Osteopontin-driven T-cell accumulation and function in adipose tissue and liver promoted insulin resistance and MAFLD.

Objective: This study investigated the contribution of osteopontin/secreted phosphoprotein 1 (SPP1) to T-cell regulation in initiation of obesity-driven adipose tissue (AT) inflammation and macrophage infiltration and the subsequent impact on insulin resistance (IR) and metabolic-associated fatty liver disease (MAFLD) development.

Methods: SPP1 and T-cell marker expression was evaluated in AT and liver according to type 2 diabetes and MAFLD in human individuals with obesity. The role of SPP1 on T cells was evaluated in Spp1-knockout mice challenged with a high-fat diet.

Arterial Calcifications in Patients with Liver Cirrhosis Are Linked to Hepatic Deficiency of Pyrophosphate Production Restored by Liver Transplantation.

Liver fibrosis is associated with arterial calcification (AC). Since the liver is a source of inorganic pyrophosphate (PPi), an anti-calcifying compound, we investigated the relationship between plasma PPi ([PPi]pl), liver fibrosis, liver function, AC, and the hepatic expression of genes regulating PPi homeostasis. To that aim, we compared [PPi]pl before liver transplantation (LT) and 3 months after LT.

Endoplasmic reticulum-mitochondria miscommunication is an early and causal trigger of hepatic insulin resistance and steatosis.

Background & Aims: Hepatic insulin resistance in obesity and type 2 diabetes was recently associated with endoplasmic reticulum (ER)-mitochondria miscommunication. These contact sites (mitochondria-associated membranes: MAMs) are highly dynamic and involved in many functions; however, whether MAM dysfunction plays a causal role in hepatic insulin resistance and steatosis is not clear. Thus, we aimed to determine whether and how organelle miscommunication plays a role in the onset and progression of hepatic metabolic impairment.

SYK-3BP2 Pathway Activity in Parenchymal and Myeloid Cells Is a Key Pathogenic Factor in Metabolic Steatohepatitis.

Background & Aims: Spleen tyrosine kinase (SYK) signaling pathway regulates critical processes in innate immunity, but its role in parenchymal cells remains elusive in chronic liver diseases. We investigate the relative contribution of SYK and its substrate c-Abl Src homology 3 domain-binding protein-2 (3BP2) in both myeloid cells and hepatocytes in the onset of metabolic steatohepatitis.

Methods: Hepatic SYK-3BP2 pathway was evaluated in mouse models of metabolic-associated fatty liver diseases (MAFLD) and in obese patients with biopsy-proven MAFLD (n = 33).

Prevalence of NASH/NAFLD in people with obesity who are currently classified as metabolically healthy.

Background: While metabolic health in obesity may confer a protective status, recent studies indicate that nonalcoholic fatty liver disease (NAFLD) or even nonalcoholic steatohepatitis (NASH) may exist in this category of individuals. Although cardiovascular and diabetic risks have been well described, the risk of NAFLD and NASH among this population requires further investigation.

Objective: Our goal was to compare the prevalence of steatosis, NAFLD, and NASH between individuals with metabolically healthy obesity (MHO) and individuals with metabolically abnormal obesity (MAO) and to identify preoperative risk factors for these conditions in a prospective cohort with morbid obesity scheduled for bariatric surgery.

MCD diet-induced steatohepatitis generates a diurnal rhythm of associated biomarkers and worsens liver injury in Klf10 deficient mice.

A large number of hepatic functions are regulated by the circadian clock and recent evidence suggests that clock disruption could be a risk factor for liver complications. The circadian transcription factor Krüppel like factor 10 (KLF10) has been involved in liver metabolism as well as cellular inflammatory and death pathways. Here, we show that hepatic steatosis and inflammation display diurnal rhythmicity in mice developing steatohepatitis upon feeding with a methionine and choline deficient diet (MCDD).

Accurate assessment of nonalcoholic fatty liver disease lesions in liver allograft biopsies by a smartphone platform: A proof of concept.

Macrovesicular steatosis (MS) is a major risk factor for liver graft failure after transplantation and pathological microscopic examination of a frozen tissue section remains the gold standard for its assessment. However, the latter requires an experienced in-house pathologist for correct and rapid diagnosis as well as specific equipment that is not always available. Smartphones, which are must-have tools for everyone, are very suitable for incorporation into promising technology to generate moveable diagnostic tools as for telepathology.

REDD1 deficiency protects against nonalcoholic hepatic steatosis induced by high-fat diet.

Nonalcoholic fatty liver disease is a chronic liver disease which is associated with obesity and insulin resistance. We investigated the implication of REDD1 (Regulated in development and DNA damage response-1), a stress-induced protein in the development of hepatic steatosis. REDD1 expression was increased in the liver of obese mice and morbidly obese patients, and its expression correlated with hepatic steatosis and insulin resistance in obese patients.

The mid-infrared spectroscopy: A novel non-invasive diagnostic tool for NASH diagnosis in severe obesity.

Unlabelled: There is an urgent medical need to develop non-invasive tests for non-alcoholic steatohepatitis (NASH). This study evaluates the diagnostic performance of an innovative model based on mid-infrared (MIR) spectroscopy for the diagnosis of NASH.

Methods: Severely obese patients who underwent a bariatric procedure at the University Hospital of Nice, France (n = 395) were prospectively recruited.

Hepatic FNDC5 is a potential local protective factor against Non-Alcoholic Fatty Liver.

The proteolytic cleavage of Fibronectin type III domain-containing 5 (FNDC5) generates soluble irisin. Initially described as being mainly produced in muscle during physical exercise, irisin mediates adipose tissue thermogenesis and also regulates carbohydrate and lipid metabolism. The aim of this study was to evaluate the hepatic expression of FNDC5 and its role in hepatocytes in Non-Alcoholic Fatty Liver (NAFL).

The Differential Expression of Cide Family Members is Associated with Nafld Progression from Steatosis to Steatohepatitis.

Improved understanding of the molecular mechanisms responsible for the progression from a "non-pathogenic" steatotic state to Non-Alcoholic Steatohepatitis is an important clinical requirement. The cell death-inducing DFF45 like effector (CIDE) family members (A, B and FSP27) regulate hepatic lipid homeostasis by controlling lipid droplet growth and/or VLDL production. However, CIDE proteins, particularly FSP27, have a dual role in that they also regulate cell death.

Bax inhibitor-1 protects from nonalcoholic steatohepatitis by limiting inositol-requiring enzyme 1 alpha signaling in mice.

Unlabelled: Endoplasmic reticulum (ER) stress is activated in nonalcoholic fatty liver disease (NAFLD), raising the possibility that ER stress-dependent metabolic dysfunction, inflammation, and cell death underlie the transition from steatosis to steatohepatitis (nonalcoholic steatohepatitis; NASH). B-cell lymphoma 2 (BCL2)-associated X protein (Bax) inhibitor-1 (BI-1), a negative regulator of the ER stress sensor, inositol-requiring enzyme 1 alpha (IRE1α), has yet to be explored in NAFLD as a hepatoprotective agent. We hypothesized that the genetic ablation of BI-1 would render the liver vulnerable to NASH because of unrestrained IRE1α signaling.

Non-invasive Evaluation of NAFLD with Indocyanine Green Clearance Test: a Preliminary Study in Morbidly Obese Patients Undergoing Bariatric Surgery.

Background: Overweight and obesity dramatically increased in the last years. Hepatic complication of obesity, integrated in the term of non-alcoholic fatty liver disease (NAFLD), is a spectrum of abnormality ranging from steatosis to non-alcoholic steatohepatitis (NASH), potentially leading to cirrhosis. Liver biopsy remains the gold standard to evaluate the stage of NAFLD; however, the procedure is invasive.

CD44 is a key player in non-alcoholic steatohepatitis.

Background & Aims: Cluster of differentiation (CD)44 regulates adipose tissue inflammation in obesity and hepatic leukocyte recruitment in a lithogenic context. However, its role in hepatic inflammation in a mouse model of steatohepatitis and its relevance in humans have not yet been investigated. We aimed to evaluated the contribution of CD44 to non-alcoholic steatohepatitis (NASH) development and liver injury in mouse models and in patients at various stages of non-alcoholic fatty liver disease (NAFLD) progression.

Roux-En Y Gastric Bypass Results in Long-Term Remission of Hepatocyte Apoptosis and Hepatic Histological Features of Non-alcoholic Steatohepatitis.

The long-term effects of bariatric surgery on non-alcoholic steatohepatitis (NASH), focusing on liver injury and hepatocyte apoptosis, are not well-established. We here performed a longitudinal study with paired liver biopsies of nine morbidly obese women (median BMI: 42 [38.7; 45.

Study of LAT1 Expression in Brain Metastases: Towards a Better Understanding of the Results of Positron Emission Tomography Using Amino Acid Tracers.

Positron emission tomography using radiolabeled amino acid (PET-AA) appears to be promising in distinguishing between recurrent tumour and radionecrosis in the follow-up of brain metastasis (BM). The amino acid transporter LAT1 and its cofactor CD98, which are involved in AA uptake, have never been investigated in BM. The aim of our study was to determine and compare the expression of LAT1 and CD98 in BM and in non-tumoral brain tissue (NT).

Acquired Localized (Monodactylous) Longitudinal Pachyonychia and Onychocytic Carcinoma In Situ (2 Cases): Part II.

The authors have recently proposed to use the name pachyonychia as an umbrella term that includes 2 distinctly different entities in the form of congenital pachyonychia and acquired longitudinal pachyonychia. Congenital pachyonychia is defined by a diffuse hyperkeratosis of the nail bed. Acquired longitudinal pachyonychia correspond to the true definition of pachyonychia, that is, a thickened nail plate without subungual keratosis.

Immunoglobulin G4-associated autoimmune hepatitis may be found in Western countries.

Background: Immunoglobulin G4-related disease is a multi-systemic autoimmune disease. The sole involvement of the liver has been recently reported in Japanese patients and named "immunoglobulin G4-associated autoimmune hepatitis".

Aim: To examine the baseline and the 2-year follow-up characteristics of non-Asian patients with immunoglobulin G4-associated autoimmune hepatitis compared to patients with classical autoimmune hepatitis.

Severe Vitamin D Deficiency May be an Additional Cofactor for the Occurrence of Alcoholic Steatohepatitis.

Background: Among its pleiotropic effects, vitamin D may protect the liver from fibrosis and/or inflammation. However, the impact of vitamin D on liver pathology in hepatitis C remains unclear, and very few studies including alcoholic patients with liver pathologies have been performed. Here we compared the levels of 25-OH vitamin D in the blood of alcoholic patients with the occurrence of alcoholic steatohepatitis (ASH) or bridging fibrosis.

Maternal protein restriction leads to pancreatic failure in offspring: role of misexpressed microRNA-375.

The intrauterine environment of the fetus is a preeminent actor in long-term health. Indeed, mounting evidence shows that maternal malnutrition increases the risk of type 2 diabetes (T2D) in progeny. Although the consequences of a disturbed prenatal environment on the development of the pancreas are known, the underlying mechanisms are poorly defined.