorphism on T2D risk was observed independently of these dietary habits. Functional SNP annotation revealed the following: (1) the rs2341471-G allele is associated with increased ATF6 expression; (2) the SNP is located in a region exhibiting enhancer activity epigenetically regulated in pancreatic islets; (3) the rs2341471-G was predicted to create binding sites for 18 activating transcription factors that are part of gene-regulatory networks controlling glucose metabolism and maintaining proteostasis. The present study revealed, for the first time, a strong association between the rs2341471-G/G ATF6 genotype and an increased risk of type 2 diabetes in people with obesity or overweight, regardless of known dietary risk factors. Further research is needed to support the potential of silencing the ATF6 gene as a means for the treatment and prevention of type 2 diabetes.

Cannabigerol as an anti-inflammatory agent altering the level of arachidonic acid derivatives in the colon tissue of rats subjected to a high-fat high-sucrose diet

Fat and sugar overconsumption is the cause of increasing worldwide incidence of gastrointestinal tract in inflammatory conditions. The intestinal pre-inflammatory alterations are partially reversible, simultaneously inhibiting the predisposition to colitis. Searching for an effective pharmacotherapy for treating inflammatory conditions in the intestine is essential. This study aimed to investigate the effect of cannabigerol (CBG) on the inflammation state in the colon tissue of rats subjected to high-caloric diet. The experiment was conducted on male Wistar rats subjected to a standard or a high-fat high-sucrose diets for six weeks. For the last 14 days, half of rats from both groups received intragastrically cannabigerol solution (30 mg/kg of body mass). The ratio of n-6/n-3 PUFA, the activity of n-6 and n-3 PUFA, and arachidonic acid (AA) content in selected lipid fractions were determined by gas-liquid chromatography. Immunoblotting examined the expression of proteins involved in inflammation development. ELISA kits measured the content of arachidonic acid derivatives. CBG treatment reduced the n-6/n-3 PUFA ratio in TAG fraction and increased the n-3 PUFA pathway activity in almost all lipid fractions. Cannabigerol supplementation decreased AA concentration in PL and TAG. CBG also caused diminishments in the expression of cPLA2, COX-1, COX-2, and 12/15-LOX, which was indirectly correlated with a decreased LTB4 level and an increased LXA4 level. We concluded that cannabigerol has a protective influence on the development of inflammation in the colon tissue under lipid and sugar overload condition, thereby favoring cancer initiation and progression.

The impact of consuming different types of high-caloric fat diet on the metabolic status, liver, and aortic integrity in rats

Consumption of high-caloric diets contributes to the alarming number of overweight and obese individuals worldwide, which in turn leads to several diseases and multiple organ dysfunction. Not only has the number of calories taken per day but also the type of fat in the diet has an important impact on health. Accordingly, the purpose of the current study was to examine the impact of different types of high-caloric fat diets on the metabolic status and the integrity of the liver and aorta in albino rats. Adult male albino rats were divided into 6 groups: Control group, long chain-saturated fat group (SFD), long chain-monounsaturated fat (MUFAs) group, long chain-polyunsaturated fat (PUFAs) group, medium-chain fat (MCFAs) group, and short-chain fat (SCFAs) group. Body mass index (BMI), Lee index, and visceral fat amount were reported. Serum levels of insulin, liver transaminases, lipid profile, and different oxidative stress and inflammatory markers were evaluated. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), and adiponectin/leptin ratio were also calculated. Histopathological examinations of liver and aorta with Masson’s trichrome stain, and immune-staining for Nuclear Factor Erythroid-2-Related Factor-2 (Nrf2) were also done. SFD group showed significantly elevated liver transaminases, inflammatory markers, HOMA-IR, dyslipidemia, reduced adiponectin, and deficient anti-oxidative response compared to other groups together with disturbed hepatic and aortic architecture. Other treated groups showed an improvement. PUFAs group showed the highest level of improvement. Not all high-fat diets are hazardous. Diets rich in PUFAs, MUFAs, MCFAs, or SCFAs may protect against the hazards of high caloric diet.

The dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonist tirzepatide effects on body weight evolution, adiponectin, insulin and leptin levels in the combination of obesity, type 2 diabetes and menopause in mice.

Tirzepatide (Tzp), a novel dual agonist glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1, is approved for treating insulin resistance and obesity, and menopausal women consuming a high-calorie diet are a target to study the Tzp effect. Therefore, we aimed to allometrically scale body weight (BW) in Tzp-treated obese diabetic menopausal mice. Three-month-old C57BL/6 female mice had bilateral ovariectomy (Ovx) or a sham procedure and for 12 weeks were fed a control diet or a high-fat and high sucrose diet (n = 120/each group [control (C), obese diabetic (Od), Ovx (O), sham (S), Tzp (T)]). Tzp was subcutaneously administered (10 nmol/kg) or vehicle once a day for an additional 4 weeks. The analysis considered log-transformed data and the allometric equation log y = log a + b log x. Od and OdO showed more upward slopes than C and CO. In C, BW was non-allometric by T administration. Od and OdO showed slightly positive slopes (more prominent in OdO than Od). OdT and OdOT showed negative slopes, significant intercepts, and more robust Pearson coefficients than untreated ones. A potent drug effect was seen with BW allometric decline. Interactions between diet versus Ovx and diet versus Tzp affected weight gain. Diet versus Ovx versus Tzp affected food intake. A model was developed to show three usual factors observed in mature women. Notably, Tzp improved the metabolism and weight loss of OdO mice. Tzp-treated mice showed negative allometric BW across treatment time, which is a quantitative assessment that allows better comparison between results.

Effect of Bidens tripartita leaf supplementation on the organism of rats fed a hypercaloric diet high in fat and fructose

Herbs play an important role in folk medicine, and scientific research has confirmed the properties of their use as an alternative treatment, including the treatment and mild correction of metabolic disorders during disease. Trifid bur-marigold (Bidens tripartita) is a pharmacopoeial herbal raw material that is widely used in clinical practice as an external remedy for skin lesions and as an internal remedy for digestive and respiratory disorders. In this work, the general effect of dried leaves of B. tripartita on physiological activity and metabolic processes in model animals on a high-calorie diet was determined. For the experiment, three groups of 18 male white laboratory rats were formed and fed a hypercaloric diet (increased fat content and 20% fructose solution instead of water) for 27 days, in addition to 0.4% and 4.0% dried leaves of B. tripartita. The consumption of 0.4% and 4.0% of the medicinal plant resulted in a significant delay in the body weight gain and the average daily weight gain of the rats compared to the control group. Dried leaves of B. tripartita in the diet of rats decreased the relative weight of the thymus and increased the relative weight of the brain, and at a dose of 4.0%, increased the relative weight of the lungs and individual large intestines (cecum and colon). Dietary supplementation with B. tripartita caused an increase in globulin concentration and changes in protein coefficient. Blood parameters such as: urea, urea nitrogen, inorganic phosphorus, glucose and bilirubin levels changed depending on the dose. In the general blood test, consumption of dried leaves of B. tripartita caused a decrease in hematocrit, hemoglobin concentration and platelet count, but increased the number of eosinophils. Bidens tripartita at both concentrations significantly increased ALT activity with a corresponding change in the blood De Ritis ratio. The addition of 20 g of B. tripartita leaves to the diet increased alkaline phosphatase activity and decreased alpha-amylase activity, while 200 g increased blood gamma-glutamyltransferase activity. At the end of the experiment, the rats' orientation activity, determined in the open field, changed according to the herb dose consumed: 0.4% leaves caused an increase and 4.0% a decrease. Physical activity was reduced and emotional state increased, regardless of the dose of dried B. tripartita leaves, compared to the control group of animals. The results obtained show that the addition of B. tripartita dried leaves as a dietary supplement to a high-calorie diet is safe, does not cause pathological changes or side effects, and has a significant effect on metabolic processes. This provides theoretical support for the use of B. tripartita dried leaves in the manufacture of nutraceutical and pharmacological products for the correction of metabolic disorders in humans and animals. The doses and duration of their application require further studies.