Key Inflammatory Processes in Human NASH Are Reflected in Ldlr-/-.Leiden Mice: A Translational Gene Profiling Study

Introduction: It is generally accepted that metabolic inflammation in the liver is an important driver of disease progression in NASH and associated matrix remodeling/fibrosis. However, the exact molecular inflammatory mechanisms are poorly defined in human studies. Investigation of key pathogenic mechanisms requires the use of pre-clinical...

Uncovering a Predictive Molecular Signature for the Onset of NASH-Related Fibrosis in a Translational NASH Mouse Model

Background & Aims: The incidence of nonalcoholic steatohepatitis (NASH) is increasing. The pathophysiological mechanisms of NASH and the sequence of events leading to hepatic fibrosis are incompletely understood. The aim of this study was to gain insight into the dynamics of key molecular processes involved in NASH and to rank early markers for...

CAT-2003: A Novel Sterol Regulatory Element-Binding Protein Inhibitor That Reduces Steatohepatitis, Plasma Lipids, and Atherosclerosis in Apolipoprotein E*3-Leiden Mice

CAT-2003 is a novel conjugate of eicosapentaenoic acid (EPA) and niacin designed to be hydrolyzed by fatty acid amide hydrolase to release EPA inside cells at the endoplasmic reticulum. In cultured liver cells, CAT-2003 blocked the maturation of sterol regulatory element-binding protein (SREBP)-1 and SREBP-2 proteins and decreased the expression...

Protective effect of rosiglitazone on kidney function in high-fat challenged human-CRP transgenic mice: a possible role for adiponectin and miR-21?

Obesity-related albuminuria is associated with decline of kidney function and is considered a first sign of diabetic nephropathy. Suggested factors linking obesity to kidney dysfunction include low-grade inflammation, insulin resistance and adipokine dysregulation. Here, we investigated the effects of two pharmacological compounds with...

A casein hydrolysate based formulation attenuates obesity and associated non-alcoholic fatty liver disease and atherosclerosis in LDLr-/-.Leiden mice

Background: Obesity frequently associates with the development of non-alcoholic fatty liver disease (NAFLD) and atherosclerosis. Chronic inflammation in white adipose tissue (WAT) seems to be an important driver of these manifestations. Objective: This study investigated a combination of an extensively hydrolyzed casein (eHC), docosahexaenoic...

Resolvin E1 attenuates atherosclerosis in absence of cholesterol-lowering effects and on top of atorvastatin

Background and aims Besides LDL-cholesterol, local vascular inflammation plays a key role in atherogenesis. Efficient therapies to treat the inflammatory component of the disease have not been established. The discovery of specialized inflammation-resolving mediators, such as resolvins may provide new opportunities for treatment. This study...

Orthopedic surgery increases atherosclerotic lesions and necrotic core area in ApoE−/− mice

Background and aims Observational studies show a peak incidence of cardiovascular events after major surgery. For example, the risk of myocardial infarction increases 25-fold early after hip replacement. The acuteness of this increased risk suggests abrupt enhancement in plaque vulnerability, which may be related to intra-plaque inflammation,...

Metabolic inflammation in hepatic and vascular disorders: Strategies to attenuate disease development [Metabole ziekten voorkomen door gezonder te eten]

Over the past few decades it has become increasingly clear that inflammation – a normal and essential defense mechanism that protects the body from infection and injury – can also be triggered by nutrients and dietary surplus, an inflammatory state that is referred to as metabolic inflammation. This chronic low-grade inflammatory state is...

Reduction of obesity-associated white adipose tissue inflammation by rosiglitazone is associated with reduced non-alcoholic fatty liver disease in LDLr-deficient mice

Obesity is associated with chronic low-grade inflammation that drives the development of metabolic diseases, including non-alcoholic fatty liver disease (NAFLD). We recently showed that white adipose tissue (WAT) constitutes an important source of inflammatory factors. Hence, interventions that attenuate WAT inflammation may reduce NAFLD...

Effects of anthocyanin and flavanol compunds on lipid metabolism and adipose tissue associated systemic inflammation in diet-induced obesity

Background. Naturally occurring substances from the flavanol and anthocyanin family of polyphenols have been proposed to exert beneficial effects in the course of obesity. We hypothesized that their effects on attenuating obesity-induced dyslipidemia as well as the associated inflammatory sequelae especially have health-promoting potential....

Intervention with a caspase-1 inhibitor reduces obesity-associated hyperinsulinemia, non-alcoholic steatohepatitis (NASH) and hepatic fibrosis in LDLR-/-.Leiden mice

Background/objectives: Non-alcoholic steatohepatitis (NASH) is a serious liver condition, closely associated with obesity and insulin resistance. Recent studies have suggested an important role for inflammasome/caspase-1 in the development of NASH, but the potential therapeutic value of caspase-1 inhibition remains unclear. Therefore, we aimed...

Surgical removal of inflamed epididymal white adipose tissue attenuates the development of non-alcoholic steatohepatitis in obesity

Background: Non-alcoholic fatty liver disease (NAFLD) is strongly associated with abdominal obesity. Growing evidence suggests that inflammation in specific depots of white adipose tissue (WAT) has a key role in NAFLD progression, but experimental evidence for a causal role of WAT is lacking. Methods: A time-course study in C57BL/6J mice was...

High-fat diet induced obesity primes inflammation in adipose tissues prior to liver in C57BL/6j mice

Metabolic inflammation in adipose tissue and the liver is frequently observed as a result of diet-induced obesity in human and rodent studies. Although the adipose tissue and the liver are both prone to become chronically inflamed with prolonged obesity, their individual contribution to the development of metabolic inflammation remains...

Mirtoselect, an anthocyanin-rich bilberry extract, attenuates non-alcoholic steatohepatitis and associated fibrosis in ApoE∗3Leiden mice

Background & Aims Anthocyanins may have beneficial effects on lipid metabolism and inflammation and are demonstrated to have hepatoprotective properties in models of restraint-stress- and chemically-induced liver damage. However, their potential to protect against non-alcoholic steatohepatitis (NASH) under conditions relevant for human...

Role of Macrophage Migration Inhibitory Factor in Obesity, Insulin Resistance, Type 2 Diabetes, and Associated Hepatic Co-Morbidities: A Comprehensive Review of Human and Rodent Studies

Obesity is associated with a chronic low-grade inflammatory state that drives the -development of obesity-related co-morbidities such as insulin resistance/type 2 diabetes, non-alcoholic fatty liver disease (NAFLD), and cardiovascular disease. This metabolic inflammation is thought to originate in the adipose tissue, which becomes inflamed and...