Metabolic Disease INSIGHTS

Numerous diet-based models have been developed to induce nonalcoholic fatty liver disease and steatohepatitis (NAFLD/NASH) in mice. Chronic consumption of high-energy feeds enriched with fat causes steatotic buildup, lipotoxic inflammation, hepatic dysfunction, and liver fibrosis. Next generation diets1 include fructose and cholesterol as accelerants toward the diseased liver state. A key challenge to using diet-induced NASH mice for preclinical research involves selection and quantification of disease endpoints....  Read More

The Diet Induced NASH B6 displays hepatic crown-like structures, which are a unique histopathological characteristic seen in human livers with NASH. These hepatic crown-like structures are macrophages surrounding hepatocytes with large lipid vacuoles (blue arrows). Macrophages also form inflammatory cell aggregates with other leukocytes (red arrows). 20x magnification, F4/80 IHC on the liver from a C57BL/6NTac male mouse on NASH diet for 27 weeks. Dr. Cynthia Besch-Williford...  Read More

International Liver Congress™ 2019 Statistics. Source: EASL Nonalcoholic steatohepatitis (NASH) continues to be a hot topic in metabolic disease research. The NASH research field gathers twice a year at major conferences: The Liver Meeting is organized by the American Association for the Study of Liver Diseases (AASLD) in the US in the Autumn. International Liver Congress is organized by the European Association for the Study of the...  Read More

Stephanie Oldham and Christian Rivera of AstraZeneca recently presented a webinar on the use of a survivable liver biopsy in NASH mouse models, which is a technique that can provide valuable information on disease stage in individual mice prior to study initiation. In particular, it can be used to exclude outliers and properly randomize the remaining mice into study groups. Due to time constraints, many of the...  Read More

A wide variety of high fat diet-induced non-alcoholic steatohepatitis (NASH) models have been used to recapitulate certain etiological aspects of the disease, with refinements in dietary formulations made over the past decade. Amylin liver NASH model The Amylin liver NASH (AMLN) model was described by Trevaskis et al. in 2012 as a diet-induced model which displayed both aspects of NASH (nonalcoholic steatohepatitis) and metabolic syndrome. The authors...  Read More

Vitamins are organic molecules that are essential for proper metabolism and bodily function. While they go by different names, most vitamins are actually groups of chemically-related organic molecules known as vitamers1. Some vitamins must be obtained from dietary sources as they are produced in insufficient quantities or are not synthesized by the body at all. Humans have thirteen essential vitamins that must be obtained from dietary sources:...  Read More

Dr. Janell Richardson recently presented a webinar on the Diet Induced NASH B6, a translational model of NASH for drug discovery. She provided an excellent introduction to the global health problem of nonalcoholic steatohepatitis (NASH), gave an overview of different types of preclinical NASH models and focused in on the Diet Induced NASH B6 as a relevant model of NASH in the context of a metabolic disease...  Read More

The second annual International NASH Day took place on June 12, 2019. This day of action was launched last year to bring awareness to the global epidemic of NASH (nonalcoholic steatohepatitis). A coalition of worldwide organizations supported this effort including the American Liver Foundation, the Global Liver Institute and the NASH Education Program. According to a press release from the American Liver Foundation, "Millions of Americans are...  Read More

Inside each cell exist many complex smaller structures known as organelles. These micrometer-sized structures work to maintain intracellular transport, signaling, energy production, protein translation, DNA replication, and other essential cellular processes. One organelle which differs distinctly from others is the mitochondrion. In addition to generating the cell's energy in the form of adenosine triphosphate (ATP), mitochondria have their own DNA and replicate by binary fission. Mitochondrial DNA...  Read More

Oxidative stress is defined as "a disturbance in the balance between the production of reactive oxygen species (free radicals) and antioxidant defenses1". Long term oxidative stress on cells has been shown to be a key promoter of the development of disease; particularly cancer, diabetes, atherosclerosis, neurodegenerative disorders, hypertension, stroke, and arthritis2. Oxidative Stress and Cancer Risk Many cellular processes are negatively affected by increased oxidative stress, one,...  Read More