Identifying the location-dependent adipose tissue bacterial DNA signatures in obese patients that predict body weight loss.

Recent sets of evidence have described profiles of 16S rDNA sequences in host tissues, notably in fat pads that are significantly overrepresented and can serve as signatures of metabolic disease. However, these recent and original observations need to be further detailed and functionally defined. Here, using state-of-the-art targeted DNA sequencing and discriminant predictive approaches, we describe, from the longitudinal FLORINASH cohort of patients who underwent bariatric surgery, visceral, and subcutaneous fat pad-specific bacterial 16SrRNA signatures.

Iatrogenic cerebral amyloid angiopathy: Two case reports to explore clinical heterogeneity and pathological patterns.

Introduction: These case reports illustrate Iatrogenic Cerebral Amyloid Angiopathy (iCAA) due to neurosurgical procedures. Recent studies propose prion transmission during neurosurgery as a potential mechanism for β-amyloid seed implantation, linking neurosurgical history to the development of iCAA. The majority of reported cases in the literature have an unfavorable prognosis, with recurrence of intracerebral hemorrahge (ICH) and subsequent death during the first months of follow-up.

The visceral adipose tissue bacterial microbiota provides a signature of obesity based on inferred metagenomic functions.

Background: Metabolic inflammation mediated obesity requires bacterial molecules to trigger immune and adipose cells leading to inflammation and adipose depot development. In addition to the well-established gut microbiota dysbiosis, a leaky gut has been identified in patients with obesity and animal models, characterized by the presence of a tissue microbiota in the adipose fat pads.

Methods: To determine its potential role, we sequenced the bacterial 16 S rRNA genes in the visceral adipose depot of patients with obesity.

Dysbiosis: An Indicator of COVID-19 Severity in Critically Ill Patients.

Here, we examined the dynamics of the gut and respiratory microbiomes in severe COVID-19 patients in need of mechanical ventilation in the intensive care unit (ICU). We recruited 85 critically ill patients (53 with COVID-19 and 32 without COVID-19) and 17 healthy controls (HCs) and monitored them for up to 4 weeks. We analyzed the bacterial and fungal taxonomic profiles and loads of 232 gut and respiratory samples and we measured the blood levels of Interleukin 6, IgG, and IgM in COVID-19 patients.

Downregulation of peripheral lipopolysaccharide binding protein impacts on perigonadal adipose tissue only in female mice.

Background And Aims: The sexual dimorphism in fat-mass distribution and circulating leptin and insulin levels is well known, influencing the progression of obesity-associated metabolic disease. Here, we aimed to investigate the possible role of lipopolysaccharide-binding protein (LBP) in this sexual dimorphism.

Methods: The relationship between plasma LBP and fat mass was evaluated in 145 subjects.

Dysregulation of macrophage PEPD in obesity determines adipose tissue fibro-inflammation and insulin resistance.

Resulting from impaired collagen turnover, fibrosis is a hallmark of adipose tissue (AT) dysfunction and obesity-associated insulin resistance (IR). Prolidase, also known as peptidase D (PEPD), plays a vital role in collagen turnover by degrading proline-containing dipeptides but its specific functional relevance in AT is unknown. Here we show that in human and mouse obesity, PEPD expression and activity decrease in AT, and PEPD is released into the systemic circulation, which promotes fibrosis and AT IR.

ITCH E3 ubiquitin ligase downregulation compromises hepatic degradation of branched-chain amino acids.

Metabolic syndrome, obesity, and steatosis are characterized by a range of dysregulations including defects in ubiquitin ligase tagging proteins for degradation. The identification of novel hepatic genes associated with fatty liver disease and metabolic dysregulation may be relevant to unravelling new mechanisms involved in liver disease progression METHODS: Through integrative analysis of liver transcriptomic and metabolomic obtained from obese subjects with steatosis, we identified itchy E ubiquitin protein ligase (ITCH) as a gene downregulated in human hepatic tissue in relation to steatosis grade. Wild-type or ITCH knockout mouse models of non-alcoholic fatty liver disease (NAFLD) and obesity-related hepatocellular carcinoma were analyzed to dissect the causal role of ITCH in steatosis RESULTS: We show that ITCH regulation of branched-chain amino acids (BCAAs) degradation enzymes is impaired in obese women with grade 3 compared with grade 0 steatosis, and that ITCH acts as a gatekeeper whose loss results in elevation of circulating BCAAs associated with hepatic steatosis.

Transdiagnostic Perspective of Impulsivity and Compulsivity in Obesity: From Cognitive Profile to Self-Reported Dimensions in Clinical Samples with and without Diabetes.

Impulsive and compulsive behaviors have both been observed in individuals with obesity. The co-occurrence of obesity and type 2 diabetes (T2D) is more strongly associated with impulsivity, although there are no conclusive results yet. A multidimensional assessment of impulsivity and compulsivity was conducted in individuals with obesity in the absence or presence of T2D, compared with healthy, normal-weight individuals, with highly impulsive patients (gambling disorders), and with highly compulsive patients (anorexia nervosa).

BMP8 and activated brown adipose tissue in human newborns.

The classical dogma states that brown adipose tissue (BAT) plays a major role in the regulation of temperature in neonates. However, although BAT has been studied in infants for more than a century, the knowledge about its physiological features at this stage of life is rather limited. This has been mainly due to the lack of appropriate investigation methods, ethically suitable for neonates.

Novel Relationship Between Plasmalogen Lipid Signatures and Carnosine in Humans.

Introduction: Carnosine is a naturally occurring dipeptide abundant in the skeletal and cardiac muscle and brain, which has been shown to improve glucose metabolism and cardiovascular risk. This study showed that carnosine supplementation had positive changes on plasma lipidome. Here, this study aimed to establish the relationship of muscle carnosine and serum carnosinase-1 with cardiometabolic risk factors and the lipidome.

Cecal Ligation and Puncture-Induced Sepsis Promotes Brown Adipose Tissue Inflammation Without Any Impact on Expression of Thermogenic-Related Genes.

The negative effects of chronic low-level inflammation on adipose tissue physiology have been extensively demonstrated, whereas the effects of acute inflammation are less studied. Here, we aimed to investigate the effects of sepsis-induced acute inflammation on gene expression markers of brown and white adipose tissue functionality. Brown adipose tissue (BAT) and perirenal white adipose tissue (prWAT) gene expression markers were analyzed in cecal ligation and puncture (CLP)-induced sepsis mice model.

Iron status influences non-alcoholic fatty liver disease in obesity through the gut microbiome.

Background: The gut microbiome and iron status are known to play a role in the pathophysiology of non-alcoholic fatty liver disease (NAFLD), although their complex interaction remains unclear.

Results: Here, we applied an integrative systems medicine approach (faecal metagenomics, plasma and urine metabolomics, hepatic transcriptomics) in 2 well-characterised human cohorts of subjects with obesity (discovery n = 49 and validation n = 628) and an independent cohort formed by both individuals with and without obesity (n = 130), combined with in vitro and animal models. Serum ferritin levels, as a markers of liver iron stores, were positively associated with liver fat accumulation in parallel with lower gut microbial gene richness, composition and functionality.

Adipose tissue knockdown of lysozyme reduces local inflammation and improves adipogenesis in high-fat diet-fed mice.

Chronic systemic low-level inflammation in metabolic disease is known to affect adipose tissue biology. Lysozyme (LYZ) is a major innate immune protein but its role in adipose tissue has not been investigated. Here, we aimed to investigate LYZ in human and rodents fat depots, and its possible role in obesity-associated adipose tissue dysfunction.

Arrhythmogenic substrate detection in chronic ischaemic patients undergoing ventricular tachycardia ablation using multidetector cardiac computed tomography: compared evaluation with cardiac magnetic resonance.

Aims: Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) permits characterizing ischaemic scars, detecting heterogeneous tissue channels (HTCs) which constitute the arrhythmogenic substrate (AS). Late gadolinium enhancement cardiac magnetic resonance also improves the arrhythmia-free survival when used to guide ventricular tachycardia (VT) substrate ablation. However, its availability may be limited.

Nicotine' actions on energy balance: Friend or foe?

Obesity has reached pandemic proportions and is associated with severe comorbidities, such as type 2 diabetes mellitus, hepatic and cardiovascular diseases, and certain cancer types. However, the therapeutic options to treat obesity are limited. Extensive epidemiological studies have shown a strong relationship between smoking and body weight, with non-smokers weighing more than smokers at any age.

Lysozyme is a component of the innate immune system linked to obesity associated-chronic low-grade inflammation and altered glucose tolerance.

Background & Aims: Several proteins of the innate immune system are known to be deregulated with insulin resistance. We here aimed to investigate the relationship among circulating lysozyme (both plasma concentration and activity) and obesity-associated metabolic disturbances.

Methods: Plasma lysozyme concentration was determined cross-sectionally in a discovery (Cohort 1, n = 137) and in a replication cohort (Cohort 2, n = 181), in which plasma lysozyme activity was also analyzed.

Molecular phenomics of a high-calorie diet-induced porcine model of prepubertal obesity.

As obesity incidence is alarmingly rising among young individuals, we aimed to characterize an experimental model of this situation, considering the similarity between human and porcine physiology. For this reason, we fed prepubertal (63 days old) Duroc breed females (n=21) either with a standard growth diet (3800 kcal/day) or one with a high-calorie content (5200 kcal/day) during 70 days. Computerized tomography, mass-spectrometry-based metabolomics and lipidomics, as well as peripheral blood mononuclear cell transcriptomics, were applied to define traits linked to high-calorie intake.

Low AMY1 Copy Number Is Cross-Sectionally Associated to an Inflammation-Related Lipidomics Signature in Overweight and Obese Individuals.

Scope: Reduced amylase 1 (AMY1) copy numbers are associated with obesity, insulin resistance, and inflammation. Although mechanisms linking AMY1 copy number with metabolic disorders are poorly understood, recent findings suggest that lipids play a key role.

Methods And Results: Plasma lipidomic signatures associated with AMY1 copy number are explored in 57 non-diabetic overweight/obese subjects aged 18-60.

The APOA1bp-SREBF-NOTCH axis is associated with reduced atherosclerosis risk in morbidly obese patients.

Background & Aims: Atherosclerosis is characterized by an inflammatory disease linked to excessive lipid accumulation in the artery wall. The Notch signalling pathway has been shown to play a key regulatory role in the regulation of inflammation. Recently, in vitro and pre-clinical studies have shown that apolipoprotein A-I binding protein (AIBP) regulates cholesterol metabolism (SREBP) and NOTCH signalling (haematopoiesis) and may be protective against atherosclerosis, but the evidence in humans is scarce.

Compounds that modulate AMPK activity and hepatic steatosis impact the biosynthesis of microRNAs required to maintain lipid homeostasis in hepatocytes.

Background: While the impact of metformin in hepatocytes leads to fatty acid (FA) oxidation and decreased lipogenesis, hepatic microRNAs (miRNAs) have been associated with fat overload and impaired metabolism, contributing to the pathogenesis of non-alcoholic fatty liver disease (NAFLD).

Methods: We investigated the expression of hundreds of miRNAs in primary hepatocytes challenged by compounds modulating steatosis, palmitic acid and compound C (as inducers), and metformin (as an inhibitor). Then, additional hepatocyte and rodent models were evaluated, together with transient mimic miRNAs transfection, lipid droplet staining, thin-layer chromatography, quantitative lipidomes, and mitochondrial activity, while human samples outlined the translational significance of this work.

Plasma Phospholipids with Long-Chain Polyunsaturated Fatty Acids and Dihydroceramides at the Crossroads of Iron Stores and Insulin Resistance.

Scope: Iron plays an important role in the pathogenesis of insulin resistance (IR) and type 2 diabetes. Recent studies suggest a role of specific lipids in the induction of IR, but the potential relationships between iron and lipid metabolites in relation to IR have not been explored. Therefore, the aim of the study is to evaluate the association among iron, IR, and the lipidome.