Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is a growing global health concern, with an estimated prevalence of 25% worldwide. NAFLD is characterized by the accumulation of fat in the liver, which, if left untreated, can progress to the more severe form of the disease, non-alcoholic steatohepatitis (NASH). Alfa Cytology is dedicated to exploring the potential of PARP inhibitors for the treatment of fatty liver disease.

PARP as a Therapeutic Target for Fatty Liver Disease

PARP is a class of enzymes that play key roles in a variety of cellular processes, including DNA repair, gene regulation, and metabolic homeostasis. Emerging evidence suggests that dysregulated PARP activity is strongly associated with the development and progression of non-alcoholic fatty liver disease (NAFLD) and its more severe form, non-alcoholic steatohepatitis (NASH). Increased PARP activity contributes to oxidative stress and inflammation in the liver, promoting lipid accumulation and damage. The deletion of PARP2 has been shown to enhance fatty acid and triglyceride synthesis, while also increasing mitochondrial biogenesis and fatty acid oxidation through the upregulation of key transcription factors.

Fig. 1 An overview of the PARP-mediated pathologies of fatty liver disease. (Szántó M., et al. 2021)

PARP Inhibitor Development for Fatty Liver Disease

PARP inhibitors can reduce liver damage, triglyceride accumulation, and inflammation, highlighting their potential as a therapeutic strategy. For example, in vitro studies have shown that the inhibition of PARP1 and PARP2 can significantly improve lipid homeostasis, reduce inflammation, and mitigate hepatocyte injury in cell-based models of fatty liver disease.

Experimental Model	Disease Modelled	PARP Inhibitor	Effects
AML12 hepatocytes	Fatty liver Disease	Olaparib	Increased cellular bioenergetics, induction of mitochondrial biogenesis and induction of lipolysis-related genes

Our Services

Leveraging our deep understanding of PARP biology and its role in fatty liver disease, Alfa Cytology offers a comprehensive suite of preclinical services to support the development of PARP-targeted therapies for NAFLD and NASH. Our services include but are not limited to:

Therapeutics Development

Our team of experienced scientists work closely with you to identify, optimize, and validate novel PARP inhibitor candidates for the treatment of NAFLD.

Diagnostic Development

Our team utilizes the comprehensive insights gained from our preclinical research to identify novel biomarkers and develop cutting-edge diagnostic assays

Preclinical Research

Our extensive experience enables us to provide you with high-quality data and insights to accelerate your drug discovery and development efforts.

Cell-Based Assays
Mechanistic Studies
Efficacy Evaluation
ADME Evaluation
Toxicological Profiling

Our Modeling Services of Fatty Liver Disease

In Vitro Models

Immortalized cell lines (HepG2, HuH7, HepaRG)
Primary human hepatocytes (PHH)
Hepatocyte-like cells (derived from stem cells)
Organoids
Liver-on-a-chip

In Vivo Models

Genetic mouse models (e.g. ob/ob, db/db)
Diet-induced mouse models (e.g. high-fat, high-cholesterol, methionine-choline deficient)
Non-rodent models (e.g. hamsters, guinea pigs, nonhuman primates)

If you are interested in exploring the potential of PARP inhibitors for the treatment of non-alcoholic fatty liver disease, we invite you to connect with our team at Alfa Cytology. Our experts are dedicated to collaborating with researchers and pharmaceutical companies to advance the field of NAFLD therapeutics and improve patient outcomes. Please don't hesitate to contact us to discuss how we can support your research and drug development initiatives.

Reference

Szántó M., Gupte R., and et al. PARPs in lipid metabolism and related diseases. Prog Lipid Res. 2021, 84: 101117.

For research use only. Not intended for any clinical use.