Hepatic Effects of Low-Carbohydrate Diet Associated with Different Lipid Sources: Insights into Oxidative Stress, Cytotoxicity, and Epigenetic Markers in a mouse Model of Obesity.

BACKGROUND: Low-carbohydrate and high-fat diet (LCHF) models have been widely explored as alternatives for treating obesity and promoting weight loss. Their effect is attributed to the change in energy substrate that stimulates ketogenic pathways that can metabolically overload the liver. However, little has been studied about the impact of lipid sources prioritized in the LCHF diet. OBJECTIVES: This study aims to evaluate the impact of different fat sources in the LCHF diet on markers of liver injury, oxidative stress, and epigenetics in obesity. METHODS: Adult male mice were initially induced to obesity by a high-fat and high-sugar diet for 10 wk. Subsequently, they underwent a weight-loss treatment intervention involving an LCHF diet with various sources of fats, including saturated, omega-3 (ω-3) (n-3), omega-6 (ω-6) (n-6), and omega-9 (ω-9) (n-9). At the end of the treatment, markers of liver injury, oxidative stress, and epigenetics were evaluated. RESULTS: The LCHF diet was effective in inducing weight loss. However, unsaturated lipid sources (omegas) exhibited superior outcomes. Specifically, the ω-9 group displayed diminished oxidative stress concentrations and decreased markers of liver injury. The ω-3 group demonstrated efficacy in modulating epigenetic markers, thereby reducing oxidative stress, mutagenicity, and markers of liver injury. Correlation tests demonstrated that there was an interaction between the activity of antioxidants and epigenetic enzymes. CONCLUSIONS: Our results suggest that LCHF diets associated with ω-3 and ω-9 have the potential for weight loss and liver health recovery in obesity through antioxidant and epigenetic mechanisms.

Maternal preconception glucose intolerance and fatty acid intake from conception to weaning: impact on offspring energy homeostasis in both male and female.

Environmental factors in the early life stages can lead the descendant to adaptations in gene expression, permanently impacting several structures and organs. The amount and quality of fatty acids in the maternal diet in pregnancy and lactation were found to impact offspring metabolism. So, maternal diet and insulin resistance can affect the male and female descendants through distinct pathways and at different time points. We hypothesized that maternal high-fat diet (HFD) intake before conception and an adequate amount of different fatty acids intake during pregnancy and lactation could influence the energy homeostasis system of 21-day-old offspring. Female rats received control diet (C) or HFD (HF) for 8 weeks before pregnancy. During pregnancy and lactation C group remained with same diet (C-C), HF group were distributed into 4 groups and received C diet (HF-C), normolipidic diet based on saturated fatty acids (HF-S) or based on polyunsaturated fatty acids n-3 (HF-P) or remained in same diet (HF-HF). Maternal HFD in preconception, pregnancy, and lactation (HF-HF) led to lower glucagon-like peptide-1 levels in male (HF-HF21) compared to other groups (C-C21, HF-C21, and HF-P21) and compared to HF-HF21 females. Neuropeptide YY levels were higher in the HF-HF21, HF-C21, and HF-S21 male offspring compared to HF-P21. HF-P21 was similar to C-C21. Positive correlations were found among the energy homeostasis markers genes expressed in the offspring hypothalamus. Maternal diet changes to adequate quantities of fatty acids during pregnancy and lactation showed less impaired results but was not entirely avoided. A maternal diet based on PUFA n-3 during pregnancy and lactation seems to reverse the damage of an HFD in preconception. These results of homeostasis energy system disturbance in the offspring at weaning give us clues about changes that precede the onset of the disease in adult life - adding notes to the knowledge for future investigations of prevention and treatment of chronic diseases.

Obesity-related inflammatory modulation by juçara berry (Euterpe edulis Mart.) supplementation in Brazilian adults: a double-blind randomized controlled trial.

PURPOSE: Obesity is an inflammatory-related disease, which recruits immune system cells triggering to imbalanced production of cytokines. Obesity management and treatment using foods bioactive compounds have gained clinical and scientific relevance. Juçara (Euterpe edulis Mart.) fruit is rich in fibers, unsaturated lipids and, anthocyanins showing potential health benefits. Thus, we investigated the effect of juçara pulp intake on inflammatory status of monocytes from obese individuals. METHODS: It is a placebo-controlled, randomized double-blind trial. Twenty-seven obese participants (BMI between 30.0 and 39.9 kg/m2) of both genders from 31 to 59-year-old, divided into two groups: 5 g juçara freeze-dried pulp or 5 g of placebo for 6 weeks. Before and after supplementation, blood samples were collected and monocytes obtained and stimulated with lipopolysaccharides. After 24 h of incubation, the cells and supernatants were analyzed. RESULTS: Post-treatment, juçara reduced TLR4, and IL-6 mRNA compared to placebo. Juçara also increased IL-10 mRNA in post-treatment. The protein expression of TLR4 pathway post-treatment, MYD88 expression reduced in juçara group compared to placebo. The juçara post-treatment reduced pIKKα/ß compared to the placebo. Ob-R protein levels were higher in the juçara group post-treatment compared to pre-treatment. IL-6, TNF-α, and MCP-1 production by monocytes were reduced by juçara in post-treatment compared to pre-treatment levels. The supplementation increased IL-10 in juçara group with LPS compared to pre-treatment and versus juçara group without LPS. CONCLUSION: These results demonstrated a proinflammatory state at the beginning, which was improved by juçara pulp consumption. Our results suggest juçara pulp as a potential tool against the proinflammatory status of obesity.

Prebiotic potencial of juçara berry on changes in gut bacteria and acetate of individuals with obesity.

PURPOSE: Whole plant foods can be fermentable by SCFA-producing bacteria and positively influence host adipose tissue development and obesity related-metabolic disorders, conferring a prebiotic role. Considering the juçara berry composition, rich in fiber and polyphenols, we hypothesized the probable prebiotic role of juçara in individuals with obesity. METHODS: It was a randomized double-blind placebo-controlled trial with 35 volunteers with obesity I and II of both sexes aged from 31 to 59 years, divided into juçara group (5 g lyophilized juçara) or placebo group (5 g of maltodextrin) for 6 weeks. Before and after supplementation, food intake and blood and stool samples were collected to evaluate serum LPS, SCFA, and microbial bacteria. RESULTS: Significant increase in fecal acetate (g = 0.809; p = 0.038) and in relative abundance of A. muciniphila, Bifidobacterium spp. and C. coccoides were observed in response to juçara supplementation (Δ% = 239.6%, 182.6%, and 214%, respectively), with a significant mediator role of Bifidobacterium spp. in high amounts of fecal acetate (z = 2.925; p = 0.003). To certify the prebiotic role of juçara, the averages were adjusted for total fiber intake; and there was no effect of the fiber intake on the SCFA nor on the intestinal bacteria. CONCLUSION: Juçara berry may haveprebiotic function, with emphasis on the bifidogenic effect, leading to increased excretion of acetate.

The protective effect of grape skin or purple carrot extracts against cadmium intoxication in kidney of rats.

The aim of this study was to evaluate the protective effect of grape skin or purple carrot extracts against cadmium-induced intoxication in rats' kidneys. For this purpose, 30 male Wistar rats were distributed into six groups (n = 5), as follows: control group; cadmium group and groups treated with grape skin at 175 or 350 mg / L doses; or purple carrot extract at 400 mg / L or 800 mg / L doses, by drinking water. In the group exposed to cadmium, histopathological analysis revealed severe tissue injury as a result of coagulation necrosis, congested vessels and inflammatory infiltrate. Animals treated with grape skin or purple carrot extracts improved the histopathological changes induced by cadmium. 8-OHdG immunoexpression and catalase gene expression decreased in rats treated with purple carrot or grape skin extracts. Grape skin extract was able to increase SOD-CuZn gene expression as well. Toll-like signaling pathway (TLR2, PIKK and TRAF6) and cytochrome c expressions were not altered after the treatment with grape skin or purple carrot extracts. Taken together, we conclude that grape skin and purple carrot extracts had a protective effect on the rats' kidneys after cadmium intoxication, by means of tissue regenerating tissue regeneration and antioxidant properties, grape skin extract being more effective for this purpose.

Polyphenols-Rich Fruit (Euterpe edulis Mart.) Prevents Peripheral Inflammatory Pathway Activation by the Short-Term High-Fat Diet.

Juçara berry is a potential inflammatory modulator, rich in dietary fiber, fatty acids, and anthocyanins. Considering this, we evaluated the high-fat diet (HFD) intake supplemented with different doses of freeze-dried juçara pulp on the TLR4 pathway. Twenty-seven male Wistar rats with ad libitum access to food and water were divided into four experimental groups: control standard chow group (C); high-fat diet control group (HFC); high-fat diet juçara 0.25% group (HFJ0.25%); and high-fat diet juçara 0.5% group (HFJ0.5%). The inflammatory parameters were analyzed by ELISA and Western blotting in liver and retroperitoneal adipose tissue (RET). The HFJ0.25% group had the energy intake, aspartate transaminase (AST) levels, and liver triacylglycerol accumulation reduced; also, the tumor necrosis factor α (TNF-α) and TNF receptor-associated factor 6 (TRAF6) expression in RET were reduced. However, there were no changes in other protein expressions in liver and adipose tissue. Adiposity and pNFκBp50 had a positive correlation in HFC and HFJ0.5%, but not in the C group and HFJ0.25%. The necrosis hepatic score did not change with treatment; however, the serum (AST) levels and the hepatic triacylglycerol were increased in HFC and HFJ0.5%. These results demonstrated that one week of HFD intake triggered pro-inflammatory mechanisms and liver injury. Additionally, 0.25% juçara prevented inflammatory pathway activation, body weight gain, and liver damage.

The Use of Juçara (Euterpe edulis Mart.) Supplementation for Suppression of NF-κB Pathway in the Hypothalamus after High-Fat Diet in Wistar Rats.

Obesity is associated with modern diets that are rich in saturated fatty acids. These dietary patterns are linked to low-grade proinflammatory mechanisms, such as the toll-like receptor 4/nuclear factor kappa-B (NF-κB) pathway rapidly activated through high-fat diets. Juçara is a berry rich in anthocyanins and unsaturated fatty acids, which prevents obesity and associated comorbidities. We evaluated the effect of different doses of freeze-dried juçara pulp on NF-κB pathway after the consumption of short-term high-fat diet. Male Wistar rats with ad libitum access to food and water were divided into four groups: Control diet (C), high-fat diet (HFC), high-fat diet with 0.25% juçara (HFJ 0.25%), and high-fat diet with 0.5% juçara (HFJ 0.5%). Energy intake and body weight gain were increased in HFC and HFJ 0.5% groups compared to C group. The hypothalamus weight reduced in the HFC group compared to C and HFJ 0.25% groups. Cytokines, MYD88, TRAF6, and pNF-κBp50 levels in the hypothalamus, serum triacylglycerol, LDL-cholesterol (LDL-C), and free fatty acid levels were improved in the HFJ 0.25% group. In summary, the HFJ 0.25% group had better protective effects than those in the HFJ 0.5%. Therefore, 0.25% juçara can be used to protect against central inflammation through the high-fat diet-induced NF-κB pathway.

Effects of prebiotic supplementation on the expression of proteins regulating iron absorption in anaemic growing rats.

Prebiotics may increase intestinal Fe absorption in anaemic growing rats. The present study evaluated the effects of high-performance (HP) inulin and oligofructose on factors that regulate Fe absorption in anaemic rats during the growth phase. Male Wistar rats aged 21 d of age were fed AIN-93G ration without Fe for 2 weeks to induce Fe-deficiency anaemia. The rats were fed on day 35 a control diet, or a diet with 10 % HP inulin, or a diet with 10 % oligofructose, without Fe supplementation. The animals were euthanised after 2 weeks, and segments of the duodenum, caecum, colon and liver were removed. The expression levels of proteins in the intestinal segments were assessed using Western blotting. The levels of serum, urine and liver hepcidin and the concentrations of IL-10, IL-6 and TNF-α in the caecum, colon and liver were measured using the ELISA test. HP inulin increased the expression of the divalent metal transporter 1 protein in the caecum by 162 % (P= 0·04), and the expression of duodenal cytochrome b reductase in the colon by 136 % (P= 0·02). Oligofructose decreased the expression of the protein ferroportin in the duodenum (P= 0·02), the concentrations of IL-10 (P= 0·044), IL-6 (P= 0·036) and TNF-α (P= 0·004) in the caecum, as well as the level of urinary hepcidin (P< 0·001). These results indicate that prebiotics may interfere with the expression of various intestinal proteins and systemic factors involved in the regulation of intestinal Fe absorption in anaemic rats during the growth phase.

Oligofructose supplementation during pregnancy and lactation impairs offspring development and alters the intestinal properties of 21-d-old pups.

BACKGROUND: Previously, we showed that the intake of trans fatty acids during pregnancy and lactation triggers a pro-inflammatory status in the offspring. On the other hand, prebiotics can alter the intestinal environment, reducing serum lipopolysaccharides (LPS) concentrations. This study evaluated the effect of the oligofructose 10% diet supplementation in the presence or absence of hydrogenated vegetable fat during pregnancy and lactation on the development, endotoxemia and bacterial composition of 21-d-old offspring. METHODS: On the first day of pregnancy rats were divided into four groups: control diet (C), control diet supplemented with 10% oligofructose (CF), diet enriched with hydrogenated vegetable fat, rich in TFA (T) or diet enriched with hydrogenated vegetable fat supplemented with 10% oligofructose (TF). Diets were maintained during pregnancy and lactation. At birth, 7th, 14th and 21th, pups were weighed and length was measured. Serum concentrations of LPS and free fatty acids (FFA) were performed by specific kits. Bacterial DNA present in faeces was determined by real-time PCR. Data were expressed as mean ± standard error of the mean and the statistical analysis was realized by ANOVA two-way and ANOVA for repeated measures. p < 0.05 was considered significant. RESULTS: We observed that the oligofructose (10%) supplementation during pregnancy and lactation reduced body weight, body weight gain, length and serum FFA in the CF and TF group compared to C and T group respectively, of the 21-day-old offspring, accompanied by an increase in serum LPS and genomic DNA levels of lactobacillus spp. on faeces of the CF group in relation to C group. CONCLUSION: In conclusion, dam's diet supplementation with 10% of oligofructose during pregnancy and lactation, independent of addition with hydrogenated vegetable fat, harms the offspring development, alters the bacterial composition and increases the serum concentrations of lipopolysaccharides in 21d-old pups.

Role of training and detraining on inflammatory and metabolic profile in infarcted rats: influences of cardiovascular autonomic nervous system.

The aim of this study was to evaluate the effects of exercise training (ET, 50-70% of VO2 max, 5 days/week) and detraining (DT) on inflammatory and metabolic profile after myocardial infarction (MI) in rats. Male Wistar rats were divided into control (C, n = 8), sedentary infarcted (SI, n = 9), trained infarcted (TI, n = 10; 3 months of ET), and detrained infarcted (DI, n = 11; 2 months of ET + 1 month of DT). After ET and DT protocols, ventricular function and inflammation, cardiovascular autonomic modulation (spectral analysis), and adipose tissue inflammation and lipolytic pathway were evaluated. ET after MI improved cardiac and vascular autonomic modulation, and these benefits were correlated with reduced inflammatory cytokines on the heart and adipose tissue. These positive changes were sustained even after 1 month of detraining. No expressive changes were observed in oxidative stress and lipolytic pathway in experimental groups. In conclusion, our results strongly suggest that the autonomic improvement promoted by ET, and maintained even after the detraining period, was associated with reduced inflammatory profile in the left ventricle and adipose tissue of rats subjected to MI. These data encourage enhancing cardiovascular autonomic function as a therapeutic strategy for the treatment of inflammatory process triggered by MI.

Preventive effects of chitosan coacervate whey protein on body composition and immunometabolic aspect in obese mice.

UNLABELLED: Functional foods containing bioactive compounds of whey may play an important role in prevention and treatment of obesity. The aim of this study was to investigate the prospects of the biotechnological process of coacervation of whey proteins (CWP) in chitosan and test its antiobesogenic potential. METHODS: CWP (100 mg · kg · day) was administered in mice with diet-induced obesity for 8 weeks. The animals were divided into four groups: control normocaloric diet gavage with water (C) or coacervate (C-CWP), and high fat diet gavage with water (HF) or coacervate (HF-CWP). RESULTS: HF-CWP reduced weight gain and serum lipid fractions and displayed reduced adiposity and insulin. Adiponectin was significantly higher in HF-CWP group when compared to the HF. The level of LPS in HF-W group was significantly higher when compared to HF-CWP. The IL-10 showed an inverse correlation between the levels of insulin and glucose in the mesenteric adipose tissue in the HF-CWP group. CWP promoted an increase in both phosphorylation AMPK and the amount of ATGL in the mesenteric adipose tissue in HF-CWP group. CONCLUSION: CWP was able to modulate effects, possibly due to its high biological value of proteins. We observed a protective effect against obesity and improved the inflammatory milieu of white adipose tissue.

Maternal dietary fatty acid composition and content prior to and during pregnancy and lactation influences serum profile, liver phenotype and hepatic miRNA expression in young male and female offspring.

This study aimed to investigate whether modifying the pre-gestational lipid content could mitigate metabolic damage in offspring from dams exposed to a high-fat (HF) diet before conception and during pregnancy and lactation, with a focus on sex-specific outcomes. Specific effects of maternal normolipidic diets on offspring were also assessed. Female Wistar rats received control (C) or HF diets before conception. During pregnancy and lactation, females were distributed in five groups: C-C, HF-HF, HF-C, HF-saturated (HF-S) or HF-polyunsaturated n-3 group (HF-P). Saturated and PUFA n-3 diets were normolipidic. In 21-day-old offspring, corporal parameters, adiposity, serum metabolites, OGTT, liver phenotype, and miR-34a-5p hepatic expression were determined. Pre-gestational HF diet impaired glycemic response in females, independent of any change in body weight. Female and male offspring from dams continuously exposed to HF diet exhibited hyperglycemia, increased adiposity, and disrupted serum lipid profiles. Male offspring showed increased hepatic fat accumulation and miR-34a-5p expression. Shifting maternal dietary lipid content to normolipidic diets restored offspring's phenotype; however, decreased SIRT1, IRß and IRS1 expression in offspring from dams exposed to HF diet before conception suggested early indicators of glucose metabolism damage. Our findings indicated a pronounced metabolic impact on males. In conclusion, glucose tolerance impairment in females before conception disturbed intrauterine environment, influencing in offspring's phenotype. Modifying maternal dietary lipid content mitigated effects of pre-gestational HF diet exposure on young offspring. Nevertheless, decreased hepatic levels of critical insulin signaling proteins indicated that independently of the maternal diet, pre-existing HF diet-induced glucose intolerance before conception may adversely program the offspring's phenotype.

Nutraceutical composition (yeast ß-glucan, prebiotics, minerals, and silymarin) predicts improvement of sleep quality and metabolic parameters: A randomized pilot study.

BACKGROUND & AIMS: The search for integrative and natural therapies that favor homeostasis to boost sleep and diet quality took place for young adult populations as a non-pharmacological strategy for long-term good quality of life. Thus, the present pilot study aims to investigate the effects of 90-day consumption of a nutraceutical composition on the neuro-immune-endocrine axis, providing better sleep quality and health improvement. METHODS: For this, from March 2021 to June 2021, twenty-two Brazilian young adult volunteers (women and men) with BMI between 18.5 and 34.9 kg/m2 were divided into three distinct supplementation groups: NSupple; NSupple plus_S, and NSupple plus. Briefly, the supplement compositions included yeast ß-glucan, prebiotics, and minerals in different concentrations associated or not with the herbal medicine silymarin. Neither nutritional nor physical activity interventions were performed during this pilot study period. The anthropometrics measures, questionnaires answer data, and harvest blood for metabolic, inflammatory, and hormonal tests were collected at baseline time (day zero-T0) and day 90 (T90) post-supplementation. RESULTS: Our results highlight that the supplementation reduced body mass index (BMI), Waist-to-height ratio (WHtR), waist circumference, AST/ALT ratio, alkaline phosphatase, and HbA1c. Post-supplementation the IL-6 and IL-10 levels and the sleep, humor, and quality of life scores were suggested to improve. Sleep quality improvement seems to predict the reduction of adiposity-related body measures. CONCLUSION: In sum, the nutraceutical supplementation might be related to anthropometric, metabolic, and endocrine parameters after 90 days reflecting on perception of humor, sleep, and life quality enhancement. However, it is important to recognize the limitation of the data presented considering that this was a pilot study. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT04810572 registered on 20th February 2021.

Nutraceutical Capsules LL1 and Silymarin Supplementation Act on Mood and Sleep Quality Perception by Microbiota-Gut-Brain Axis: A Pilot Clinical Study.

Stress, unhealthy lifestyle, and sleep disturbance worsen cognitive function in mood disorders, prompting a rise in the development of integrative health approaches. The recent investigations in the gut-brain axis field highlight the strong interplay among microbiota, inflammation, and mental health. Thus, this study aimed to investigate a new nutraceutical formulation comprising prebiotics, minerals, and silymarin's impact on microbiota, inflammation, mood, and sleep quality. The study evaluated the LL1 + silymarin capsule supplementation over 180 days in overweight adults. We analyzed the fecal gut microbiota using partial 16S rRNA sequences, measured cytokine expression via CBA, collected anthropometric data, quality of life, and sleep questionnaire responses, and obtained plasma samples for metabolic and hormonal analysis at baseline (T0) and 180 days (T180) post-supplementation. Our findings revealed significant reshaping in gut microbiota composition at the phylum, genus, and species levels, especially in the butyrate-producer bacteria post-supplementation. These changes in gut microbiota were linked to enhancements in sleep quality, mood perception, cytokine expression, and anthropometric measures which microbiota-derived short-chain fatty acids might enhance. The supplementation tested in this study seems to be able to improve microbiota composition, reflecting anthropometrics and inflammation, as well as sleep quality and mood improvement.

Modulation of the gut microbiome and Firmicutes phylum reduction by a nutraceutical blend in the obesity mouse model and overweight humans: A double-blind clinical trial.

Overweight and obesity are closely linked to gut dysbiosis/dysmetabolism and disrupted De-Ritis ratio [aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio], which may contribute to chronic noncommunicable diseases onset. Concurrently, extensive research explores nutraceuticals, and health-enhancing supplements, for disease prevention or treatment. Thus, sedentary overweight volunteers were double-blind randomized into two groups: Novel Nutraceutical_(S) (without silymarin) and Novel Nutraceutical (with silymarin). Experimental formulations were orally administered twice daily over 180 consecutive days. We evaluated fecal gut microbiota, based on partial 16S rRNA sequences, biochemistry and endocrine markers, steatosis biomarker (AST/ALT ratio), and anthropometric parameters. Post-supplementation, only the Novel Nutraceutical group reduced Clostridium clostridioforme (Firmicutes), Firmicutes/Bacteroidetes ratio (F/B ratio), and De-Ritis ratio, while elevating Bacteroides caccae and Bacteroides uniformis (Bacteroidetes) in Brazilian sedentary overweight volunteers after 180 days. In summary, the results presented here allow us to suggest the gut microbiota as the action mechanism of the Novel Nutraceutical promoting metabolic hepatic recovery in obesity/overweight non-drug interventions.

Nutraceutical blends predict enhanced health via microbiota reshaping improving cytokines and life quality: a Brazilian double-blind randomized trial.

Nutraceutical interventions supporting microbiota and eliciting clinical improvements in metabolic diseases have grown significantly. Chronic stress, gut dysbiosis, and metainflammation have emerged as key factors intertwined with sleep disorders, consequently exacerbating the decline in quality of life. This study aimed to assess the effects of two nutraceutical formulations containing prebiotics (fructooligosaccharides (FOS), galactooligosaccharides (GOS), yeast ß-glucans), minerals (Mg, Se, Zn), and the herbal medicine Silybum marianum L. Gaertn., Asteraceae (Milk thistle or Silymarin). These formulations, namely NSupple (without silymarin) and NSupple_Silybum (with silymarin) were tested over 180 days in overweight/obese volunteers from Brazil's southeastern region. We accessed fecal gut microbiota by partial 16S rRNA sequences; cytokines expression by CBA; anthropometrics, quality of life and sleep, as well as metabolic and hormonal parameters, at baseline (T0) and 180 days (T180) post-supplementation. Results demonstrated gut microbiota reshaping at phyla, genera, and species level post-supplementation. The Bacteroidetes phylum, Bacteroides, and Prevotella genera were positively modulated especially in the NSupple_Silybum group. Gut microbiota modulation was associated with improved sleep patterns, quality-of-life perception, cytokines expression, and anthropometric parameters post-supplementation. Our findings suggest that the nutraceutical blends positively enhance cardiometabolic and inflammatory markers. Particularly, NSupple_Silybum modulated microbiota composition, underscoring its potential significance in ameliorating metabolic dysregulation. Clinical trial registry number: NCT04810572. 23/03/2021.

Parental High-Fat High-Sugar Diet Intake Programming Inflammatory and Oxidative Parameters of Reproductive Health in Male Offspring.

Parental nutrition can impact the health of future generations, programming the offspring for the development of diseases. The developing germ cells of the offspring could be damaged by the maternal or the paternal environment. The germ cells in development and their function could be affected by nutritional adversity and therefore, harm the health of subsequent generations. The paternal or maternal intake of high-fat diets has been shown to affect the reproductive health of male offspring, leading to imbalance in hypothalamic-pituitary-gonadal axis, testicular oxidative stress, low testosterone production, and changes in sperm count, viability, motility, and morphology. There is a need for studies that address the combined effects of diets with a high-fat and high-sugar (H) content by both progenitors on male reproduction. In this context, our study evaluated epigenetic parameters and the inflammatory response that could be associated to oxidative stress in testis and epididymis of adult offspring. 90 days-old male rats were divided according to the combination of the parental diet: CD (control paternal and maternal diet), HP (H paternal diet and control maternal diet), HM (H maternal diet and control paternal diet) and HPM (H paternal and maternal diet).We evaluated serum levels of testosterone and FSH; testicular gene expression of steroidogenic enzymes Star and Hsd17b3 and epigenetic markers Dnmt1, Dnmt3a, Dnmt3b, and Mecp2; testicular and epididymal levels of TNF-α, IL-6, IL-10, and IL-1ß; testicular and epididymal activity of SOD, CAT, and GST; the oxidative markers MDA and CP; the daily sperm production, sperm transit time, and sperm morphology. Testicular epigenetic parameter, inflammatory response, oxidative balance, and daily sperm production of the offspring were affected by the maternal diet; paternal diet influenced serum testosterone levels, and lower daily sperm production was exacerbated by the interaction effect of both parental intake of high-fat high-sugar diet in the testis. There was isolated maternal and paternal effect in the antioxidant enzyme activity in the cauda epididymis, and an interaction effect of both parents in protein oxidative marker. Maternal effect could also be observed in cytokine production of cauda epididymis, and no morphological effects were observed in the sperm. The potential programming effects of isolated or combined intake of a high-fat high-sugar diet by the progenitors could be observed at a molecular level in the reproductive health of male offspring in early adulthood.

Novel nutraceutical supplements with yeast ß-glucan, prebiotics, minerals, and Silybum marianum (silymarin) ameliorate obesity-related metabolic and clinical parameters: A double-blind randomized trial.

Purpose: It is known that obesity has a multifactorial etiology that involves genetic and environmental factors. The WHO estimates the worldwide prevalence of 1.9 billion overweight adults and more than 650 million people with obesity. These alarming data highlight the high and growing prevalence of obesity and represent a risk factor for the development and aggravation of other chronic diseases, such as nonalcoholic fatty liver disease (NAFLD) that is frequently considered the hepatic outcome of type 2 diabetes. The use of non-pharmacological therapies such as food supplements, nutraceuticals, and natural integrative therapies has grown as an alternative tool for obesity-related diseases compared to conventional medications. However, it is a still little explored research field and lacks scientific evidence of therapeutic effectiveness. Considering this, the aim is to evaluate whether a new nutraceutical supplement composition can improve and supply essential mineral nutrients, providing an improvement of obesity-related metabolic and endocrine parameters. Methods: Sedentary volunteers (women and men) with body mass index (BMI) ≤34.9 kg/m2 were divided into two groups: Novel Nutraceutical Supplement_(S) (n = 30) and Novel Nutraceutical Supplement (n = 29), differing in the absence (S) or presence of silymarin, respectively. Volunteers were instructed to take two capsules in the morning and two capsules in the evening. No nutritional intervention was performed during the study period. The data (anthropometrics and anamneses) and harvest blood (biochemistry and hormonal exams) were collected at three different time points: baseline time [day 0 (T0)], day 90 (T90), and day 180 (T180) post-supplementation. Results: In the anthropometric analysis, the waist circumference in middle abdomen (WC-mid) and waist circumference in iliac crest (WC-IC) were reduced. Also, the waist-to-height ratio (WHt R) and waist-to-hip ratio (WHR) seem to slightly decrease alongside the supplementation period with both nutraceutical supplements tested as well as transaminase enzyme ratio [aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AAR)], a known as a biomarker of NAFLD, and endocrine hormones cortisol and thyroid-stimulating hormone (TSH) at 90 and 180 days post-supplementation. Conclusions: In a condition associated with sedentary and no nutritional intervention, the new nutraceutical supplement composition demonstrated the ability to be a strong and newfangled tool to improve important biomarkers associated with obesity and its comorbidities.

The Symbiotic Effect of a New Nutraceutical with Yeast ß-Glucan, Prebiotics, Minerals, and Silybum marianum (Silymarin) for Recovering Metabolic Homeostasis via Pgc-1α, Il-6, and Il-10 Gene Expression in a Type-2 Diabetes Obesity Model.

The use of natural products and derivatives for the prevention and control of non-communicable chronic diseases, such as type-2 diabetes (T2D), obesity, and hepatic steatosis is a way to achieve homeostasis through different metabolic pathways. Thus, male C57BL/6 mice were divided into the following groups: high-fat diet (HFD) vehicle, HFD + Supplemented, HFD + Supplemented_S, and isolated compounds. The vehicle and experimental formulations were administered orally by gavage once a day over the four weeks of the diet (28 consecutive days). We evaluated the energy homeostasis, cytokines, and mitochondrial gene expression in these groups of mice. After four weeks of supplementation, only the new nutraceutical group (HFD + Supplemented) experienced reduced fasting glycemia, insulin, HOMA index, HOMA-ß, dyslipidemia, ectopic fat deposition, and hepatic fibrosis levels. Additionally, the PPARγ coactivator 1 α (Pgc-1α), interleukin-6 (Il-6), and interleukin-10 (Il-10) gene expression were augmented, while hepatic steatosis decreased and liver parenchyma was recovered. The glutathione-S-transferase activity status was found to be modulated by the supplement. We discovered that the new nutraceutical was able to improve insulin resistance and hepatic steatosis mainly by regulating IL-6, IL-10, and Pgc-1α gene expression.

Protective Effect of Grape and Apple Juices against Cadmium Intoxication in the Kidney of Rats.

BACKGROUND: The objective of this study was to evaluate protective effect of grape and apple juices against toxicity induced by cadmium in the kidney of rats. METHODS: A total of 20 male-Wistar rats were distributed into four groups (n=5): Control group: animals received an intraperitoneal (i.p.) injection of 0.9% saline solution and after 15 days, 1 mL of water was administered for 15 days, via gavage; Cadmium group: animals received an intraperitoneal injection of cadmium chloride (1.2 mg/kg) and after 15 days, 1 mL of water was administered for 15 days via gavage; Cadmium+Grape Juice: animals received an i.p. injection of cadmium chloride (1.2 mg/kg), and after 15 days, 0.8 mL of grape juice was administered for 15 days, via gavage; Cadmium+Apple Juice: animals received i.p. injection of cadmium chloride (1.2 mg/kg) and after 15 days, 1.0 mL of apple juice was administered for 15 days, via gavage. RESULTS: Histopathological analysis revealed severe tubular lesion and necrosis in the group exposed to cadmium, while animals exposed to grape or apple juices showed a significant reduction of tissue injury. 8-OHdG immunoexpression, DNA damage, cytochrome C and catalase gene expressions and Toll like signaling pathway (TLR2, and pIKKα/ß) decreased in animals treated with grape juice when compared to cadmium group. CONCLUSION: Taken together, we conclude that grape and apple juices had a protective effect by means of antioxidant, antigenotoxic actions and for promoting tissue regeneration in the kidney of rats following cadmium intoxication.