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Maternal exercise is beneficial for offspring brain development. Amyloid precursor protein (APP) influences neurogenesis and synaptic plasticity. Cleavage products of APP are implicated in the proliferation of neural progenitor cells and neuronal network development. Our study aimed to investigate differences in APP processing in active or sedentary offspring of dams who were exposed to voluntary wheel running with and without a western diet throughout gestation. Female Wistar rats (7–8 weeks old) were fed a normal chow or western diet and randomized into voluntary wheel run or sedentary conditions. Dams returned to sedentary conditions post-parturition. The pups were weaned at 6 weeks after which point half of the samples were collected, while the rest of the pups remained on a normal diet, separated into sedentary or voluntary wheel run groups, and collected 12 weeks later. In utero exposure to maternal exercise was associated with higher neuronal nuclear protein, higher soluble APPα and lower soluble APPβ in offspring prefrontal cortex tissue at 6, but not 18 weeks of age. Neuronal nuclear protein is exclusive to mature neurons implying that offspring of mothers who exercised could have more neuron maturation potentially influenced by the higher APPα content at this early developmental stage. The voluntary wheel run offspring groups had a higher mature/pro brain derived neurotrophic factor ratio compared to the sedentary counterparts. The maternal effects were isolated to the juvenile 6-week-old pups, while the differences in the adult offspring were caused by their own exercise status. [ABSTRACT FROM AUTHOR]

Alzheimer's disease is the most common form of dementia and is a challenge for the modern world due to the due to aging populations. Researchers are trying their best to understand the mechanisms of onset and find effective ways to treat and prevent this disease. The purpose of the following paper is to present the impact of physical activity in the development of Alzheimer's disease. Numerous studies confirm that regular workouts have a positive reflection in the form of slowing the aging of the brain and alleviation of neuropsychiatric symptoms in affected individuals. During muscle work irisin is produced, which plays an important role in the formation of neurons and exhibits an anti-inflammatory effects. This review also looks at the aspect of maintaining proper composition of the gut microbiota, whose imbalance can promote the process of neuronal inflammation and cognitive dysfunction. Attention is also given to issues of training intensity and the effect of of exercise on blood flow in the brain. All of these elements play an important role in preventing and slowing down neurodegeneration. Purpose : The purpose of this scientific paper is to review the current knowledge of the effects of physical activity on the development of Alzheimer's disease. Review methods : We conducted our study as a literature review based on information gathered from PubMed, Embase, Google Scholar using combinations of the following keywords : Alzheimer's disease ; dementia ; physical activity ; cerebral blood flow ; gut-brain axis ; irisin. The state of knowledge : Alzheimer's disease is the most common type of dementia and one of the main neurodegenerative disorders affecting elderly people. Numerous studies confirm that regular exercise has a positive effect on slowing down brain aging and alleviating neuropsychiatric symptoms in patients. According to current knowledge, nerve cell degeneration can be exacerbated by peripheral inflammation that occurs in obesity. An imbalance of bacterial flora in the gastrointestinal tract causes systemic inflammation in the body. This in turn leads to excessive production of pro-inflammatory cytokines and activation of microglia so that the blood-brain barrier becomes leaky. Maintaining the appropriate composition of the gut microbiota plays an important role, as its imbalance can promote neuronal inflammation and cognitive impairment. During physical activity, irisin protein is produced in muscle tissue, which plays an important role in neuronal formation and exhibits anti-inflammatory effects. Currently, there is evidence that irisin can provide a number of beneficial effects, mainly through mechanisms that positively affect the gut microbiome. Attention is also given to issues of training intensity and the effect of exercise on cerebral blood flow. All these factors play an important role in preventing and slowing down neurodegeneration. Conclusion : Based on a review of the available literature, a significant effect of physical activity on the development of Alzheimer's disease can be demonstrated. The accumulated data suggest that physical activity is one of the main protective factors against the development and progression of Alzheimer's disease. Physical activity is associated with a reduction in cardiovascular risk factors and an increase in neuroprotective changes. The neuroprotective effect of physical exercise is dependent on its intensity. In addition, the role of the gut microbiota has been shown to be important for maintaining normal cognitive function. The protein irisin may also have significant neuroprotective potential in relation to the development and progression of cognitive disorders. Physical activity may be one of the strategies to prevent an increase in the incidence of Alzheimer's disease with positive health, economic and social implications in the future. [ABSTRACT FROM AUTHOR]

Heart failure (HF), which has a high morbidity and mortality rate, is nevertheless a common and crippling ailment, especially in older populations. The complicated pathophysiology of heart failure (HF), which includes oxidative stress, endothelial dysfunction, fibrosis, and inflammation, is frequently not sufficiently treated despite advances in medication. Inhibitors of the sodium-glucose co-transporter 2 (SGLT2) have become a key treatment for HF in patients with varying left ventricular ejection fractions (LVEF). SGLT2 inhibitors have been shown in recent clinical trials to considerably lower hospitalization rates for heart failure, cardiovascular mortality, and all-cause mortality. The mechanisms of SGLT2 inhibitors, such as better ventricular loading, increased heart metabolic efficiency, and decreased inflammation and necrosis, are covered in this review. Additionally, we provide an overview of four important clinical trials--DAPA-HF, EMPEROR-Reduced, EMPEROR-Preserved, and DELIVER--highlighting their effectiveness in lowering unfavorable cardiovascular outcomes for patients with heart failure who have preserved (HFpEF), slightly reduced (HFmrEF), or reduced (HFrEF). The results validate the need of SGLT2 inhibitors in allinclusive HF treatment plans by highlighting their adaptability and safety in a range of clinical contexts. [ABSTRACT FROM AUTHOR]

Introduction: Metabolic dysfunction-associated fatty liver disease (MAFLD) has emerged as the leading cause of hepatocellular carcinoma (HCC) worldwide. Over the years, Perilipin 5 (PLIN5) has been recognized as a key regulator of both MAFLD and HCC development. In our previous studies we demonstrated that deficiency in Plin5 reduces the severity of MAFLD and HCC in mice. Interestingly, it has been established that patients with MAFLD and HCC exhibit various changes in their gut microbiome profiles. The gut microbiome itself has been shown to play a role in modulating carcinogenesis and the immune response against cancer. Methods: Therefore, we conducted a study to investigate the alterations in fecal microbiome composition in wild type (WT) and Plin5-deficient (Plin5-/-) mice models of MAFLD and MAFLD-induced HCC (MAFLD-HCC). We utilized 16S rRNA gene sequencing analysis to profile the composition of gut bacteria in fecal samples. Results: Notably, we discovered that the absence of Plin5 alone is already associated with changes in gut microbiota composition. Moreover, feeding the mice a Western diet (WD) resulted in additional microbial alterations. Interestingly, Plin5-/- animals exhibited an enrichment of the beneficial taxa Lactobacillus in both animal models. Discussion: Our findings identify Plin5 as a major regulator of gut microbiota during the development of MAFLD and MAFLD-HCC. [ABSTRACT FROM AUTHOR]

Background Objective Materials and methods Results Conclusions Dietary patterns may affect sperm quality, but the scientific evidence is limited.To evaluate the association between adherence to different a‐priori dietary patterns and sperm quality parameters in healthy reproductive‐age men.A cross‐sectional analysis was conducted using data from 200 young men enrolled in the Led‐Fertyl study. Tertiles of six a‐priori dietary patterns were estimated: four healthy dietary patterns [Mediterranean Diet Adherence Screener (MEDAS), Dietary Approaches to Stop Hypertension (DASH), Healthful Plant‐Based Diet Index (hPDI) and EAT‐Lancet Score], and two unhealthy dietary patterns [Western Diet and Unhealthful Plant‐Based Diet Index (uPDI)]. Sperm quality parameters (count, concentration, vitality, total and progressive motility, and normal morphology) were considered the main outcomes.Compared with the lowest tertile, participants in the highest MEDAS tertile had higher total sperm count (β = 3.2;95%CI: 1.0, 5.5) and concentration (β = 1.8;95%CI: 0.6, 3.0), and total (β = 8.2;95%CI: 1.3, 15.1) and progressive motility (β = 7.1;95%CI: 0.2, 14.0). Similarly, participants in the highest hPDI tertile had higher total sperm count (β = 3.4;95%CI: 1.4, 5.5) and concentration (β = 1.2;95%CI: 0.0, 2.3) compared with those in the lowest tertile. When these dietary patterns were modelled as continuous variables (for each 1‐point increment in the specific score), an inverse association was found between the uPDI and Western and total sperm count [(β = ‐2.7;95%CI: ‐4.8, ‐0.7) and (β = ‐3.8;95%CI: ‐5.8, ‐1.7), respectively] and sperm concentration [(β = ‐1.2;95%CI: ‐2.4, ‐0.1) and (β = ‐1.7;95%CI: ‐2.8, ‐0.5), respectively]. Compared with participants in the lowest tertile, those in the highest uPDI tertile presented higher odds of abnormal sperm concentration (OR: 4.6;95%CI: 1.0, 19.9) and one or more seminogram abnormalities (OR: 2.3;95%CI: 1.1, 5.0).Our findings suggest that higher adherence to healthy dietary patterns (Mediterranean and healthful plant‐based diet) was positively associated with better sperm quality parameters, in contrast, greater adherence to unhealthy dietary patterns was inversely associated. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion Increasing the dietary intake of K+ in the setting of a high salt intake promotes renal Na+ excretion even though K+ concurrently enhances the secretion of aldosterone, the most effective stimulus for renal Na+ reabsorption. Here, we questioned whether in the high salt state a mechanism exists, which attenuates the aldosterone response to prevent renal Na+ reabsorption after high K+ intake.Mice were fed diets containing varying amounts of Na+ combined with KCl or KCitrate. Murine cortical connecting duct (mCCDcl1) cells were cultured in media containing normal or high [Cl−]. The response to aldosterone was analyzed by high‐resolution imaging and by biochemical approaches.The canonical cellular response to aldosterone, encompassing translocation of the mineralocorticoid receptor (MR) and activation of the epithelial Na+ channel ENaC was repressed in Na+‐replete mice fed a high KCl diet, even though plasma aldosterone concentrations were increased. The response to aldosterone was restored in Na+‐replete mice when the extracellular [Cl−] increase was prevented by feeding a high KCitrate diet. In mCCDcl1 cells, an elevated extracellular [Cl−] was sufficient to disrupt the aldosterone‐induced MR translocation.These findings indicate a pivotal role for extracellular [Cl−] in modulating renal aldosterone signaling to adapt MR activation by a high K+ intake to the NaCl balance. An impairment of [Cl−]‐mediated aldosterone resistance may contribute to excessive MR activation by aldosterone in the presence of a high salt intake characteristic of the Western diet, resulting in an inappropriate salt reabsorption and its downstream detrimental effects. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction-associated Steatohepatitis (MASH), is a prominent cause for liver cirrhosis. MASH-cirrhosis is responsible for liver complications and there is no specific treatment. To develop new therapeutic approaches, animal models are needed. The aim of this study was to develop a fast animal model of MASH-cirrhosis in rats reflecting the human disease. Carbon tetrachloride (CCl4) injections in combination with a high-fat Western diet (WD) were used to induce MASH-cirrhosis. To accelerate liver injury, animals received phenobarbital (PB) in their drinking water using two different regimens. Rats developed advanced MASH-cirrhosis characterized by portal hypertension, blood biochemistry, hepatic ballooning, steatosis, inflammation and fibrosis. Importantly, rats receiving low-dose PB for the long term (LT) showed ascites after 6 weeks, whereas rats with high-dose short-term (ST) PB developed ascites after 8 weeks. ST- and LT-treated rats showed increased portal pressure (PP) and decreased mean arterial pressure (MAP). Of note, hepatocyte ballooning was only observed in the LT group. The LT administration of low-dose PB with CCl4 intoxication and WD represents a fast and reproducible rat model mimicking decompensated MASH-cirrhosis in humans. Thus, CCl4 + WD with LT low-dose phenobarbital treatment might be the preferred rat animal model for drug development in MASH-cirrhosis. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) arising from metabolic dysfunction-associated steatohepatitis (MASH) presents a significant clinical challenge, particularly given the prevalence of the Western diet (WD). The influence of diet on the tumor microenvironment remains poorly understood. Galectin-1 (Gal-1) is a biomarker for HCC and has a crucial role in liver carcinogenesis. Our previous studies demonstrated that silencing Gal-1 effectively treats mouse HCC. However, the impacts of a WD on Gal-1 signaling on MASH to HCC progression are unknown, and this study addresses these knowledge gaps. Methods: We developed a novel MASH-HCC mouse model. Using spatial transcriptomics and multiplex immunohistochemistry (IHC), we studied the effects of a WD on the liver and tumor microenvironment. By modulating Gal-1 expression through silencing and overexpression, we explored the location-specific impacts of WD on Gal-1 signaling. Results: Pathways such as Rho signaling, extracellular matrix (ECM) remodeling, and senescence-associated secretory phenotypes (SASP) were prominently activated in WD-induced metabolic dysfunction-associated fatty liver disease (MAFLD) and MASH-HCC, compared to healthy livers controls. Furthermore, Rho GTPase effectors, ECM remodeling, neutrophil degranulation, cellular stress, and cell cycle pathways were consistently enriched in human and mouse MASH-HCC. Spatially, these pathways were enriched in the tumor and tumor margins of mouse MASH-HCC. Additionally, there was a notable increase in CD11c and PD-L1-positive cells from non-tumor tissues to the tumor margin and inside the tumor of MASH-HCC, suggesting compromised immune surveillance due to WD intake. Moreover, MASH-HCC exhibited significant Gal-1 induction in N-Cadherin-positive cells, indicating enhanced epithelial-to-mesenchymal transition (EMT). Modulating Gal-1 expression in MASH-HCC further established its specific roles in regulating Rho signaling and SASP in the tumor margin and non-tumor tissues in MASH-HCC. Conclusion: WD intake significantly influences vital cellular processes involved in Gal-1-mediated signaling, including Rho signaling and ECM remodeling, in the tumor microenvironment, thereby contributing to the development of MASH-HCC. [ABSTRACT FROM AUTHOR]

Introduction: The global obesity crisis results from inactive lifestyles and poor diets, increasing the risk of metabolic disorders. Emerging research links obesity with gut microbiome changes influenced by factors like age, genetics, and diet. Gut-brain communication via neural, endocrine, and inflammatory pathways, influenced by microbial compounds, affects nervous system function. Materials and Methods of Research: A thorough literature review was performed using PubMed and Google Scholar, employing keywords related to the gut-brain axis and obesity. Results: Obesity shifts gut microbiota composition due to factors like childbirth method, diet, antibiotics, and environment. This imbalance impacts metabolism, appetite, and insulin sensitivity. Gut microbes influence the brain, regulating energy balance and inflammation. Dysregulated tryptophan metabolism leads to insulin resistance. Gut-brain communication via the vagal nerve affects nutrient metabolism. Hormones like insulin and leptin, along with microbial metabolites, affect lipid metabolism and appetite. Gut microbiota abundance correlates with leptin signaling, and changes in ghrelin levels relate to microbiota composition. Microbial presence affects food cravings. Inflammation in obesity is linked to gut microbiota changes, mediated by bile acids and microbial metabolites. Interventions like probiotics and fecal microbiota transplantation offer potential for managing obesity. Emerging therapies like peptide D3 hold promise but require further study. Conclusion: The microbiome-gut-brain axis is vital in obesity, affecting metabolism, inflammation, and appetite. Utilizing interventions such as dietary adjustments and probiotics targeting gut-brain signaling shows promise in managing obesity. Personalized approaches are crucial due to microbiome complexity. Further research is needed to develop effective therapies for the obesity epidemic. [ABSTRACT FROM AUTHOR]

Background: The gut microbiome is thought to play an important role in the development of colorectal cancer (CRC). However, as the gut microbiome varies widely based on diet, we sought to investigate the gut microbiome changes in patients with CRC in a South Asian population. Methods: The gut microbiome was assessed by 16s metagenomic sequencing targeting the V4 hypervariable region of the bacterial 16S rRNA in stool samples (n = 112) and colonic tissue (n = 36) in 112 individuals. The cohort comprised of individuals with CRC (n = 24), premalignant lesions (n = 10), healthy individuals (n = 50) and in those with diabetes (n = 28). Results: Overall, the relative abundances of genus Fusobacterium (p < 0.001), Acinetobacter (p < 0.001), Escherichia-Shigella (p < 0.05) were significantly higher in gut tissue, while Romboutsia (p < 0.01) and Prevotella (p < 0.05) were significantly higher in stool samples. Bacteroides and Fusobacterium were the most abundant genera found in stool samples in patients with CRC. Patients with pre-malignant lesions had significantly high abundances of Christensenellaceae, Enterobacteriaceae, Mollicutes and Ruminococcaceae (p < 0.001) compared to patients with CRC, and healthy individuals. Romboutsia was significantly more abundant (p < 0.01) in stool samples in healthy individuals compared to those with CRC and diabetes. Conclusion: Despite marked differences in the Sri Lankan diet compared to the typical Western diet, Bacteroides and Fusobacterium species were the most abundant in those with CRC, with Prevotella species, being most abundant in many individuals. We believe these results pave the way for possible dietary interventions for prevention of CRC in the South Asian population. [ABSTRACT FROM AUTHOR]

Background: This study focused on type 2 diabetes mellitus (T2DM) in a group of adult Mixe, an Indigenous population from Oaxaca, Mexico. Mixe comprised an estimated 9.4% (n ≅ 90 000) of the Indigenous population in Oaxaca. Mexico. Objective: This study focused on a group of adult Mixe, an Indigenous population from Oaxaca, Mexico. To compare the prevalence of T2DM, overweight (OW), obesity (OB), and hypertension (HTN) between 2007 and 2017 for a small, isolated Mixe community in the Valley of Oaxaca, Mexico. We test whether or not environmental changes have affected T2DM prevalence. Methods and Materials: Demographic and medical record data were collected in the community in 2007 and 2017 from the medical clinic and the mayor's office. T2DM was medically diagnosed among adults (>34 years old), in 2007 (n = 730) and in 2017 (n = 829). Results: T2DM crude prevalence increased from 6.7% to 12.1% (p <.001) from 2007 to 2017. The mean age of the sample analyzed was 60.6 (SD = 9.7). Age‐adjusted T2DM prevalence increased from 6.7% to 10.8% (p <.002). T2DM was 5.7%–5.5% among males (p <.53) and 7.1%–13.6% among females (p <.001). Sex‐specific OW and OB simulation studies indicate females had 7% less OW in 2007, and males were unchanged compared with 2017. OB among males and females was significantly higher in 2017 compared with 2007 (increased by 15.2% and 8.3%, males and females, respectively). Sexes combined OW + OB increased 12.7% among males but was unchanged in females (−0.5%). In the sexes combined analysis, OW prevalence increased 12.7% to 27.1% (p <.001) and OB prevalence increased 10.7%–27.9% (p <.001) from 2007 to 2017. HTN did not change significantly from 2007 to 2017 (15.4% and 14.6%, respectively) (p =.63) in adults. Among T2DM individuals, the frequency of HTN was not significantly different in 2007 and 2017 (57.1% and 37%, respectively) (p =.65). Transition to a Western diet consisting of high‐carbohydrate foods occurred at the same time as increased T2DM from 2007 to 2017, with a higher prevalence of T2DM noted among females in 2017. Conclusions: An increased prevalence of T2DM, OW, and OB but not HTN was observed in the Mixe community from 2007 to 2017 and was associated with the adoption of a high‐carbohydrate Western diet. [ABSTRACT FROM AUTHOR]

Eukaryotic elongation factor 1A1 (EEF1A1), originally identified for its role in protein synthesis, has additional functions in diverse cellular processes. Of note, we previously discovered a role for EEF1A1 in hepatocyte lipotoxicity. We also demonstrated that a 2-wk intervention with the EEF1A1 inhibitor didemnin B (DB) (50 µg/kg) decreased liver steatosis in a mouse model of obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) [129S6/SvEvTac mice fed Western diet (42% fat) for 26 wk]. Here, we further characterized the hepatic changes occurring in these mice by assessing lipid droplet (LD) size, bulk differential expression, and cell type-associated alterations in gene expression. Consistent with the previously demonstrated decrease in hepatic steatosis, we observed decreased median LD size in response to DB. Bulk RNA sequencing (RNA-Seq) followed by gene set enrichment analysis revealed alterations in pathways related to energy metabolism and proteostasis in DB-treated mouse livers. Deconvolution of bulk data identified decreased cell type association scores for cholangiocytes, mononuclear phagocytes, and mesenchymal cells in response to DB. Overrepresentation analyses of bulk data using cell type marker gene sets further identified hepatocytes and cholangiocytes as the primary contributors to bulk differential expression in response to DB. Thus, we show that chemical inhibition of EEF1A1 decreases hepatic LD size and decreases gene expression signatures associated with several liver cell types implicated in MASLD progression. Furthermore, changes in hepatic gene expression were primarily attributable to hepatocytes and cholangiocytes. This work demonstrates that EEF1A1 inhibition may be a viable strategy to target aspects of liver biology implicated in MASLD progression. NEW & NOTEWORTHY: Chemical inhibition of EEF1A1 decreases hepatic lipid droplet size and decreases gene expression signatures associated with liver cell types that contribute to MASLD progression. Furthermore, changes in hepatic gene expression are primarily attributable to hepatocytes and cholangiocytes. This work highlights the therapeutic potential of targeting EEF1A1 in the setting of MASLD, and the utility of RNA-Seq deconvolution to reveal valuable information about tissue cell type composition and cell type-associated gene expression from bulk RNA-Seq data. [ABSTRACT FROM AUTHOR]

Background: Metabolic dysfunction‐associated steatotic liver disease (MASLD) affects approximately 20%–30% of the general population and is linked to high‐caloric western style diet. However, there are little data that specific nutrients might help to prevent steatosis. Methods: We analysed the UK Biobank (ID 71300) 24 h‐nutritional assessments and investigated the association between nutrient intake calculated from food questionnaires and hepatic steatosis indicated by imaging or ICD10‐coding. The effect of manganese (Mn) on subgroups with risk single nucleotide polymorphism carriage as well as the effect on metabolomics was investigated. All analyses are corrected for age, sex, body mass index, Townsend index for socioeconomic status, kcal, alcohol, protein intake, fat intake, carbohydrate intake, energy from beverages, diabetes, physical activity and for multiple testing. Results: We used a random forest classifier to analyse the feature importance of 63 nutrients and imaging‐proven steatosis in a cohort of over 25 000 UK Biobank participants. Increased dietary Mn intake was associated with a lower likelihood of MRI‐diagnosed steatosis. Subsequently, we conducted a cohort study in over 200 000 UK Biobank participants to explore the relationship between Mn intake and hepatic or cardiometabolic outcomes and found that higher Mn intake was associated with a lower risk of ICD‐10 coded steatosis (OR =.889 [.838–.943], p <.001), independent of other potential confounders. Conclusion: Our study provides evidence that higher Mn intake may be associated with lower odds of steatosis in a large population‐based sample. These findings underline the potential role of Mn in the prevention of steatosis, but further research is needed to confirm these findings and to elucidate the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Background & Aims: Metabolic dysfunction‐associated steatohepatitis (MASH) is a growing cause of chronic liver disease, characterized by fat accumulation, inflammation and fibrosis, which development depends on mitochondrial dysfunction and oxidative stress. Highly expressed in the liver during fasting, peroxisome proliferator‐activated receptor‐γ coactivator‐1α (PGC‐1α) regulates mitochondrial and oxidative metabolism. Given the relevant role of mitochondrial function in MASH, we investigated the relationship between PGC‐1α and steatohepatitis. Methods: We measured the hepatic expression of Pgc‐1α in both MASH patients and wild‐type mice fed a western diet (WD) inducing steatosis and fibrosis. We then generated a pure C57BL6/J strain loss of function mouse model in which Pgc‐1α is selectively deleted in the liver and we fed these mice with a WD supplemented with sugar water that accurately mimics human MASH. Results: We observed that the hepatic expression of Pgc‐1α is strongly reduced in MASH, in both humans and mice. Moreover, the hepatic ablation of Pgc‐1α promotes a considerable reduction of the hepatic mitochondrial respiratory capacity, setting up a bioenergetic harmful environment for liver diseases. Indeed, the lack of Pgc‐1α decreases mitochondrial function and increases inflammation, fibrosis and oxidative stress in the scenario of MASH. Intriguingly, this profibrotic phenotype is not linked with obesity, insulin resistance and lipid disbalance. Conclusions: In a MASH model the hepatic ablation of Pgc‐1α drives fibrosis independently from lipid and glucose metabolism. These results add a novel mechanistic piece to the puzzle of the specific and crucial role of mitochondrial function in MASH development. [ABSTRACT FROM AUTHOR]

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Background: Obesity, Western diet (WD) consumption, and the use of non-steroidal anti-inflammatory drugs (NSAIDs) are co-occurring and modifiable factors associated with microbiome dysbiosis and anastomotic leakage. We studied the combined effect of a Western-type diet (WD) and diclofenac, a standard NSAID used in surgical patients, on anastomotic healing and gut microbiota composition following distal colon resection. Methods: Forty-two rats were fed a WD for 6 weeks, after which they were randomized to either parenteral diclofenac 3 mg/kg/day or saline started on the day of surgery and continued for three days. The surgical procedure involved distal colon resection with anastomosis. Animals were sacrificed on postoperative day (POD)-3 or POD-5. Anastomotic healing was assessed and correlated with diclofenac treatment and gut microbiota composition, analyzed by 16S rRNA marker gene amplicon sequencing. Mucosal integrity of the anastomosis was evaluated by histological analysis. Results: Anastomotic leakage rate was 100 percent (8/8) in diclofenac-treated rats and 10 percent (1/10) in saline-treated controls on POD-5. Diclofenac administration in WD-fed animals induced a shift in microbiota composition, characterized by an increase in microbiota diversity on POD-5 and a significant 15-fold, 4-fold, and 16-fold increase of Proteobacteria, Bacteroidetes, and Verrucomicrobia, respectively. Diclofenac use in WD-fed animals caused mucosal erosion on POD-5, a phenomenon not observed in control animals. Conclusions: Consumption of a Western diet combined with diclofenac administration shifts the microbiota composition, associated with clinically relevant AL in the distal colon of rats. [ABSTRACT FROM AUTHOR]

Edible insects are considered among the most promising sustainable sources of protein to address the predicted deficiency of conventional food protein. Due to their nutritional and environmental benefits, there is an increasing interest in the ways insects could become part of the Western diet. Little is known about Greek consumers' attitudes toward the habit of consuming insects as food. This study provides insight into Greek consumers' preferences for insect-based food products. The data were collected through an online questionnaire (n = 1531). A two-step cluster analysis and a categorical regression were employed to classify the respondents into discernible clusters and determine the relationship between their socioeconomic characteristics and their willingness to adopt insect-based food products. Feelings of disgust and rejection were the predominant reactions to the concept of insects as food. The acceptance of novel foods derived from edible insects could be potentially enhanced by providing information regarding their positive effects, using familiar food products, and decreasing the insect's degree of visibility by employing processed forms. Finally, the categories of insect protein-enriched food products (bakery, meat, snacks) that Greek consumers are more likely to consume were revealed. Such findings may be useful for promoting strategies regarding consuming insect-based products. [ABSTRACT FROM AUTHOR]

Introduction and purpose: Lactose, the primary carbohydrate in milk, requires the enzyme lactase for digestion. Deficiency in lactase activity leads to lactose intolerance, causing gastrointestinal symptoms. Understanding the genetic and environmental factors influencing lactase expression and activity is crucial. Moreover, accurate diagnostic methods and effective treatments are needed to manage lactose intolerance. This review aims to explore the current knowledge on lactase deficiency, lactose intolerance, diagnostic methods, and treatment options. State of knowledge: Lactase deficiency encompasses congenital, primary, and secondary forms, each with distinct etiologies. Although often used interchangeably, lactase deficiency and lactose intolerance differ. However, the association between lactase deficiency and lactose intolerance is complex, influenced by various factors including dietary habits, gut microbiota, and gastrointestinal motility. Diagnostic methods are limited, and treatment strategies primarily involve dietary modifications, lactase supplementation, and probiotics. Conclusion: Lactose intolerance presents significant clinical challenges, often underrecognized and misdiagnosed. Despite diagnostic advancements further research is needed to refine diagnostic accuracy. Treatment focuses on dietary adjustments, enzyme supplementation, and probiotics. Balancing symptom relief with nutritional adequacy is essential. Future studies should explore the role of gut microbiome modulation in lactose intolerance management through clinical trials. [ABSTRACT FROM AUTHOR]

Western diets are the underlying cause of metabolic and liver diseases. Recent trend to limit the consumption of protein-rich animal products has become more prominent. This dietary change entails decreased protein consumption; however, it is still unknown how this affects innate immunity. Here, we studied the influence of a low protein diet (LPD) on the liver response to bacterial infection in mice. We found that LPD protects from Salmonella enterica serovar Typhimurium (S. Typhimurium)-induced liver damage. Bulk and single-cell RNA sequencing of murine liver cells showed reduced inflammation and upregulation of autophagy-related genes in myeloid cells in mice fed with LPD after S. Typhimurium infection. Mechanistically, we found reduced activation of the mammalian target of rapamycin (mTOR) pathway, whilst increased phagocytosis and activation of autophagy in LPD-programmed macrophages. We confirmed these observations in phagocytosis and mTOR activation in metabolically programmed human peripheral blood monocyte-derived macrophages. Together, our results support the causal role of dietary components on the fitness of the immune system. Low protein diet protects against Salmonella Typhimurium-mediated liver injury in mice corresponding to reduced mTOR activation and increased autophagy in macrophages. mTOR pathway activation with amino acid supplementation reverses this protection. [ABSTRACT FROM AUTHOR]

Seasonal rhythms are gaining attention given their impact on metabolic disorders development such as obesity gut microbiota is emerging as a key factor in mediating this link. However, the underlying mechanisms are still poorly understood. In this regard, corticosterone may play a role as it has been shown to be affected by gut bacteria and seasonal rhythms, and has been linked to obesity. Thus, this study aimed to investigate if seasonal rhythms effects on corticosterone are influenced by gut microbiota in obese rats and whether this may be related to seasonal and clock genes expression in the pituitary gland and colon. Fischer 344 male rats fed with cafeteria diet (CAF) were housed under different photoperiods for 9 weeks and treated with an antibiotic cocktail (ABX) in drinking water during the last 4 weeks. Rats fed with standard chow and CAF-fed rats without ABX were included as controls. ABX altered gut microbiota, corticosterone levels and seasonal clock expression in the pituitary depending on photoperiod conditions. These results suggest a link between gut bacteria, seasonal rhythms and corticosterone and a novel nutrigenomic target for obesity. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a prevalent aging disorder of synovial joints and recent work suggests that a parental high‐fat diet increases OA severity following joint injury in offspring. We hypothesized that a maternal high‐fat high‐sugar (HFHS) diet would promote spontaneous osteoarthritis‐related cartilage and bone changes in 1‐year‐old offspring. Female C57BL/6 J mice were placed on either a chow control or HFHS diet for 6 weeks before mating to a chow‐fed C57BL/6 J male and maintained on their assigned diets throughout pregnancy and lactation. Male and female offspring were weaned onto a chow diet, raised to 1 year of age, and evaluated for cartilage and bone changes indicative of OA. However, offspring did not show early signs of OA as measured by histological Mankin scoring, mechanical testing of the pericellular matrix, histological synovitis scoring, or subchondral bone thickening as measured by microcomputed Tomography. On the other hand, male offspring from HFHS‐fed dams had reduced trabecular bone quality in the tibial metaphysis and decreased cortical thickness. Although maternal HFHS diet did not impact trabecular or cortical bone quality in tibias of female offspring, the radii of these animals had decreased cortical thickness, increased medullary area, and impaired breaking strength compared to those of control‐fed dams. Finally, we evaluated bone quality and strength in male and female F2 offspring and found that the grandmaternal diet modestly impacted radial bone geometry but not strength. Together these results suggest that maternal HFHS diet impairs F1 offspring skeletal integrity in a sex and bone site‐specific manner. [ABSTRACT FROM AUTHOR]

Introduction: Blast injury has been implicated as the major cause of traumatic brain injury (TBI) and ocular system injury, in military operations in Iraq and Afghanistan. Soldiers exposed to traumatic stress also have undiagnosed, chronic vision problems. Here we hypothesize that excessive intake of ω-6 fatty acid linoleic acid (LA) and insufficiency of dietary long chain ω-3 polyunsaturated fatty acids (PUFAs, e.g., docosahexaenoic acid; DHA) would dysregulate endocannabinoid-mediated neuronal plasticity and immune response. The study objective was to determine the effect of blast-TBI and traumatic stress on retinal gene expression and assess the role of dietary deficiency of long chain ω-3 PUFAs on the vulnerability to these injury models. Methods: Linoleic acid was used as an independent variable to reflect the dietary increase in LA from 1 percent of energy (en%) to 8 en% present in the current western diets, and these custom LA diets were also devoid of long chain ω-3 PUFAs. Animals were exposed to a simulated blast overpressure wave followed by a weight drop head-concussion to induce TBI. A Separate group of rats were subjected to traumatic stress by a forced immersion underwater. Results: Our findings showed that blast-TBI exposure, post 14 days, produced significant neuropathological changes such as axonal degeneration in the brain optic tracts from all the three diet groups, especially in rats fed the DHA-deprived 1 en% LA diet. Transcriptomic analysis showed that presence of DHA in the house chow diet prevented blast-induced disruption of neuronal plasticity by activating molecular networks like SNARE signaling, endocannabinoid pathway, and synaptic long-term depression when compared to DHA-deprived 8 en% LA diet group. Under traumatic stress, retinal synaptic function, neurovascular coupling, and opioid signaling mechanisms were dysregulated in rodents fed DHA-deficient diets (i.e., 8 en% LA and 1 en% LA), where reducing the levels of ω-6 linoleic acid from 8 en% to 1 en% was associated with increased neuronal plasticity and suppressed immune signaling. Conclusion: The findings of our study suggest that deprivation of long chain ω-3 PUFAs in the diet affects endocannabinoid-mediated neuronal plasticity, vascular function and inflammatory response that could influence the resistance of veterans to TBI and psychological trauma. [ABSTRACT FROM AUTHOR]

Introduction: Sequelae from traumatic brain injuries (TBIs) and post-traumatic stress disorder (PTSD) are major career-limiting factors for combat soldiers. Overlap between TBI and PTSD symptoms alongside other common comorbidities complicate the diagnosis and treatment. Systems-level and high-throughput approaches are key in understanding the underlying biomolecular mechanisms and differentiating these conditions. Methods: The present study identifies dietary factors and proposes mechanisms behind psychological stress and TBI, using established preclinical animal models and a multi-omics approach. Here, we used microbiome characterizations of rats exposed to simulations of blast-induced TBI and underwater trauma (UWT)- induced psychological stress. We further studied the effect of dietary omega-6 versus omega-3 polyunsaturated fatty acid (n-6, n-3 PUFA) enrichment on the insult responses. The use of excess n-6 PUFA was chosen due to its high prevalence in the Western diet and pro-inflammatory nature. Prior to TBI or UWT, animals were maintained for 6 weeks and continued thereafter on either a standard diet or two customized chows imbalanced and diminished in omega-3 content. Corresponding shams were carried out for all groups. Fecal bacterial microbiome populations were assessed using 16S rRNA gene sequencing. Results: Physiologic outcome modeling identified that dietary status affected post-TBI lactate dehydrogenase (LDH) and triglyceride levels, with n-3 PUFA having a large attenuating influence. The UWT model showed similar trends, with diet significantly altering LDH, terminal corticosterone (14 days post-exposure), and a fear behavior susceptibility. Fecal microbiome alpha diversity was significantly reduced by high levels of n-3 PUFA. Likewise, beta diversity of the microbiome was significantly affected by both diet and time but not exposure to TBI or UWT. Compositionally, temporal effects on the microbiome were more likely to be observed with the diets. The most affected features fell within the Proteobacteria phyla, in which n-3 PUFA enrichment significantly reduced Alphaproteobacteria in the TBI model and increased Gammaproteobacteria in the UWT group. Discussion: All these observations can influence the vulnerability or resilience of the warfighter to blast-induced TBI and acute psychological stress. The microbiome mechanisms facilitate and provide a knowledge-driven unbiased panel of signatures to discriminate between the two insults and is an essential tool for designing precise care management. [ABSTRACT FROM AUTHOR]

Inflammatory bowel diseases (IBD), which enclose Crohn's disease (CD) and ulcerative colitis (UC), are chronic, relapsing inflammatory ailments. Their specific pathogenesis is not completely clarified, the worldwide incidence and prevalence of IBD has been steadily growing, and there is still not a definitive cure. The management of IBD has become more and more targeted, with specific immune mediators identified to be involved in its pathogenesis. Vedolizumab, a humanised monoclonal antibody binding specifically to the α4β7 integrin, is a gut-selective immunosuppressive biologic drug administered for both CD and UC. With the same indications as vedolizumab, ustekinumab is a fully human IgG1κ monoclonal antibody binding with specificity to the shared p40 protein subunit of human cytokines interleukin (IL)-12 and IL-23. Several selective IL-23p19 monoclonal antibodies (risankizumab, mirikizumab, and guselkumab) have also revealed admirable efficacy and safety in IBD patients. Nutrition is a very important environmental factor associated with the onset and progression of IBD, and the Western diet is considered to contribute to the development of IBD. In this narrative review, our aim is to present an overview of the main results from recent clinical studies on IBD regarding diet, new drug treatments, and also vaccination. [ABSTRACT FROM AUTHOR]

Following bowel surgery, infectious complications, including anastomotic leak (AL), remain major sources of morbidity and mortality. Bowel preparation is often administered with the assumption that gut decontamination reduces post-surgical complications. In this study, we tested this hypothesis using a murine model of colon surgery. The mice were fed either regular chow or a high-fat, high-sugar Western diet. The day before surgery, the mice received one of four interventions: water (control), mechanical bowel preparation (MBP), oral antibiotics (OA), or both MBP and OA. We found no differences in the rates of AL among the experimental groups, and diet did not appear to affect the outcomes. Exploratory analyses showed changes in the gut microbiome consistent with the different treatments, but investigations of fecal short-chain fatty acids and RNA sequencing of colonic tissue did not reveal specific effects of the treatments or the presence of AL. However, we did identify bacterial genera that may be causally associated with AL and developed a predictive index from stool samples as a marker for the presence of AL. Future research is needed to identify and validate a microbial predictive tool and to uncover the microbial-driven mechanisms that lead to AL. [ABSTRACT FROM AUTHOR]

Introduction: Matcha, a finely powdered form of green tea, has recently gained global popularity due to its vibrant green color, distinctive taste, and versatile applications in various food products. Despite its promising nutritional profile, matcha has not received significant attention in the academic community compared to traditional green tea. Purpose of work: The primary objective of this review is to provide a comprehensive overview of the current understanding of matcha's biological properties and its potential health benefits. Methods and materials: A review of the literature available in the PubMed database and Google Scholar, the following keywords were searched: "matcha", "catechin", "EGCG", "cognitive function", "green tea" State of knowledge: Existing studies have demonstrated that matcha exhibits anticancer properties, enhances cognitive function, improves cardio-metabolic health, and modulates the gut microbiome. Moreover, matcha is known for its anti-inflammatory and antioxidant properties. Summary: This review summarizes the latest research findings on matcha green tea and its potential health benefits. While animal studies have shown promising results, our knowledge of matcha's effects on human health remains limited. Further randomized controlled trials are necessary to fully elucidate its potential health-promoting effects. Therefore, we advocate for continued research into matcha's properties and its integration into dietary practices to promote overall health and well-being. [ABSTRACT FROM AUTHOR]

Background: Systemic Lupus Erythematosus (SLE) has a strong genetic susceptibility, but little is known about the impact of diet on disease severity. The Western diet is typically deficient in magnesium (Mg), and given the immunomodulatory effects of Mg, we hypothesized that the low Mg intake increases disease risk and that increasing Mg intake would reduce severity of murine lupus. Here, we placed 12-week old MRL/lpr female lupus mice on a normal (Mg500) or a high (Mg2800) Mg diet for 9 weeks. Urine and blood were collected during the study for quantification of urinary albumin, BUN, anti-dsDNA antibodies, and immune phenotyping. Results: MRL/lpr lupus mice on high Mg2800 diet had significantly fewer skin lesions and less severe skin histology score, and reduced levels of pathogenic anti-dsDNA antibodies, compared with the Mg500 group (143.8±75.0 vs. 47.4±36.2 × 106U/ml; P < 0.05). The high Mg2800 group had a nearly two-fold increase in the percentage of CD4+FOXP3+ Treg cells compared to controls (19.9±5.4 vs. 11.4±5.5%; P < 0.05). Treg percentages inversely correlated with the concentration of anti-dsDNA. None of the mice developed arthritis during the observation period and there were no significant differences in weight, proteinuria, BUN or kidney histology. Conclusion: In conclusion, oral supplementation of Mg has a protective effect in a murine lupus model and may represent an inexpensive and safe adjuvant in the treatment of SLsE. [ABSTRACT FROM AUTHOR]

This document is a compilation of articles from the Journal of Gastroenterology & Hepatology that cover various topics related to nutrition and gastrointestinal health. The articles provide insights into risk factors for infections in patients receiving home nutrition, the quality of life of patients using home nutrition, energy and protein requirements for adults with ulcerative colitis, the use of a specific surgical procedure in patients with gastroparesis, and the content of oral nutrition supplements in Australia. The articles also discuss the impact of the Mediterranean diet on cancer risk and survivorship, the association between ultra-processed foods and mortality and dementia in older adults, and the potential influence of diet on primary sclerosing cholangitis. Additionally, the articles explore the practical application of evidence-based dietary therapy for inflammatory bowel disease, the usage and complications of peripheral parenteral nutrition, the need for improved nutritional assessment tools for patients with liver cirrhosis, and the relationship between dietary intake and disease activity in adults with inflammatory bowel disease. The articles emphasize the importance of diet and nutrition in overall health and highlight the need for further research in various areas. [Extracted from the article]

Changes in dietary patterns towards Western diets, along with unhealthy lifestyles, are causing a rapid increase in the rates of overweight, obesity, and noncommunicable chronic diseases in the Peruvian population. Food-based dietary guidelines (FBDG) are supportive tools for public policies aimed at promoting healthier eating habits. This study aimed to present the process of designing and validating an iconography for the Peru FBDG. The design process involved an extensive review of dietary iconography in various countries of the LAC region. In accordance with the specific context of Peru, the decision was made to incorporate local elements into the iconography. Four image proposals were initially designed and subsequently subjected to expert validation. From these, two proposals were selected for population validation through focus groups. The validation process focused on qualitative evaluation criteria, including understanding, attraction, involvement, acceptance, and induction to action. The resulting final iconography consists of two concentric circles. The central circle represents the seven food groups distributed proportionally, while the outer circle signifies healthy lifestyles, encompassing physical activity, commensality, and daily water consumption, portrayed in vibrant colors. Surrounding the circles are icons representing ultraprocessed foods depicted in black octagons. Additionally, icons for added sugar and salt are placed outside the circles, serving as prominent warnings to reduce their consumption, as recommended during the validation process. This study successfully developed an iconographic representation that fulfills both technical and population-level validation criteria. The incorporation of participants' contributions and recommendations further enhanced its efficacy. The validated iconography not only serves as an educational and awareness tool but also offers practical guidance for individuals to adopt healthier dietary practices and lifestyles. In conclusion, the FBDG iconography effectively communicated the importance of natural foods over ultra-processed ones, along with emphasizing healthy eating habits, as understood and embraced by focus group participants. The attraction and comprehension of the FBDG iconography looks promising for its implementation, suggesting improvements in the health and nutritional well-being of individuals of two years and above. [ABSTRACT FROM AUTHOR]

The human gastrointestinal tract hosts a complex and dynamic community of microorganisms known as the gut microbiota, which play a pivotal role in numerous physiological processes, including digestion, metabolism, and immune function. Recent research has highlighted the significant impact of diet on the gut microbiota composition and functionality, and the consequential effects on host health. Concurrently, there is growing evidence linking the gut microbiota to inflammation, a key factor in many chronic diseases such as inflammatory bowel disease (IBD), obesity, diabetes, and cardiovascular diseases (CVDs). This review explores how dietary components influence the gut microbiota composition, how these microbial changes affect inflammatory pathways, and the therapeutic implications of modulating this axis for chronic inflammatory disease prevention and management. Beneficial dietary patterns, such as the Mediterranean diet (MD) and plant-based diets, promote a diverse and balanced gut microbiota composition, supporting anti-inflammatory pathways. Conversely, the Western diet (WD), high in saturated fats and refined sugars, is associated with dysbiosis and increased inflammation. With all the links between the three variables considered, this review attempts to offer a thorough examination of the triangle formed by inflammation, the gut microbiota, and food. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to investigate the effects of different ω-3 polyunsaturated fatty acid (PUFA) enriched diets, including a novel renewable plant source of ω-3 fatty acids (Buglossoides arvensis), on the development and progression of rheumatoid arthritis (RA). Methods: RA was induced in mice consuming experimental diets using the K/BxN model. The experimental diets consisted of either a western control diet (control), diets containing B. arvensis oil or fish oil. The effects of the diets on platelets, platelet microvesicles (PMVs), and inflammatory markers such as clinical index, ankle thickness and cytokine/chemokine release were measured. Results: While ω-3 PUFA-enriched diets did not prevent the development of arthritis in the K/BxN model, a significant decrease in ankle swelling was observed compared to the control group. Platelets isolated from mice consuming either low content of B. arvensis oil or fish oil diets exhibited significantly decreased PMVs production compared to mice consuming the control diet. Conclusion: Our study provides insight into the contribution of ω-3 PUFA supplementation in modulating the pro-inflammatory phenotype of platelets in RA pathology. Furthermore, our study suggests that low concentrations of dietary B. arvensis oil may have similar anti-inflammatory potential seen with dietary fish oil supplementation. [ABSTRACT FROM AUTHOR]

Maternal exposure to endocrine-disrupting chemicals (EDCs) in human pregnancy is widely considered as an important cause of adverse changes in male reproductive health due to impaired foetal androgen production/action. However, the epidemiological evidence supporting this view is equivocal, except for certain phthalates, notably diethyl hexyl phthalate (DEHP). Maternal phthalate exposure levels associated with adverse reproductive changes in epidemiological studies are several thousand-fold lower than those needed to suppress foetal androgen production in rats, and direct studies using human foetal testis tissue show no effect of high phthalate exposure on androgen production. This conundrum is unexplained and raises fundamental questions. Human DEHP exposure is predominantly via food with highest exposure associated with consumption of a Western style (unhealthy) diet. This diet is also associated with increased exposure to the most common EDCs, whether persistent (chlorinated or fluorinated chemicals) or non-persistent (phthalates, bisphenols) compounds, which are found at highest levels in fatty and processed foods. Consequently, epidemiological studies associating EDC exposure and male reproductive health disorders are confounded by potential dietary effects, and vice versa. A Western diet/lifestyle in young adulthood is also associated with low sperm counts. Disentangling EDC and dietary effects in epidemiological studies is challenging. In pregnancy, a Western diet, EDC exposure, and maternal living in proximity to industrial sites are all associated with impaired foetal growth/development due to placental dysfunction, which predisposes to congenital male reproductive disorders (cryptorchidism, hypospadias). While the latter are considered to reflect impaired foetal androgen production, effects resulting from foetal growth impairment (FGI) are likely indirect. As FGI has numerous life-long health consequences, and is affected by maternal lifestyle, research into the origins of male reproductive disorders should take more account of this. Additionally, potential effects on foetal growth/foetal testis from the increasing use of medications in pregnancy deserves more research attention. [ABSTRACT FROM AUTHOR]

The aim of this literature review was to identify and provide a summary update on the validity and applicability of the most promising dietary biomarkers reflecting the intake of important foods in the Western diet for application in epidemiological studies. Many dietary biomarker candidates, reflecting intake of common foods and their specific constituents, have been discovered from intervention and observational studies in humans, but few have been validated. The literature search was targeted for biomarker candidates previously reported to reflect intakes of specific food groups or components that are of major importance in health and disease. Their validity was evaluated according to 8 predefined validation criteria and adapted to epidemiological studies; we summarized the findings and listed the most promising food intake biomarkers based on the evaluation. Biomarker candidates for alcohol, cereals, coffee, dairy, fats and oils, fruits, legumes, meat, seafood, sugar, tea, and vegetables were identified. Top candidates for all categories are specific to certain foods, have defined parent compounds, and their concentrations are unaffected by nonfood determinants. The correlations of candidate dietary biomarkers with habitual food intake were moderate to strong and their reproducibility over time ranged from low to high. For many biomarker candidates, critical information regarding dose response, correlation with habitual food intake, and reproducibility over time is yet unknown. The nutritional epidemiology field will benefit from the development of novel methods to combine single biomarkers to generate biomarker panels in combination with self-reported data. The most promising dietary biomarker candidates that reflect commonly consumed foods and food components for application in epidemiological studies were identified, and research required for their full validation was summarized. [ABSTRACT FROM AUTHOR]

Potassium is a cation involved in the resting phase of membrane potential. Diets rich in fresh fruit and vegetables, whole grains, dairy products, and coffee have high potassium content. The shift from a pre-agriculture diet to today's consumption has led to reduced potassium intake. Indeed, the Western diet pattern is characterized by a high daily intake of saturated fats, sugars, sodium, proteins from red meat, and refined carbohydrates with a low potassium intake. These reductions are also mirrored by high sodium intakes and a high consumption of acid-generating food, which promote a chronic state of low-grade metabolic acidosis. The low-grade metabolic acidosis is a cause of the bone-wasting effect. Therefore, a long-standing acidotic state brings into play the bone that contributes to the buffering process through an increase in osteoclastic resorption. In consideration of this background, we carried out a review that focused on the pathophysiological mechanisms of the relationship between dietary potassium intake and bone health, underlining the detrimental effects of the Western dietary patterns characterized by low potassium consumption. [ABSTRACT FROM AUTHOR]

Firefighters have demanding jobs, requiring high levels of fitness in stressful situations for operational readiness, yet many firefighters are at an increased risk of developing cardiovascular disease (CVD). Diet is an important factor contributing to the development of CVD. The purpose of this study was to describe the dietary intake of firefighters and examine the associations between dietary intake and the CVD risk. Forty-six male career firefighters (age = 41.2 ± 11.2 years; BMI = 29.2 ± 4.1 kg/m2; body fat = 21.7 ± 6.1%) enrolled in a fitness-focused wellness program completed a health survey and a fitness assessment. The survey responses and fitness assessment were used to calculate the Framingham CVD Risk Score. Data were analyzed using R, the residual assumptions were verified, and the alpha level was set at 0.05. The results revealed that firefighters consume a standard American diet, with the overconsumption of meat and underconsumption of fruits and vegetables. The average CVD risk approached the upper limit of low risk. The results also indicate that meat servings and preparation fat affect the CVD risk (R2 = 0.21, p = 0.006). The outcomes of this study can inform investigations aimed at improving operational readiness and reducing the CVD risk in firefighters by implementing a holistic approach combining dietary interventions with physical training. [ABSTRACT FROM AUTHOR]

Advanced glycation end products (AGEs) are formed by the Maillard reaction, a nonenzymatic process that occurs widely in cooking, food processing, and within the human body. Primarily, AGEs are formed by the glycation of reducing sugars with amino groups, and this process is heat‐dependent. With changes in lifestyle, there has been an increase in the diversity of dietary habits, including those patterns associated with Western diets, which include the consumption of processed foods that are rich in AGEs. Excessive intake and exposure to AGEs are known to cause abnormalities in body function such as obesity, diabetes, and fatty liver, and the beneficial effects of AGEs in food processing in improving food flavor and quality. To obtain meaningful data regarding AGEs in a variety of food and human samples, it is necessary to more precisely characterize and analyze the AGEs extracted from samples to obtain accurate results. This review explores the recent analytical research and characterization of AGEs in foods, including casein, β‐lactoglobulin, soy protein, and meat protein, and in human samples, such as glycated‐albumin, hemoglobin, and plasma. Additionally, it explores the metabolic fate of AGEs in the body and the mechanisms of disease associated with metabolic abnormalities that may be caused by the consumption of foods containing AGEs. This review aims to provide an overview of the perspectives of relevant recent and future research on metabolic abnormalities caused by foods containing AGEs or by AGEs produced in the body. [ABSTRACT FROM AUTHOR]

Diet‐induced obesity is associated with enhanced systemic inflammation that limits bone regeneration. HDAC inhibitors are currently being explored as anti‐inflammatory agents. Prior reports show that myeloid progenitor‐directed Hdac3 ablation enhances intramembranous bone healing in female mice. In this study, we determined if Hdac3 ablation increased intramembranous bone regeneration in mice fed a high‐fat/high‐sugar (HFD) diet. Micro‐CT analyses demonstrated that HFD‐feeding enhanced the formation of periosteal reaction tissue of control littermates, reflective of suboptimal bone healing. We confirmed enhanced bone volume within the defect of Hdac3‐ablated females and showed that Hdac3 ablation reduced the amount of periosteal reaction tissue following HFD feeding. Osteoblasts cultured in a conditioned medium derived from Hdac3‐ablated cells exhibited a four‐fold increase in mineralization and enhanced osteogenic gene expression. We found that Hdac3 ablation elevated the secretion of several chemokines, including CCL2. We then confirmed that Hdac3 deficiency increased the expression of Ccl2. Lastly, we show that the proportion of CCL2‐positve cells within bone defects was significantly higher in Hdac3‐deficient mice and was further enhanced by HFD. Overall, our studies demonstrate that Hdac3 deletion enhances intramembranous bone healing in a setting of diet‐induced obesity, possibly through increased production of CCL2 by macrophages within the defect. [ABSTRACT FROM AUTHOR]

Abstract Following bowel surgery, infectious complications, including anastomotic leak (AL), remain major sources of morbidity and mortality. Bowel preparation is often administered with the assumption that gut decontamination reduces post-surgical complications. In this study, we tested this hypothesis using a murine model of colon surgery. The mice were fed either regular chow or a high-fat, high-sugar Western diet. The day before surgery, the mice received one of four interventions: water (control), mechanical bowel preparation (MBP), oral antibiotics (OA), or both MBP and OA. We found no differences in the rates of AL among the experimental groups, and diet did not appear to affect the outcomes. Exploratory analyses showed changes in the gut microbiome consistent with the different treatments, but investigations of fecal short-chain fatty acids and RNA sequencing of colonic tissue did not reveal specific effects of the treatments or the presence of AL. However, we did identify bacterial genera that may be causally associated with AL and developed a predictive index from stool samples as a marker for the presence of AL. Future research is needed to identify and validate a microbial predictive tool and to uncover the microbial-driven mechanisms that lead to AL.

Abstract Seasonal rhythms are gaining attention given their impact on metabolic disorders development such as obesity gut microbiota is emerging as a key factor in mediating this link. However, the underlying mechanisms are still poorly understood. In this regard, corticosterone may play a role as it has been shown to be affected by gut bacteria and seasonal rhythms, and has been linked to obesity. Thus, this study aimed to investigate if seasonal rhythms effects on corticosterone are influenced by gut microbiota in obese rats and whether this may be related to seasonal and clock genes expression in the pituitary gland and colon. Fischer 344 male rats fed with cafeteria diet (CAF) were housed under different photoperiods for 9 weeks and treated with an antibiotic cocktail (ABX) in drinking water during the last 4 weeks. Rats fed with standard chow and CAF-fed rats without ABX were included as controls. ABX altered gut microbiota, corticosterone levels and seasonal clock expression in the pituitary depending on photoperiod conditions. These results suggest a link between gut bacteria, seasonal rhythms and corticosterone and a novel nutrigenomic target for obesity.

Abstract Cardiovascular-kidney-metabolic health reflects the interactions between metabolic risk factors, chronic kidney disease, and the cardiovascular system. A growing body of literature suggests that metabolic syndrome (MetS) in individuals of normal weight is associated with a high prevalence of cardiovascular diseases and an increased mortality. The aim of this study was to establish a non-invasive preclinical model of MetS in support of future research focusing on the effects of novel antidiabetic therapies beyond glucose reduction, independent of obesity. Eighteen healthy adult Beagle dogs were fed an isocaloric Western diet (WD) for ten weeks. Biospecimens were collected at baseline (BAS1) and after ten weeks of WD feeding (BAS2) for measurement of blood pressure (BP), serum chemistry, lipoprotein profiling, blood glucose, glucagon, insulin secretion, NT-proBNP, angiotensins, oxidative stress biomarkers, serum, urine, and fecal metabolomics. Differences between BAS1 and BAS2 were analyzed using non-parametric Wilcoxon signed-rank testing. The isocaloric WD model induced significant variations in several markers of MetS, including elevated BP, increased glucose concentrations, and reduced HDL-cholesterol. It also caused an increase in circulating NT-proBNP levels, a decrease in serum bicarbonate, and significant changes in general metabolism, lipids, and biogenic amines. Short-term, isocaloric feeding with a WD in dogs replicated key biological features of MetS while also causing low-grade metabolic acidosis and elevating natriuretic peptides. These findings support the use of the WD canine model for studying the metabolic effects of new antidiabetic therapies independent of obesity.

Abstract Dietary biomarkers in urine remain elusive when evaluating diet-induced oxidative stress and inflammation. In our previous study, we conducted a randomized controlled crossover trial to compare the short-term (4-weeks) effects of the balanced Korean diet (BKD) with Western diets, including the 2010 dietary guidelines for Americans (2010 DGA) and typical American diet (TAD), on various metabolic indices in obese Korean adults. Building on this work, the current research focuses on the impact of these dietary interventions on oxidative stress (d-ROMs and BAP) and inflammation (CRP, TNF-α, IL-6, IL-1β, MCP-1) biomarkers in serum, and the concurrent urine metabolomes. Each dietary regimen was in silico and experimentally examined for their antioxidant levels using ABTS, DPPH, and FRAP assays, as well as total flavonoid (TFC) and total phenolic (TPC) contents. We assessed post-intervention variations in oxidative stress and inflammation biomarkers in serum, as well as the urine metabolite profiles for the participants (n = 48, average age: 41 years). Antioxidant contents and associated total antioxidant capacity (TAC) were significantly higher for the recommended diets (BKD and 2010 DGA) compared to TAD (p 0.7, p

Abstract Several risk factors including environmental exposures, socioeconomic status, and dietary factors including dietary patterns have been considered for childhood Asthma. The present study tried to examine the association between a western-style pattern and the likelihood of asthma and its symptoms in Yazd, Iran. In the present cross-sectional study, dietary intakes of elementary and high-school children were obtained through a validated GAN questionnaire. The GAN questionnaire, derived from the ISAAC questionnaire was used to assess the symptoms of allergic diseases and their related risk factors. A western dietary pattern score considered 9 food groups including chicken eggs, margarine, butter, sugar, fast foods, soft drinks, snacks, sauce, and chocolate. In total 7667 children aged 10.9 ± 3.35 years were included in the current investigation. Boys with higher adherence to western dietary pattern had a higher risk of wheezing in the past 12 months (OR 1.37, 5% CI 1.01–1.87, P = 0.04) and this association was also observed in the whole population (OR 1.30, 5% CI 1.05–1.60, P = 0.01). However, after adjustment for confounders this relation did not remain significant in boys. Our results support the hypothesis that a western dietary pattern is associated with an increased risk of wheezing in the past 12 months in children with asthma. Future prospective studies are needed to confirm this finding.

Background: Recent studies provide increasing evidence for a relevant role of lifestyle factors including diet in the pathogenesis of neuroinflammatory diseases such as multiple sclerosis (MS). While the intake of saturated fatty acids and elevated salt worsen the disease outcome in the experimental model of MS by enhanced inflammatory but diminished regulatory immunological processes, sugars as additional prominent components in our daily diet have only scarcely been investigated so far. Apart from glucose and fructose, galactose is a common sugar in the so-called Western diet. Methods: We investigated the effect of a galactose-rich diet during neuroinflammation using myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (MOG-EAE) as a model disease. We investigated peripheral immune reactions and inflammatory infiltration by ex vivo flow cytometry analysis and performed histological staining of the spinal cord to analyze effects of galactose in the central nervous system (CNS). We analyzed the formation of advanced glycation end products (AGEs) by fluorescence measurements and investigated galactose as well as galactoseinduced AGEs in oligodendroglial cell cultures and induced pluripotent stem cellderived primary neurons (iPNs). Results: Young mice fed a galactose-rich diet displayed exacerbated disease symptoms in the acute phase of EAE as well as impaired recovery in the chronic phase. Galactose did not affect peripheral immune reactions or inflammatory infiltration into the CNS, but resulted in increased demyelination, oligodendrocyte loss and enhanced neuro-axonal damage. Ex vivo analysis revealed an increased apoptosis of oligodendrocytes isolated from mice adapted on a galactose-rich diet. In vitro, treatment of cells with galactose neither impaired the maturation nor survival of oligodendroglial cells or iPNs. However, incubation of proteins with galactose in vitro led to the formation AGEs, that were increased in the spinal cord of EAE-diseased mice fed a galactose-rich diet. In oligodendroglial and neuronal cultures, treatment with galactose-induced AGEs promoted enhanced cell death compared to control treatment. Conclusion: These results imply that galactose-induced oligodendrocyte and myelin damage during neuroinflammation may be mediated by AGEs, thereby identifying galactose and its reactive products as potential dietary risk factors for neuroinflammatory diseases such as MS. [ABSTRACT FROM AUTHOR]

The two major determining factors for Alzheimer's disease (AD) are genetics and lifestyle. Alleles of the apolipoprotein E (APOE) gene play important roles in the development of late-onset AD, with APOEɛ4 increasing risk, APOEɛ3 being neutral, and APOEɛ2 reducing risk. Several modifiable lifestyle factors have been studied in terms of how they can modify the risk of AD. Among these factors are dietary pattern, nutritional supplements such as omega-3 fatty acids, and B vitamins, physical exercise, and obesity, and vitamin D. The Western diet increases risk of AD, while dietary patterns such as the Mediterranean and vegetarian/vegan diets reduce risk. Foods associated with reduced risk include coffee, fruits and vegetables, whole grains and legumes, and fish, while meat and ultraprocessed foods are associated with increased risk, especially when they lead to obesity. In multi-country ecological studies, the amount of meat in the national diet has the highest correlation with risk of AD. The history of research regarding dietary patterns on risk of AD is emphasized in this review. The risk of AD can be modified starting at least by mid-life. People with greater genetic risk for AD would benefit more by choosing lifestyle factors to reduce and/or delay incidence of AD. [ABSTRACT FROM AUTHOR]

Background: Activation of brown adipose tissue (BAT) has gained attention due to its ability to dissipate energy and counteract cardiometabolic diseases (CMDs). Methods: This study investigated the consequences of cold exposure on the BAT and liver proteomes of an established CMD mouse model based on LDL receptor-deficient (LdlrKO) mice fed a high-fat, high-sucrose, high-cholesterol diet for 16 weeks. We analyzed energy metabolism in vivo and performed untargeted proteomics on BAT and liver of LdlrKO mice maintained at 22 °C or 5 °C for 7 days. Results: We identified several dysregulated pathways, miRNAs, and transcription factors in BAT and liver of cold-exposed Ldlrko mice that have not been previously described in this context. Networks of regulatory interactions based on shared downstream targets and analysis of ligand-receptor pairs identified fibrinogen alpha chain (FGA) and fibronectin 1 (FN1) as potential crosstalk factors between BAT and liver in response to cold exposure. Importantly, genetic variations in the genes encoding FGA and FN1 have been associated with cardiometabolic-related phenotypes and traits in humans. Discussion: This study describes the key factors, pathways, and regulatory networks involved in the crosstalk between BAT and the liver in a cold-exposed CMD mouse model. These findings may provide a basis for future studies aimed at testing whether molecular mediators, as well as regulatory and signaling mechanisms involved in tissue adaption upon cold exposure, could represent a target in cardiometabolic disorders. [ABSTRACT FROM AUTHOR]

The prevalence of obesity and related consequences, including insulin resistance and Alzheimer's-like neuropathology, has increased dramatically. Contributing to this prevalence is the shift in lifestyle preference away from wholesome foods and exercise to the Western-style diet and sedentarism. Despite advances in drug development, a healthy diet and regular exercise remain the most effective approaches to mitigating the unwanted sequelae of diet-induced obesity on brain health. In this study, we used the high-fat high-sugar (HFHS) mouse model of neurodegeneration to examine the effects of exercise training (HFHS+Ex), genistein treatment (HFHS+Gen), and combination treatment (HFHS+Ex+Gen) on proteins relating to neurodegeneration in the brain of male mice. After a period of 12 weeks, as expected, HFHS feeding increased body weight, adipose tissue weight, and systemic plasma inflammation (TNF-α) compared to lean mice fed a standard diet. HFHS feeding also increased protein expression of brain markers of insulin resistance (pGSK-3β, p-IR), apoptosis (caspase 3), early neurofibrillary tangles (CP13), and amyloid-beta precursor (CT20). Compared to HFHS mice, Ex decreased body weight, plasma TNF-α, and expression of pGSK-3β, caspase 3, CP13, amyloid-β precursor (22c11), and ADAM10. Treatment with Gen was equally protective on these markers and decreased the expression of p-IR. Combination treatment with Ex and Gen afforded the greatest overall benefits, and this group exhibited the greatest reduction in body and adipose tissue weight and all brain markers, except for 22c11 and ADAM10, which were decreased compared to mice fed an HFHS diet. In addition, levels of 4G8, which detects protein levels of amyloid-β, were decreased with combination treatment. Our results indicate that exercise training, genistein supplementation, or combination treatment provide varying degrees of neuroprotection from HFHS feeding-induced Alzheimer's pathology. Future perspectives could include evaluating moderate exercise regimens in combination with dietary supplementation with genistein in humans to determine whether the same benefits translate clinically. [ABSTRACT FROM AUTHOR]