Translational characterization of the temporal dynamics of metabolic dysfunctions in liver, adipose tissue and the gut during diet-induced NASH development in Ldlr-/-.Leiden mice

Background: NAFLD progression, from steatosis to inflammation and fibrosis, results from an interplay of intra- and extrahepatic mechanisms. Disease drivers likely include signals from white adipose tissue (WAT) and gut. However, the temporal dynamics of disease development remain poorly understood. Methods: High-fat-diet (HFD)-fed Ldlr-/-...

Intervention with isoleucine or valine corrects hyperinsulinemia and reduces intrahepatic diacylglycerols, liver steatosis, and inflammation in Ldlr-/-.Leiden mice with manifest obesity-associated NASH

Non-alcoholic steatohepatitis (NASH) is associated with a disturbed metabolism in liver, insulin resistance, and excessive accumulation of ectopic fat. Branched-chain amino acids (BCAAs) may beneficially modulate hepatic lipids, however, it remains unclear whether individual BCAAs can attenuate already established NASH and associated oxidative...

Heat-Inactivated Akkermansia muciniphila Improves Gut Permeability but Does Not Prevent Development of Non-Alcoholic Steatohepatitis in Diet-Induced Obese Ldlr-/-.Leiden Mice

The development of non-alcoholic steatohepatitis (NASH) has been associated with alterations in gut microbiota composition and reduced gut barrier function. Akkermansia muciniphila is a gut microbe that is thought to have health-promoting properties, including the ability to improve gut barrier function and host metabolism, both when...

Diffusion of charged and uncharged contrast agents in equine mandibular condylar cartilage is not affected by an increased level of sugar-induced collagen crosslinking

Nutrition of articular cartilage relies mainly on diffusion and convection of solutes through the interstitial fluid due to the lack of blood vessels. The diffusion is controlled by two factors: steric hindrance and electrostatic interactions between the solutes and the matrix components. Aging comes with changes in the cartilage structure and...

Mechanical stiffness of TMJ condylar cartilage increases after artificial aging by ribose

Objective: Aging is accompanied by a series of changes in mature tissues that influence their properties and functions. Collagen, as one of the main extracellular components of cartilage, becomes highly crosslinked during aging. In this study, the aim was to examine whether a correlation exists between collagen crosslinking induced by artificial...

Aging does not change the compressive stiffness of mandibular condylar cartilage in horses

Objective Aging can cause an increase in the stiffness of hyaline cartilage as a consequence of increased protein crosslinks. By induction of crosslinking, a reduction in the diffusion of solutions into the hyaline cartilage has been observed. However, there is a lack of knowledge about the effects of aging on the biophysical and biochemical...

Non-enzymatic cross-linking of collagen type II fibrils is tuned via osmolality switch

An important aspect in cartilage ageing is accumulation of advanced glycation end products (AGEs) after exposure to sugars. Advanced glycation results in cross-links formation between the collagen fibrils in articular cartilage, hampering their flexibility and making cartilage more brittle. In the current study, we investigate whether collagen...

Butyrate Reduces HFD-Induced Adipocyte Hypertrophy and Metabolic Risk Factors in Obese LDLr-/-.Leiden Mice

Adipose tissue (AT) has a modulating role in obesity-induced metabolic complications like type 2 diabetes mellitus (T2DM) via the production of so-called adipokines such as leptin, adiponectin, and resistin. The adipokines are believed to influence other tissues and to affect insulin resistance, liver function, and to increase the risk of T2DM....

Matrix cross-linking lysyl oxidases are induced in response to myocardial infarction and promote cardiac dysfunction

Aims After myocardial infarction (MI), extensive remodelling of the extracellular matrix contributes to scar formation. While aiming to preserve tissue integrity, this fibrotic response is also associated with adverse events, including a markedly increased risk of heart failure, ventricular arrhythmias, and sudden cardiac death. Cardiac fibrosis...