Inflammation INSIGHTS

The Classic Diet-Induced Obese Mouse Model is Still Enabling Breakthroughs in Drug Discovery for Metabolic Diseases

photo from The Classic Diet-Induced Obese Mouse Model is Still Enabling Breakthroughs in Drug Discovery for Metabolic Diseases

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

Thermoneutrality and Preclinical Modeling of Non-Alcoholic Fatty Liver Disease

photo from Thermoneutrality and Preclinical Modeling of Non-Alcoholic Fatty Liver Disease

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

Utility of Diet Induced Rodent Models to Investigate Dysregulation of Bile Acids in NASH

photo from Utility of Diet Induced Rodent Models to Investigate Dysregulation of Bile Acids in NASH

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

Modeling the Complex Disorder of NASH

photo from Modeling the Complex Disorder of NASH

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

Novel Molecular Mechanisms of Colitis in the Mdr1a KO Mouse

photo from Novel Molecular Mechanisms of Colitis in the Mdr1a KO Mouse

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

Meeting Report of Taconic's Virtual Workshop: IBD Mouse Modeling — Best Practices for Drug Discovery and Emerging Models

photo from Meeting Report of Taconic's Virtual Workshop: IBD Mouse Modeling — Best Practices for Drug Discovery and Emerging Models

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

BALB/c Il10 Knockout Mice are Useful Tools for IBD and Colitis Research

photo from BALB/<span style='text-transform: lowercase;'>c</span> I<span style='text-transform: lowercase;'>l</span>10 Knockout Mice are Useful Tools for IBD and Colitis Research

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

A Guide to Monitoring NASH Progression in Diet-Induced Mouse Disease Models

photo from A Guide to Monitoring NASH Progression in Diet-Induced Mouse Disease Models

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

Webinar Q&A — Genetically Engineered Mouse Colitis Models for Preclinical Drug Development

photo from Webinar Q&A — Genetically Engineered Mouse Colitis Models for Preclinical Drug Development

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

Planning for Success with NASH mice: proper care and acclimation

photo from Planning for Success with NASH mice: proper care and acclimation

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

Close

Welcome! Tell us a little about yourself