Inflammation INSIGHTS

Obesity causes metabolic dysfunctions that lead to debilitating chronic diseases including type 2 diabetes, fatty liver disease, and cirrhosis. Diet-induced obese (DIO) rodents are popular models for studying obesity and pre-diabetes. In 1953, Fenton and Dowling manipulated nutrient composition across a range of refined rodent diets, demonstrating that inbred weanling mice could be induced to obesity on an accelerated timeline1. Since then, DIO mice have become staples...  Read More

Numerous strains of mice will develop obesity, nonalcoholic fatty liver disease (NAFLD), and nonalcoholic steatohepatitis (NASH) when fed a "Western" diet enriched in saturated or trans fats, cholesterol, glucose, and fructose. This triggers weight gain, hepatic steatosis, and lipotoxic inflammation, leading to liver fibrosis and dysfunction. In many ways this mimics the etiology and progression of the spectrum of human disease. Obesity and its resulting comorbidities largely...  Read More

Bile acids (BAs) are small detergent molecules that are primarily known for their ability to promote intestinal lipid absorption. While their primary function is associated with gut metabolism, they also are key players in other physiological signaling pathways related to microbiome maintenance, the regulation of glucose, lipid, and energy homeostasis, and cellular immunity. One of the fundamental areas of investigation in BA metabolism is how BA mechanisms...  Read More

Changing diets and lifestyles across much of the world contribute to a wide range of diseases and health conditions, including heart disease, hypertension, and type 2 diabetes. Another looming health crisis related to lifestyle is now on the horizon: a surge in the incidence of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), a more severe form of NAFLD. As researchers aim to unravel this complex...  Read More

Mdr1a knockout mice are becoming a more frequently utilized colitis model in IBD research due to their translational relevance, microbiome-driven chronic phenotype of colitis, and presence of a functional immune system. However, the primary mechanisms by which colitis appears in the Mdr1a KO mouse are not fully understood. MDR1 is a drug and xenobiotic efflux pump with substrates ranging from steroids to glycolipids1. There are two genetic...  Read More

Over 100 scientists joined Taconic Biosciences for the virtual workshop on "IBD Mouse Modeling - Best Practices for Drug Discovery and Emerging Models". The more than 3-hour event covered a variety of topics, including variability and reproducibility of the models and their use for target discovery and therapeutic efficacy. Prior to the event, many attendees submitted questions surrounding some of the challenges they have encountered with their...  Read More

Janus kinase (JAK) inhibitors are a promising recent addition to the inflammatory bowel disease (IBD) armamentarium. Tofacitinib, a small molecule pan-JAK inhibitor, received FDA approval in 2018 for the treatment of adult patients with moderate-to-severe ulcerative colitis1. Tofacitinib is non-selective and inhibits all four JAK isoforms (JAK1, JAK2, JAK3, TYK2), and research is currently underway to determine if isoform- or tissue-specific JAK inhibition could offer better efficacy...  Read More

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

Dr. Philip Dubé of Taconic Biosciences presented a recent webinar on genetically engineered models (GEMs) of colitis, which are widely used for preclinical research on inflammatory bowel disease (IBD). Although a wide array of GEM colitis models exist, Dr. Dubé focused on a few models which are both most commonly used and most useful for drug discovery. He discussed the relevance of the disease mechanism in each...  Read More

Nonalcoholic steatohepatitis, also known as NASH, is categorized by liver inflammation and fibrosis due to a buildup of fat in the liver. It represents a more severe form of nonalcoholic fatty liver disease (NAFLD), which currently has no approved pharmaceutical treatment. There are various types of mouse models used to study NASH, including diet-induced (both high fat and nutrient-deficient diets), chemically-induced, and genetic models. Of these, high...  Read More