NASH Nuclear Receptors

Nuclear Receptors for Non-Alcoholic Fatty Liver Disease (NASH/NAFLD) Research

Understanding the mechanisms underlying the involvement of nuclear receptors in the pathogenesis of Non-Alcoholic Fatty Liver Disease (NAFLD) or Non-Alcoholic Steatohepatitis (NASH) may oﬀer targets for the development of new treatments for this liver disease. The most common nuclear receptors used in drug and treatment discovery are ligand-activated nuclear receptors, including peroxisome proliferator-activated receptor alpha (PPARα), pregnane X receptor (PXR), and constitutive androstane receptor (CAR), which were first identified as key regulators of the responses against chemical toxicants. Numerous studies using mouse disease models and human samples have revealed critical roles for these receptors and others, such as PPARβ/δ, PPARγ, farnesoid X receptor (FXR), and liver X receptors (LXR), in maintaining nutrient/energy homeostasis in part through modulation of the gut-liver-adipose axis.

NAFLD is associated with altered nuclear receptor function and perturbations along the gut-liver axis. These perturbations include obesity, abnormal hepatic lipid metabolism, increased inflammation, and insulin resistance. Nuclear receptors are essential to understanding the physiology and pathology of liver diseases like NAFLD/NASH, as they are at the crossroads of metabolism, inflammation, and regeneration. Modulation of nuclear receptors has been shown to reduce hepatic steatosis, inflammation, insulin resistance, fibrosis, and obesity, making them attractive – and effective – therapeutic targets.

NASH Nuclear Receptors

Current NASH research indicates drug and treatment discovery relies on Nuclear Receptor activation, specifically:

Our NASH nuclear receptor assay products are cell-based reporter assay systems. They feature engineered nuclear receptor-specific reporter cells prepared using our unique CryoMite™ process. Once thawed, reporter cells are ready for immediate use. Test compounds can be screened for agonist or antagonist activities against human nuclear receptors expressed within the cytoplasm and nuclear environments of healthy, dividing mammalian cells.

INDIGO Biosciences works closely with clients to provide the appropriate Nuclear Receptors for Non-Alcoholic Fatty Liver Disease Research. To empower confident decision-making throughout the discovery process, our technology generates clear single receptor or full-panel screening results. Employing a luminescence-based method and our proprietary CryoMite^™ preservation process, we provide reproducible results lot-to-lot about the efficacy, potency, and selectivity of your compounds, plus comprehensive lab reports that include helpful graphics, summaries, and insights.

Non-Alcoholic Fatty Liver Disease (NAFLD) is characterized by liver inflammation and the buildup of extra fat in liver cells not caused by excessive alcohol consumption. The liver naturally contains some fat, however, when the weight of the fat content of the liver is more than 5-10%, the condition is known as fatty liver (steatosis). NAFLD is the most common liver disorder in developed countries with more than 100 million adults and children affected in the United States alone. NAFLD occurs in people of all races and ethnicities, though research shows it to be most common in those of Latin American descent.

Non-Alcoholic Steatohepatitis (NASH) is the most extreme form of NAFLD, and is a major cause of cirrhosis of the liver and liver cancer.

The majority of people with NAFLD have no symptoms, though some may experience fatigue, dull upper right quadrant abdominal discomfort, and/or mild jaundice. Diagnosis typically occurs following abnormal liver function tests from routine blood test. Common findings are elevated liver enzymes and a liver ultrasound showing steatosis. A liver biopsy is the only widely accepted test for definitively distinguishing NASH from other forms of liver disease. Current estimates indicate that about 20 percent of people with NAFLD have NASH.

According to P&S Market Research, as of March 2017, more than 50 potential therapeutic candidates were in the pipeline. Certain factors - including unknown etiology, complex patho-physiology, and high treatment costs - make understanding how associated nuclear receptors respond and react key to further development.

Liver Foundation

DDNews Special Focus on Nonalcoholic Steatohepatitis; Date of publication: March 2017; DDNews

Nonalcoholic Steathohepatits Therapeutics Market; Date of publication: 2017; P&S Market Research

Treatment of non-alcoholic fatty liver disease; Date of publication: May 2006; BMJournal

The clinical features, diagnosis and natural history of nonalcoholic fatty liver disease; Date of publication: March 2005; Clinics in Liver Disease; vol 8, issue 3