Obesity

Obesity, a global epidemic, has become a significant public health concern, leading to an increased risk of numerous comorbidities, including type 2 diabetes, cardiovascular disease, and certain types of cancer. Alfa Cytology is dedicated to leveraging its expertise in cellular metabolism and drug discovery to develop innovative PARP-based therapies for obesity.

PARP as a Therapeutic Target for Obesity

The ADP-ribose modification catalyzed by PARP enzymes has emerged as a crucial regulator of central and peripheral carbohydrate and lipid metabolism. PARP1, PARP2, PARP7, PARP10, and PARP14 have been identified as key players in this process, with PARP1 and PARP2 playing critical roles in adipocyte differentiation and lipid accumulation. By modulating the activity of these metabolic regulators, PARP inhibitors hold the promise of revolutionizing the treatment of obesity and its associated comorbidities.

Fig. 1 The involvement of PARP enzymes in the transcriptional control of white adipogenesis. (Szántó M., et al. 2021)

PARP Inhibitor Development for Fatty Liver Disease

PARP inhibition can effectively combat obesity by targeting two crucial pathways: fat uptake and mitochondrial biogenesis.

• Reduced Fat Uptake
  In vitro studies have demonstrated that PARP inhibition can significantly reduce the uptake and accumulation of fatty acids in adipocytes. The inhibition of PARP1 and PARP2 leads to a downregulation of key lipogenic genes, such as SREBP1, FAS, and ACC, which are responsible for the synthesis and esterification of fatty acids.
• Increased Mitochondrial Biogenesis
  In addition to regulating fat uptake, research has also uncovered the ability of PARP inhibitors to enhance mitochondrial biogenesis in adipocytes. The inhibition of PARP enzymes, particularly PARP1 and PARP2, can activate the AMPK-PGC1α axis, a key signaling pathway that promotes the proliferation and expansion of mitochondria.

Our Services

At Alfa Cytology, our team of highly skilled scientists are dedicated to unraveling the complex mechanisms underlying the relationship between PARP activity and adipose tissue biology. Through our comprehensive suite of preclinical services, we are working tirelessly to develop novel PARP-targeted therapies that can effectively address the root causes of obesity.

Therapeutics Development

• PARP1 Inhibitors Development
• PARP2 Inhibitors Development
• PARP3 Inhibitors Development
• PARP7 Inhibitors Development
• PARP10 Inhibitors Development

Diagnostic Development

• PARPi Responsive Biomarker Discovery Service
• PARPi Resistant Biomarker Discovery Service
• Imaging Service of PARP
• PARP Activity Assay Service

Modeling Services

• Diet-Induced Obesity (DIO) Model
• Genetic Obesity Models
• Humanized Obesity Models

Preclinical Research

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

Alfa Cytology is committed to advancing the field of PARP-targeted therapies for obesity. For more information about our PARP inhibitor development program for metabolic disease or to discuss potential collaborations, please don't hesitate to contact us.

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