Improvement Of Metabolism Research Articles

Ketogenic diet as a therapeutic approach in autism spectrum disorder: a narrative review.

The ketogenic diet (KD) originated in the 1920s. It is a dietary model that is low in carbohydrates, adequate in protein, and high in fat content. The diet mimics starvation and increases the production of ketone bodies, leading to ketosis in metabolism. KD is used as an anticonvulsant treatment approach in patients with drug-resistant epilepsy. In addition, it is thought that a KD may have therapeutic potential in the treatment of neurological disorders, including autism spectrum disorders (ASD). Numerous recent studies have demonstrated that a KD can improve behavioural parameters in individuals with ASD. This review aims to address the potential mechanisms of action of the KD and to examine the effects of the KD on individuals diagnosed with ASD. It is likely that this role is mediated through improvements in energy metabolism, reduction of pro-inflammatory cytokine levels, control of neurotransmitters, gene expression and modulation of the gut microbiota. Based on the available evidence, a KD appears to be a safe and effective treatment for ASD.

Effects of Tithonia diversifolia Extract as a Feed Additive on Digestibility and Performance of Hair Lambs

Animal production requires efficiency, safety and environmental sustainability. Bioactive compounds from tropical plants could modulate ruminal fermentation, providing an alternative method to antibiotic treatment and addressing concerns about antibiotic resistance. In this study, the aim was to determine the effects of Tithonia diversifolia extract (TDE) on performance, intake, digestibility and blood parameters [i.e., glucose, blood urea nitrogen (BUN), aspartate aminotransferase (AST), alanine aminotransferase (ALT)] in crossbreed sheep. The main biocompounds of the TDE include caffeic acid (CA), quercetin (QCT), luteolin (LT) and apigenin (AP). Experiment 1: An in vitro dry matter digestibility (IVDMD) study was conducted to determine the optimal inclusion levels. The IVDM values were 73.09a, 82.03b, 81.01b, 73.20a and 74.51a for the control, 5, 10, 15 and 20 g/kg for the DM treatments, respectively (R-Sq adj = 0.857). The levels of 5 and 10 g were selected for the in vivo experiment. Experiment 2: Twenty-eight male crossbred hair lambs were assigned to four treatments (n = 7): control, 20 mg monensin/day, 5 g TDE/day and 10 g TDE/day groups. No differences in animal performance were observed, including body weight and feed conversion (p > 0.05). The TDE at 10 g/day improved NDF digestibility) (61.32%) and reduced the ruminal acetate to propionate ratio. The total digestible nutrients (TDN) were higher in 10 g TDE treatment with 66.41% and the lowest acetate production (67.82%) (p = 0.042), and propionate production (21.07%) were observed. The TDE were safe at 5 g and 10 g/day for liver function and exhibited lower BUN levels suggesting an improvement in protein metabolism. TDE extract at 10 g/day (TDE10), showed improvements in total tract digestibility of NDF and reduced the ruminal acetate to propionate ratio. However, due to TDE10 reducing the DM intake, the improvements in digestibility and ruminal fermentation were not reflected in growth performance improvements.

Mitochondrial metabolic reprogramming of macrophages and T cells enhances CD47 antibody-engineered oncolytic virus antitumor immunity

BackgroundAlthough immunotherapy can reinvigorate immune cells to clear tumors, the response rates are poor in some patients. Here, CD47 antibody-engineered oncolytic viruses (oAd-αCD47) were employed to lyse tumors and activate...

Ellagic acid alleviates high-fructose diet-induced non-alcoholic fatty liver disease by modulating liver metabolic profiles and gut microbiota

This study integrated analyses of gut microbiota and metabolomics to investigate the impact of ellagic acid (EA) on non-alcoholic fatty liver disease (NAFLD). Compared to the high-fructose diet (HFruD) group, the EA group exhibited reduced body weight and fat mass, alongside improvements in blood glucose and lipid metabolism. Liver metabolomics analysis revealed that EA increased the abundance of metabolites in pathways related to unsaturated fatty acids, amino acids and bile acids. Furthermore, EA induced alterations in the composition and structure of gut microbiota, notably decreasing bacterial genera enriched by HFruD while promoting beneficial bacteria such as Faecalibaculum. Correlation analysis demonstrated significant associations among NAFLD markers, gut microbiota and liver metabolites influenced by EA. This study provides new insights into the anti-NAFLD effects of EA, suggesting EA as a promising nutraceutical for improving NAFLD.

The role of exosomes for sustained specific cardiorespiratory and metabolic improvements in males with type 2 diabetes after detraining

BackgroundHigh-intensity interval training (HIIT) has been shown to improve cardiorespiratory fitness (V˙ O2max) but may ameliorate insulin sensitivity only in insulin-resistant humans. It is yet unclear whether these benefits persist after detraining and to which extent duration and effectiveness of metabolic improvements differ between individuals without and with prediabetes or type 2 diabetes (T2D). Understanding these differences is relevant for developing targeted exercise training modes for individuals with different stages of dysglycemia. MethodsMen with (20 T2D) and without T2D (12 insulin-sensitive, IS-NDM; 10 insulin-resistant, IR-NDM) underwent hyperinsulinemic-euglycemic clamps, spiroergometry, ectopic lipid quantification and muscle biopsies at baseline, after 12-week HIIT and after 4-week detraining. FindingsAfter detraining, the HIIT-stimulated V˙ O2max declined in T2D and IR-NDM, but remained higher compared to baseline in all groups. The HIIT-induced changes in hepatic insulin sensitivity and ectopic lipid content were sustained after detraining in T2D and IR-NDM, whereas improvements of whole-body insulin sensitivity were abolished in T2D. T2D and IR-NDM showed persistent increases in the number of small extracellular vesicles, which carry among others antioxidant proteins. The ratio of reduced-to-oxidized glutathione further decreased after detraining in all groups, whereas changes in proteins involved in mitochondrial turnover were dependent on insulin sensitivity, with some evidence for upregulation of fusion and mitophagy in T2D and IR-NDM and upregulation of fission in IS-NDM. Levels of different lipolytic proteins were reduced in all participants after detraining. InterpretationHIIT offers sustained improvement of energy metabolism and hepatic insulin sensitivity in insulin-resistant humans, but long-term adherence is required to maintain these benefits. FundingFunding bodies that contributed to this study are listed in the acknowledgements section.

Metabolic and hepatic phenotypes in sarcopenic obesity and impact of bariatric surgery

Background & AimsSarcopenic obesity (SO) is associated with cardiometabolic disorders and steatotic liver disease and carries major health risks. We assessed the hepatic and metabolic clinical phenotype associated with SO in patients with obesity undergoing bariatric surgery (BS). We also evaluated whether weight-loss and metabolic improvement post-surgery differ between patients with and without SO. Methods972 consecutive patients from a single-center BS cohort who underwent whole-body dual-energy X-ray absorptiometry (DXA) and peri-operative liver biopsy were included. SO was diagnosed using the AIM-SO score, an AI-assisted unbiased clustering algorithm based on body composition. One-year post-surgery, 862 patients were reassessed for AIM-SO score changes. ResultsPre-operatively, 207 (21.3%) patients were diagnosed with SO. These patients had significantly higher prevalence of type-2 diabetes (T2D), arterial hypertension and obstructive sleep apnea (OSA) compared to patients without SO (all p≤0.003). Patients with SO had more severe liver damage: higher grades of moderate/advanced steatosis (64.2% vs. 47.3%), steatohepatitis (44.4% vs. 32.3%) and advanced fibrosis (12.1% vs. 6.0%) (all p≤0.01). One-year post-BS, 58.5% of patients had remission of SO. Patients with persistent SO exhibited less weight-loss than those with SO remission (–23.8 kg vs. –29.1 kg, p<0.001) and had lower rates of remission for T2D (41.9% vs. 69.8%), arterial hypertension (20.8% vs. 45.3%), and metabolic syndrome (47.6% vs. 75.0%) (all p≤0.009). ConclusionThe DXA-based AIM-SO score identifies patients with SO who are at greater risk of hepatic and cardiometabolic comorbidities, and predicts less favorable weight-loss and metabolic improvements post-BS.

Expression of PPAR-γ TF by newly synthesized thiazolidine-2,4-diones to manage glycemic control: Insights from in silico, in vitro and experimental pharmacology in wistar rats.

In pursuit of novel antidiabetic agents to combat type II diabetes mellitus, our study focused on identifying pharmacophoric features responsible for PPAR-γ expression, a key regulator of glucose homeostasis and lipid metabolism. This goal was achieved through pharmacophore model generation and screening of rationally designed library of thiazolidine-2,4-dione hybrids (7a-7f). The top hits were synthesized, characterized, and evaluated for their in vitro and in vivo antidiabetic activities. Among these, compounds 7b and 7c emerged as promising candidates, exhibiting significant in vitro inhibitory activity against human pancreatic α-amylase (HPA) and human liver α-glucosidase (HLAG) enzymes, along with enhanced glucose uptake in L6 myotube cell lines. Specifically, compound 7b showed 29.04±1.13µM HPA inhibition, 34.21±1.16µg/mL HLAG inhibition, and 77.12±1.02% glucose uptake, while compound 7c displayed 28.35±1.01µM HPA inhibition, 26.21±1.17µM HLAG inhibition, and 78.54±0.54% glucose uptake. Mechanistic studies revealed a dose-dependent increase in PPAR-γ transcription factor expression, supported by molecular docking that showed favorable interactions with key residues TYR473, SER289, and HIE323. Molecular dynamics simulations confirmed the stability of these interactions, and MM/GBSA binding free energy calculations indicated potential for further optimization. In vivo studies in STZ-induced diabetic Wistar rats demonstrated significant improvements in glucose homeostasis, insulin sensitivity, and lipid metabolism, with a notable decrease in triglycerides and VLDL levels. Compound 7c also showed an improved pharmacokinetic profile with a half-life of 4.01h and an elimination rate constant of 0.325, compared to compound 7b. Both compounds enhanced glycogen content and antioxidant biomarkers, with a high safety profile (LD50 of 500mg/kg). Overall, compound 7c stands out as a promising lead for further development, with compound 7b also showing strong potential, providing valuable insights for future antidiabetic drug development efforts.

Tissue‐specific methylomic responses to a lifestyle intervention in older adults associate with metabolic and physiological health improvements

AbstractAcross the lifespan, diet and physical activity profiles substantially influence immunometabolic health. DNA methylation, as a tissue‐specific marker sensitive to behavioral change, may mediate these effects through modulation of transcription factor binding and subsequent gene expression. Despite this, few human studies have profiled DNA methylation and gene expression simultaneously in multiple tissues or examined how molecular levels react and interact in response to lifestyle changes. The Growing Old Together (GOTO) study is a 13‐week lifestyle intervention in older adults, which imparted health benefits to participants. Here, we characterize the DNA methylation response to this intervention at over 750 thousand CpGs in muscle, adipose, and blood. Differentially methylated sites are enriched for active chromatin states, located close to relevant transcription factor binding sites, and associated with changing expression of insulin sensitivity genes and health parameters. In addition, measures of biological age are consistently reduced, with decreases in grimAge associated with observed health improvements. Taken together, our results identify responsive molecular markers and demonstrate their potential to measure progression and finetune treatment of age‐related risks and diseases.

Ameliorative effects of Bacillus subtilis C10 on alcoholic liver injury in mice.

Bacillus subtilis has been reported to maintain the homeostasis of intestinal flora. In this study, a mouse model of alcoholic liver injury (ALI) was constructed to study the ameliorative effect of B. subtilis C10 on ALI and to further clarify its mechanism of action. Significant correlations between intestinal flora and biochemical indicators of ALI were found by statistical correlation analysis. Supplementation with B. subtilis C10 modulated the equilibrium of gut flora by reducing the population of detrimental bacteria while enhancing the numbers of beneficial microorganisms, which resulted in an improvement in lipid metabolism and oxidative stress in the liver. The results of RT-qPCR showed that B. subtilis C10 intervention regulated the main regulatory factors of liver lipid metabolism (PPAR-α, SREBP-1c) and interfered with Nrf-2/Ho-1 signal pathway, which in turn ameliorated alcohol-induced lipid metabolism disorder and liver peroxidation stress. In addition, liver metabonomic analysis showed that B. subtilis C10 intervention reduced the production of harmful metabolites and increased beneficial metabolites in the liver, thereby reversing the metabolic disturbances caused by excessive alcohol consumption. KEGG analysis showed that B. subtilis C10 intervention modulated liver metabolic disorders and accelerated lipid metabolism by regulating glutathione metabolic pathway, purine metabolic pathway, pantothenic acid and CoA biosynthesis pathway, ABC transporter protein pathway, and HIF-1 signaling pathway. Taken together, these findings suggest that B. subtilis C10 ameliorates ALI by modifying the structure of intestinal flora and liver metabolic pathways to attenuate alcohol-exposure-induced liver oxidative damage and lipid metabolism abnormalities. PRACTICAL APPLICATION: Bacillus subtilis C10 is an effective probiotic intervention that significantly ameliorated alcoholic liver injury in mice through the gut-liver axis. B. subtilis C10 can be used as a dietary probiotic to develop functional foods with beneficial effects for the population of excessive alcohol consumption.

Metabolomics and proteomics analyses of Chrysanthemi Flos: a mechanism study of changes in proteins and metabolites by processing methods

BackgroundChrysanthemi Flos is a traditional Chinese medicine with a long history of medicinal use. Prior research suggests that the intrinsic composition of Chrysanthemi Flos is affected by shade-drying and oven-drying methods. Nevertheless, the effects of these methods on the proteins and metabolites of Chrysanthemi Flos have not been extensively studied.MethodsThe TMT (tandem mass tag) quantitative proteomics method and the LC–MS/MS (liquid chromatography-tandem mass spectrometry) non-targeted metabolomics method were used to systematically study the differences in the proteins and metabolites during the process of drying Chrysanthemi Flos in the shade and an oven.ResultsDifferentially accumulated metabolites and abundant proteins were primarily enriched in the purine metabolism, pyrimidine metabolism, cyanogenic amino acid metabolism, phenylpropanoid biosynthesis, and starch and sucrose metabolism pathways. Primary metabolites, such as guanine, xanthine, cytidine 5'-diphosphate serine, L-isoleucine, stearidonic acid, alginate, and inulin, play a crucial role in providing energy for Chrysanthemi Flos to withstand desiccation stress. The upregulation of ferulate-5- hydroxylase (F5H), shikimate O hydroxycinnamoyltransferase (HCT), caffeoyl-CoA O-methyltransferase (CCoAOMT), and chalcone isomerase (CHI) enzymes promotes the synthesis of flavonoids, including sinapic acid, caffeoyl shikimic acid, and naringenin chalcone, which possess antioxidant properties. Despite the notable improvements in energy metabolism and antioxidant capacity, these enhancements proved insufficient in halting the senescence and ultimate demise of Chrysanthemi Flos. Moreover, the shade-drying method can inhibit protein expression and promote the accumulation of bioactive components, but the drying efficiency is low, while the oven-drying method exhibits rapid drying efficiency, it does not effectively preserve the components.ConclusionOur study offers a comprehensive explanation for the changes in protein expression and metabolite conversion observed in shade-dried and oven-dried Chrysanthemi Flos, also providing a foundation for optimizing the drying process of Chrysanthemi Flos.

Possible Interaction Between Physical Exercise and Leptin and Ghrelin Changes Following Roux-en-Y Gastric Bypass in Sarcopenic Obesity Patients-A Pilot Study.

Leptin and ghrelin are two hormones that play a role in weight homeostasis. Leptin, which is produced primarily by adipocytes and is dependent on body fat mass, suppresses appetite and increases energy expenditure. Conversely, ghrelin is the "hunger hormone", it stimulates appetite and promotes fat storage. Bariatric surgery significantly alters the levels and activity of these hormones, contributing to weight loss and metabolic improvements. Clarifying the interplay between bariatric surgery, weight loss, physical exercise, leptin, and ghrelin is essential in developing comprehensive strategies for optimizing the long-term outcomes for candidates who have undergone bariatric surgery, especially for sarcopenic patients. This was a randomized controlled study with two groups (n = 22). The patients in both groups had obesity and sarcopenia. A Roux-en-Y-gastric bypass (RYGB) procedure was performed on all patients. The intervention group participated in a structured exercise program three times per week, beginning one month after surgery and lasting 16 weeks. Patient assessment was performed before surgery (baseline) and after the completion of the exercise program. The control group received the usual standard of care and was assessed similarly. After surgery, weight, BMI, and lean mass decreased significantly in both groups between the baseline and the second assessment. Leptin levels were not significantly different between baseline and the second assessment in the physical exercise group, but were significantly lower in the control group (p = 0.05). Ghrelin levels increased over time in both groups, but the differences were not significant. When we associated leptin (the dependent variable) with weight (the independent variable), we found that lower weight was associated with lower leptin levels. A similar relationship was also observed between the leptin and sarcopenia parameters (muscle strength and mass), as well as in the bone health parameters (bone mineral density and t-score). Higher ghrelin levels were significantly associated with higher t-scores and z-scores (p < 0.05). Exercise has been shown to have a significant effect on leptin and ghrelin levels after bariatric surgery. By incorporating regular physical activity into their lifestyle, bariatric patients can optimize their weight loss outcomes and improve their overall health. After the physical exercise protocol, patients in the intervention group revealed more established leptin levels, which may indicate a protected pattern concerning decreased leptin levels. An unfavorable profile was evidenced, according to which greater weight loss, sarcopenia, and osteoporosis were associated with lower leptin levels.

Impact of Gut Microbiome Interventions on Glucose and Lipid Metabolism in Metabolic Diseases: A Systematic Review and Meta-Analysis.

The gut microbiome is increasingly recognized as a key player in metabolic health, influencing glucose and lipid metabolism through various mechanisms. However, the efficacy of gut microbiota-targeted interventions, such as probiotics, prebiotics, fecal microbiota transplantation (FMT), and diet-based treatments, remains unclear for specific metabolic outcomes. In this study, the aim was to evaluate the impact of these interventions on the glucose and lipid parameters in individuals with metabolic diseases such as diabetes mellitus (DM), obesity, and metabolic syndrome. This systematic review and meta-analysis included 41 randomized controlled trials that investigated the effects of gut microbiota-targeted treatments on metabolic parameters such as fasting glucose, glycated hemoglobin (HbA1c), homeostatic model assessment for insulin resistance (HOMA-IR), total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides. A comprehensive search was conducted using databases like PubMed, Google Scholar, and Scopus, focusing on interventions targeting the gut microbiota. A meta-analysis was performed using random-effects models, with effect sizes calculated for each outcome. Risk of bias was assessed using the Cochrane Risk of Bias tool. Gut microbiota-targeted interventions significantly reduced fasting glucose, HbA1c, HOMA-IR, total cholesterol, LDL-C, and triglycerides, with moderate heterogeneity observed across studies. The interventions also led to modest increases in HDL-C levels. Probiotic and synbiotic interventions showed the most consistent benefits in improving both glucose and lipid profiles, while FMT yielded mixed results. Short-term interventions showed rapid microbial shifts but less pronounced metabolic improvements, whereas longer-term interventions had more substantial metabolic benefits. In this study, it is demonstrated that gut microbiota-targeted interventions can improve key metabolic outcomes, offering a potential therapeutic strategy for managing metabolic diseases. However, the effectiveness of these interventions varies depending on the type, duration, and population characteristics, highlighting the need for further long-term studies to assess the sustained effects of microbiota modulation on metabolic health.

BS O02 - Impact of Bariatric surgery on Obesity Indices and Reproductive Hormones: A Prospective Study in Morbidly Obese Women

Abstract Background Obesity, defined by a BMI of 30 kg/m² or higher, is influenced by genetics, socio-economic, and cultural factors. Genetic predispositions affect metabolism and energy regulation, while environmental factors like sedentary lifestyles and poor food environments worsen obesity. Obesity disrupts hormonal balances, impacting sex hormone levels and menstrual cycles, leading to infertility in women. This hormonal imbalance affects oocyte quality and ovulation. Bariatric surgery offers significant weight loss and metabolic improvements, enhancing reproductive hormone profiles and insulin sensitivity. Our study explores how sleeve gastrectomy affects BMI and hormone levels, aiming to understand its impact on obesity management and reproductive health. Method This prospective observational study examines the effects of laparoscopic sleeve gastrectomy on reproductive hormones and ovarian function in 32 morbidly obese women, adhering to Helsinki Declaration ethics. Participants, aged 18-50 with no menopause or chronic illness, consented to the study. Exclusions included those with polycystic ovary syndrome, recent reproductive organ surgery, or recent infertility medications. The study assessed changes in BMI, antral follicles, anti-Müllerian hormone, and reproductive hormones before surgery and at 6 and 12 months post-surgery. Blood samples and transvaginal ultrasounds were conducted preoperatively and at 6 and 12 months postoperatively to monitor outcomes. Results The study involved participants with an average age of 33 and a mean BMI of 42.12. Significant changes were observed post-sleeve gastrectomy at 6 and 12 months (p &amp;lt; 0.001). At 6 months, BMI decreased by 9.24 units, AMH levels dropped from 3 to 2.5 ng/mL, and antral follicle counts in both ovaries declined. By 12 months, BMI decreased by 16.47 units, AMH levels fell to 2 ng/mL, and antral follicle counts further reduced. Hormonal changes included increases in FSH, LH, and estradiol, while SHBG levels rose, and free testosterone levels decreased significantly. Conclusion Individual hormone responses to weight loss and surgery necessitate personalized obesity treatments. Tailoring surgical approaches and care to hormonal profiles can optimize outcomes and reduce complications. Monitoring AMH levels post-surgery can offer insights into reproductive effects, aiding clinical management and counseling for women with obesity-related infertility. We highlight the significant impact of sleeve gastrectomy on physiological parameters in obese individuals, especially regarding reproductive health and metabolic regulation. The findings enhance understanding of the changes associated with bariatric surgery and its potential benefits for metabolic and reproductive health.

Improvements in Insulin Resistance and Glucose Metabolism Related to Breastfeeding Are Not Mediated by Subclinical Inflammation.

Background: Lactation is known to improve insulin resistance, but this phenomenon remains poorly understood. Our goal was to evaluate whether subclinical inflammation could mediate the association between breastfeeding (BF) and improvement in glucose metabolism and markers of insulin resistance (MIRs) in the postpartum. Methods: A total of 95 adult women (≥18 years) with a BMI ≥ 25 kg/m2 from the outpatient clinic of the Federal University of São Paulo were followed from early pregnancy until 60 to 180 days postpartum. The patients were divided based on their BF status: BF and non-BF groups. A latent variable termed SubInf was created incorporating inflammation-related biomarkers: adiponectin, E-selectin, branched-chain amino acids, zonulin, copeptin, and lipopolysaccharides. The association of BR with MIRs in the postpartum was evaluated through linear regression analysis, and mediation analysis was performed to evaluate the role of SubInf in this association. Results: The groups were similar regarding gestational diabetes mellitus (GDM) prevalence, pre-gestational BMI, caloric intake, physical activity, and postpartum weight loss. The BF group presented lower levels of triglycerides (TGs), fasting glucose, fasting insulin, TG/HDLcholesterol ratio (TG/HDL), TyG index, and HOMA-IR compared to the non-BF group. A linear regression analysis adjusted for scholarity, parity, pre-gestational BMI, GDM, weight gain during pregnancy, and mode of delivery revealed an inverse association between BF and fasting glucose [-6.30 (-10.71 to -1.89), p = 0.005), HOMA-IR [-0.28 (-0.50 to -0.05), p = 0.017], TyG index [-0.04 (-0.06 to -0.01), p = 0.002], and TG/HDL ratio [-0.23 (-0.46 to -0.01), p = 0.001]. In the mediation analysis, SubInf did not mediate the indirect effect of BF on MIRs. Conclusions: In overweight and obese women, an association between BF and improvement in MIRs in the postpartum was seen, corroborating that BF should be stimulated, especially in these cardiometabolic high-risk women. Subclinical inflammation did not seem to mediate this association.

Multi-Omics Reveal the Improvements of Nutrient Digestion, Absorption, and Metabolism and Intestinal Function via GABA Supplementation in Weanling Piglets.

The nonprotein amino acid γ-aminobutyric acid (GABA) can enhance intestinal function in piglets; however, the mechanisms involved are not yet fully understood. To explore the effects of GABA and its underlying mechanisms, weanling piglets were randomly assigned to three groups, receiving either a basal diet or a basal diet supplemented with GABA (80 mg/kg or 120 mg/kg). The results demonstrated that dietary GABA improved growth performance and reduced diarrhea incidence (p < 0.05). Additionally, GABA supplementation decreased the serum and intestinal levels of pro-inflammatory cytokines (p < 0.05), and improved intestinal morphology. Multi-omics analyses were employed to explore the alterations caused by GABA supplementation and elucidate the related mechanisms. Microbiota profiling revealed improved beta-diversity and changes in the composition of ileal bacteria and fungi. Amino acid metabolism, lipid metabolism, and digestive processes were primarily enriched in the GABA group according to metabolomics analysis. A transcriptome analysis showed significant enrichment in ion transmembrane transport and nutrition absorption and digestion pathways in the ileum. Furthermore, increased lipase and trypsin activity, along with the elevated expression of tight junction proteins confirmed the beneficial effects of GABA on intestinal nutrient metabolism and barrier function. In conclusion, dietary 80 mg/kg GABA supplementation improved nutrient digestion and absorption and intestinal function in weanling piglets.

Beyond soybean meal: investigating the effects of dietary protein alternatives on gut health, liver function and microbiota in traditional slow-growing chicken breeds

The use of soybean meal in animal feed is crucial for nutrition but has a significant environmental impact, especially related to deforestation and biodiversity loss. With the increasing demand for sustainable agricultural practices, it becomes essential to explore alternatives to soybean meal. This study evaluated the effect of a soy-free diet, replaced with fava beans and pea protein, on an Italian slow-growing chicken breed: the Bianca di Saluzzo. The results indicate that the experimental diet did not compromise the growth, final weight or intestinal health of the animals, demonstrating a good tolerance and adaptability of the breed to these alternative ingredients. Furthermore, the analysis of the intestinal microbiota showed a positive impact, with an increase in organic acids such as succinic and citric, which could improve intestinal health and metabolic efficiency. Some changes in liver enzyme levels were observed, such as the increase in glutamate-oxaloacetate transaminase, an enzyme involved in amino acid metabolism. This increase could indicate a higher efficiency in protein metabolism, suggesting that the diet based on alternative ingredients could support an improvement in liver metabolism. Although this aspect deserves further investigation, it could represent a positive effect of the diet on liver function and overall health of the animals. Further studies are needed to fully understand the long-term implications of these dietary modifications, particularly in relation to the gut microbiota and metabolism.

Organophosphorus Flame Retardants and Metabolic Disruption: An in Silico, in Vitro, and in Vivo Study Focusing on Adiponectin Receptors.

Environmental chemical exposures have been associated with metabolic outcomes, and typically, their binding to nuclear hormone receptors is considered the molecular initiating event (MIE) for a number of outcomes. However, more studies are needed to understand the influence of such exposures on cell membrane-bound adiponectin receptors (AdipoRs), which are critical metabolic regulators. We aimed to clarify the potential interactions between AdipoRs and environmental chemicals, specifically organophosphorus flame retardants (OPFRs), and the resultant effects. Employing in silico simulation, cell thermal shift, and noncompetitive binding assays, we screened eight OPFRs for interactions with AdipoR1 and AdipoR2. We tested two key events underlying AdipoR modulation upon OPFR exposure in a liver cell model. The Toxicological Prioritization Index (ToxPi)scoring scheme was used to rank OPFRs according to their potential to disrupt AdipoR-associated metabolism. We further examined the inhibitory effect of OPFRs on AdipoR signaling activation in mouse models. Analyses identified pi-pi stacking and pi-sulfur interactions between the aryl-OPFRs 2-ethylhexyl diphenyl phosphate (EHDPP), triphenyl phosphate (TPhP), and tricresyl phosphate (TCP) and the transmembrane cavities of AdipoR1 and AdipoR2. Cell thermal shift assays showed a rightward shift in the AdipoR proteins' melting curves upon exposure to these three compounds. Although the binding sites differed from adiponectin, results suggest that aryl-OPFRs noncompetitively inhibited the binding of the endogenous peptide ligand ADP355 to the receptors. Analyses of key events underlying AdipoR modulation revealed that glucose uptake was notably lower, whereas lipid content was higher in cells exposed to aryl-OPFRs. EHDPP, TCP, and TPhP were ranked as the top three disruptors according to the ToxPi scores. A noncompetitive binding between these aryl-OPFRs and AdipoRs was also observed in wild-type (WT) mice. In db/db mice, the finding of lower blood glucose levels after ADP355 injection was diminished in the presence of a typical aryl-OPFR (TCP). WT mice exposed to TCP demonstrated lower AdipoR1 signaling, which was marked by lower phosphorylated AMP-activated protein kinase (pAMPK) and a higher expression of gluconeogenesis-related genes. Moreover, WT mice exposed to ADP355 demonstrated higher levels of pAMPK protein and peroxisome proliferator-activated receptor- messenger RNA. This was accompanied by higher glucose disposal and by lower levels of long-chain fatty acids and hepatic triglycerides; these metabolic improvements were negated upon TCP co-treatment. In silico, in vitro, and invivo assays suggest that aryl-OPFRs act as noncompetitive inhibitors of AdipoRs, preventing their activation by adiponectin, and thus function as antagonists to these receptors. Our study describes a novel MIE for chemical-induced metabolic disturbances and highlights a new pathway for environmental impact on metabolic health. https://doi.org/10.1289/EHP14634.

Efficacy of single anastomosis sleeve-ileal bypass in weight control and resolution of type 2 diabetes mellitus – a retrospective cohort study

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder exacerbated by obesity. Single Anastomosis Sleeve-Ileal Bypass (SASI) has emerged as a promising metabolic bariatric procedure that combines sleeve gastrectomy and ileal bypass, facilitating substantial weight loss and T2DM remission through restrictive and malabsorptive mechanisms. This study aims to evaluate the effects of SASI on T2DM remission, weight loss, and safety in one year follow-up. A retrospective cohort study analyzed 31 patients with obesity and T2DM who underwent SASI. Data collected included demographic characteristics, preoperative and postoperative BMI, HbA1c levels, and bariatric outcomes, including %TWL and T2DM changes. The mean age was 45 years, with a mean preoperative BMI of 40.7 kg/m². One year postoperatively, the mean %EWL was 85.6% and %TWL was 31.7%. T2DM remission was achieved in 24 (77.4%) patients, improvement in 4 (12.9%), and no change in 3 (9.7%). Hypertension improved in 21 (87.5%) patients, with 12 (50%) achieving remission. Significant reductions in BMI and HbA1c levels were observed (p < 0.001). Responders (R) and non-responders (NR) groups showed significant differences in postoperative BMI and %EWL (p = 0.007, p = 0.023). One patient experienced a Clavien-Dindo Grade III complication; no deaths occurred. SASI is an effective and safe procedure for treating T2DM, resulting in significant weight loss and metabolic improvements over a one-year follow-up. SASI seems to be a favorable option for T2DM management in metabolic bariatric surgery.

Improvement in Symptoms of Depression and Anxiety and Cardiometabolic Risk Factors in Children and Adolescents with Overweight and Obesity Following the Implementation of a Multidisciplinary Personalized Lifestyle Intervention Program.

Background/Objectives: Childhood obesity is one of the most challenging contemporary public health problems. Children and adolescents with obesity experience multiple psychosocial difficulties, such as low self-esteem, depression, anxiety, and behavioral problems, which persist for a long time. The aim of the study was to assess the effect of a multidisciplinary personalized lifestyle intervention for depressive and anxiety symptoms, as evaluated by psychometric questionnaires, and their effect and association with cardiometabolic parameters in children and adolescents with overweight and obesity before and after the intervention. Methods: Six hundred and eleven (n = 611) children and adolescents (mean age ± SE: 10.39 ± 0.10 years; 51.5% females, 46.6% pubertal) were studied prospectively. Subjects were classified as being obese (50.2%), overweight (33.5%), or having a normal BMI (16.2%) according to IOTF criteria. All participants entered a 1-year lifestyle intervention program; laboratory investigations were obtained at the beginning and end of the study and two psychometric questionnaires were completed, the CDI and SCARED, which evaluate symptoms of depression and anxiety, respectively. Results: Following the lifestyle intervention, a significant decrease was noted in anxiety scores in all subjects and in depression scores in youth with obesity, as well as in adolescents with obesity, while females displayed a reduced response to the intervention. Insulin resistance and metabolic syndrome parameters, cortisol, PRL, and LH concentrations were positive predictors for depressive and anxiety symptoms. Conclusions: The implementation of a multidisciplinary personalized lifestyle intervention program in the management of childhood obesity is associated with a significant decrease in cardiometabolic and psychosocial comorbidities in children with and without excess adiposity. The improvement in mental health is likely mediated by an improvement in energy metabolism with subsequent improvement in neuroinflammation owing to lifestyle changes.

Morus alba: natural and valuable effects in weight loss management.

Overweight and obesity are conditions associated with serious comorbidities, such as diabetes and cardiovascular disease. Prevalence of excessive fat accumulation is increasing worldwide, and thus the need for efficient and sustainable weight loss regimes has become a major issue in clinical practice. Despite the important advances in the development of anti-obesity medications (AOM), their side effects, cost, and accessibility, are limiting factors for their routine use. Conversely, the studies of medicinal plants for weight management holds strong promise as a growing area of research. This review consolidates the representative evidence about the beneficial impacts of Morus alba on weight management and associated metabolic parameters, encompassing: inhibition of digestive enzymes, and thus contribution to the energy deficit required for weight loss, improvements in glucose and lipid metabolism, and attenuation of adiposity. Findings from in vitro, in vivo, and clinical investigations reviewed in the paper, demonstrate that white mulberry extracts have the potency to supplement efficiently and safely a healthy weight management approach.