Elafibranor, a dual PPARα and PPARδ agonist, reduces alcohol-associated liver disease: Lessons from a mouse model.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent liver pathology in need of novel pharmacological treatments to complement lifestyle-based interventions. Nuclear receptor agonists have been under scrutiny as potential pharmacological targets and as of today, resmetirom, a thyroid hormone receptor b agonist, is the only approved agent. The dual PPAR α and δ agonist elafibranor has also undergone extensive clinical testing, which reached the phase III clinical trial but failed to demonstrate a beneficial effect on MASLD.

The Similarity Degree of the Anthropometric and Body Composition Variables of Brazilian and Mozambican Schoolchildren: A New Approach Using the Smoothed Jaccard Index Surface.

Background/objectives: Brazil and Mozambique face similar socioeconomic challenges, including common indicators of undernutrition and overnutrition among children. This study evaluated the similarity degree of the anthropometric and body composition variables of Brazilian and Mozambican children by using the Jaccard index.

Methods: A total of 1831 children of both genders aged 7-10 years from three Brazilian cities (Recife, Vitoria de Santo Antao, and Lagoa do Carro) and three Mozambican cities (Maputo, Boane, and Inhambane) participated in this study.

Adipose stem cells drive T cell infiltration in obesity.

Obesity is often associated with adipose tissue (AT) inflammation and immune cell infiltration. Writing recently in Cell Reports, Liao et al. investigated the mechanisms of T cell infiltration of AT using single cell (sc)RNA-sequencing (RNA-seq), transplantation studies, in vitro co-cultures, and knock-out mice.

Association between Childhood Overweight and Altered Concentrations of Circulating Amino Acids.

(1) Background: Dysregulated serum amino acids (AA) are known to be associated with obesity and risk of Type 2 Diabetes (T2D) in adults, and recent studies support the same notion in the pubertal age. It is, however, unknown whether childhood overweight may already display alterations of circulating AA. (2) Methods: We used liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS)-targeted metabolomics to determine plasma concentrations of AA and AA-related molecules in 36 children aged 7-12 years with normal weight or overweight.

Ultrasound muscle assessment for sarcopenia detection in inflammatory bowel disease: A prospective study.

Background: Sarcopenia is prevalent in patients with inflammatory bowel disease (IBD) and impacts surgical and therapeutic outcomes; thus, effective diagnostic tools are needed to assess muscle mass and function in this population.

Methods: 153 consecutive patients were included, 100 in the training cohort and 53 in the study cohort. Three superficial muscles (rectus femoris = RF, rectus abdominis = RA, and biceps brachii = BB) were selected for the detection of sarcopenia using muscle ultrasound (US).

Peptidylarginine Deiminases Inhibitors Decrease Endothelial Cells Angiogenic Potential by Affecting Akt Signaling and the Expression and Secretion of Angiogenic Factors.

Background/aims: Endothelial cells (ECs) play a crucial role in various physiological processes, particularly those related to the cardiovascular system, but also those affecting the entire organism. The biology of ECs is regulated by multiple biochemical stimuli and epigenetic drivers that govern gene expression. We investigated the angiogenic potential of ECs from a protein citrullination perspective, regulated by peptidyl-arginine deiminases (PADs) that modify histone and non-histone proteins.

Diet enriched in saturated fatty acids induces liver oxidative stress and elicits inflammatory pathways prior to metabolic disruption in perinatal protein undernutrition.

The impact of diets high in saturated fatty acids in individuals who have undergone maternal protein restriction is not clear. Here, we tested the hypothesis that a saturated fatty acid-enriched hyperlipidic diet (HL) affects liver expression of genes of the redox balance and inflammatory pathway in postweaning rat offspring subjected to maternal protein restriction. Pregnant Wistar rats received either a control (C; 19% protein) or low protein (LP; 8% protein) diet during gestation and lactation.

Adipokines in obesity and metabolic-related-diseases.

The discovery of leptin in the 1990s led to a reconsideration of adipose tissue (AT) as not only a fatty acid storage organ, but also a proper endocrine tissue. AT is indeed capable of secreting bioactive molecules called adipokines for white AT or batokines for brown/beige AT, which allow communication with numerous organs, especially brain, heart, liver, pancreas, and/or the vascular system. Adipokines exert pro or anti-inflammatory activities.

Inflammation and malnutrition in inflammatory bowel disease.

Inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis, has become increasingly prevalent worldwide in the past decade. The nutritional status of patients with IBD is often impaired, with malnutrition presenting as imbalanced energy or nutrient intake, including protein-energy malnutrition, disease-related malnutrition, sarcopenia, and micronutrient deficiency. Additionally, malnutrition can manifest as overweight, obesity, and sarcopenic obesity.

Ketone Bodies as Metabolites and Signalling Molecules at the Crossroad between Inflammation and Epigenetic Control of Cardiometabolic Disorders.

For many years, it has been clear that a Western diet rich in saturated fats and sugars promotes an inflammatory environment predisposing a person to chronic cardiometabolic diseases. In parallel, the emergence of ketogenic diets, deprived of carbohydrates and promoting the synthesis of ketone bodies imitating the metabolic effects of fasting, has been shown to provide a possible nutritional solution to alleviating diseases triggered by an inflammatory environment. The main ketone body, β-hydroxybutyrate (BHB), acts as an alternative fuel, and also as a substrate for a novel histone post-translational modification, β-hydroxybutyrylation.

Fat not so bad? The role of ketone bodies and ketogenic diet in the treatment of endothelial dysfunction and hypertension.

The ketogenic diet (KD), a high-fat, low-carbohydrate dietary approach that is based on the induction of extensive ketone bodies (KB) metabolism, is recently receiving a lot of attention due to its application as effective intervention for multiple metabolic disorders including cardiovascular diseases. Despite its already established clinical use, especially in the treatment of drug-resistant epilepsy, GLUT1 deficiency syndromes and, in selected cases, obesity; the systemic impact of is not yet fully understood. Here, we discuss the evidence for and against the application of ketogenic diets, or ketone bodies precursors, in the etiology of hypertension and endothelial cells dysfunction.

Food consumption habits, gestational age and birth weight are predictive for children with excess weight: An analysis based on artificial neural network.

The relationship between body weight gain and the onset of obesity is linked to environmental and behavioral factors, and may be dependent on biological predisposing. Artificial neural networks are useful predictive tools in the field of artificial intelligence, and can be used to identify risk factors related to obesity. The aim of this study is to establish, based on artificial neural networks, a predictive model for overweight/obesity in children based on the recognition and selection of patterns associated with birth weight, gestational age, height deficit, food consumption, and the physical activity level, TV time and family context.

Use of IBD Drugs in Patients With Hepatobiliary Comorbidities: Tips and Tricks.

Advanced therapies (biologic agents and small molecules) for inflammatory bowel diseases (IBD) have radically changed the management of these diseases during the last decade. Data about these drugs in patients with hepatic disorders derive mainly from real-life studies, as these conditions often represent an exclusion criterion from pivotal drug developmental trials. However, IBD patients sometimes have concomitant liver diseases.

Ketogenic diet administration to mice after a high-fat-diet regimen promotes weight loss, glycemic normalization and induces adaptations of ketogenic pathways in liver and kidney.

Objective: The ketogenic diet (KD), characterized by very limited dietary carbohydrate intake and used as nutritional treatment for GLUT1-deficiency syndromes and pharmacologically refractory epilepsy, may promote weight loss and improve metabolic fitness, potentially alleviating the symptoms of osteoarthritis. Here, we have studied the effects of administration of a ketogenic diet in mice previously rendered obese by feeding a high fat diet (HFD) and submitted to surgical destabilization of the medial meniscus to mimic osteoarthritis.

Methods: 6-weeks old mice were fed an HFD for 10 weeks and then switched to a chow diet (CD), KD or maintained on a HFD for 8 weeks.

Systematic review-pancreatic involvement in inflammatory bowel disease.

Background: Inflammatory bowel disease (IBD) is a chronic inflammatory immune-mediated disorder of the gut with frequent extra-intestinal complications. Pancreatic involvement in IBD is not uncommon and comprises a heterogeneous group of conditions, including acute pancreatitis (AP), chronic pancreatitis (CP), autoimmune pancreatitis (AIP) and pancreatic exocrine insufficiency (PEI); however, data on such an association remain sparse and heterogeneous.

Method: PubMed/MEDLINE and EMBASE databases were searched for studies investigating pancreatic involvement in patients with IBD.

Citrullination in the pathology of inflammatory and autoimmune disorders: recent advances and future perspectives.

Numerous post-translational modifications (PTMs) govern the collective metabolism of a cell through altering the structure and functions of proteins. The action of the most prevalent PTMs, encompassing phosphorylation, methylation, acylations, ubiquitination and glycosylation is well documented. A less explored protein PTM, conversion of peptidylarginine to citrulline, is the subject of this review.

Impact of COVID-19 on inflammatory bowel disease practice and perspectives for the future.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); since its first description in December 2019, it has rapidly spread to a global pandemic. Specific concerns have been raised concerning patients with inflammatory bowel diseases (IBD), which are chronic autoimmune inflammatory disorders of the gut that frequently require immunosuppressive and biological therapies to control their activity. Accumulating evidence has so far demonstrated that patients with IBD are not at increased risk of contracting severe acute respiratory syndrome coronavirus 2 infection.

Safety and clinical efficacy of the double switch from originator infliximab to biosimilars CT-P13 and SB2 in patients with inflammatory bowel diseases (SCESICS): A multicenter cohort study.

Data regarding double switching from originator infliximab (IFX) to IFX biosimilars in inflammatory bowel diseases (IBDs) are lacking. The purpose of this study was to evaluate the safety and efficacy of switching from originator IFX to CT-P13 and subsequently to SB2 (double switch) in patients with IBD. Patients undergoing IFX-double switch in eight Centers in Lombardy (Italy) from November 2018 to May 2019 were retrospectively analyzed.

Acute mesenteric ischemia and small bowel imaging findings in COVID-19: A comprehensive review of the literature.

Background: Coronavirus disease 2019 (COVID-19), an infectious condition caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread worldwide since its first description in Wuhan in December 2019. Even though respiratory manifestations are the most prevalent and responsible for disease morbidity and mortality, extrapulmonary involvement has progressively gained relevance. In particular, gastrointestinal (GI) signs and symptoms, reported in up to two-thirds of patients with COVID-19, might represent the first and, in some cases, the only disease presentation.

Effects of ketogenic diet and ketone bodies on the cardiovascular system: Concentration matters.

Ketone bodies have emerged as central mediators of metabolic health, and multiple beneficial effects of a ketogenic diet, impacting metabolism, neuronal pathologies and, to a certain extent, tumorigenesis, have been reported both in animal models and clinical research. Ketone bodies, endogenously produced by the liver, act pleiotropically as metabolic intermediates, signaling molecules, and epigenetic modifiers. The endothelium and the vascular system are central regulators of the organism's metabolic state and become dysfunctional in cardiovascular disease, atherosclerosis, and diabetic micro- and macrovascular complications.

Effects of maternal protein restriction on central and peripheral renin-angiotensin systems in male rat offspring.

Aims: We investigated the involvement of the renin angiotensin system (RAS) on the cardiorespiratory control in rats from dams fed with a low-protein diet.

Main Methods: Male offspring were obtained from dams fed a normoprotein diet (NP, 17% casein) and low-protein diet (LP, 8% casein) during pregnancy and lactation. Direct measurements of arterial pressure (AP), heart rate (HR) and respiratory frequency (RF) were recorded in awake 90-day-old at resting and after losartan potassium through either intracerebroventricular (ICV) microinjections or intravenous (IV) administration.

Effects of maternal low-protein diet and spontaneous physical activity on the transcription of neurotrophic factors in the placenta and the brains of mothers and offspring rats.

Maternal protein restriction and physical activity can affect the interaction mother-placenta-fetus. This study quantified the gene expression of brain-derived neurotrophic factor (BDNF), neurothrophin 4, tyrosine kinase receptor B (TrkB/NTRK2), insulin-like growth factor (IGF-1), and insulin-like growth factor receptor (IGF-1r) in the different areas of mother's brain (hypothalamus, hippocampus, and cortex), placenta, and fetus' brain of rats. Female Wistar rats (n = 20) were housed in cages containing a running wheel for 4 weeks before gestation.

Maternal low protein diet induces persistent expression changes in metabolic genes in male rats.

Background: Perinatal exposure to a poor nutritional environment predisposes the progeny to the development of metabolic disease at the adult age, both in experimental models and humans. Numerous adaptive responses to maternal protein restriction have been reported in metabolic tissues. However, the expression of glucose/fatty acid metabolism-related genes in adipose tissue and liver needs to be described.