Genetic Discovery Reveals How the Liver Decides Between Sugar and Fat Storage

Genetic Discovery Reveals How the Liver Decides Between Sugar and Fat Storage

A Breakthrough in Liver Metabolism and Energy Storage

A groundbreaking study from the University of Pennsylvania School of Nursing, published in Science Advances, reveals that a single gene, PPP1R3B, plays a vital role in how the liver stores energy, with significant implications for managing conditions like type 2 diabetes and fatty liver disease.

The Role of PPP1R3B in Liver Energy Storage

• What the Gene Does

• The PPP1R3B gene regulates the liver's decision to store energy either as

• Glycogen (a quick-access form of glucose/sugar)

• Triglycerides (a longer-term fat storage form)

• Activity Levels Determine Storage Type

• High PPP1R3B activity = More glycogen stored

• Low PPP1R3B activity = More fat stored

• This balance is critical in maintaining healthy blood sugar and lipid levels.

Connection to Metabolic Diseases

• Large-scale human genomic studies have already linked mutations in PPP1R3B to:

• Type 2 diabetes

• Non-alcoholic fatty liver disease (NAFLD)

• However, the exact mechanisms were previously unclear.

• Key Research Findings

Led by Dr. Kate Townsend Creasy, Assistant Professor of Nutrition Science, this research offers new insights:

PPP1R3B acts like a molecular switch in the liver

• It controls whether the liver:

• Quickly accesses energy (glycogen)
• Stores energy long-term (fat)
• 
  
• Genetically modified mice and cells showed altered efficiency in using glucose vs. fat for energy.
  
  
  

Potential for Precision Nutrition

• This discovery opens doors to personalized treatment strategies for metabolic conditions, such as
• Diets tailored to an individual's genetic profile
• Targeting PPP1R3B activity to optimize energy use and storage
• Reducing the risk of diabetes and liver disease through gene-based interventions

Expert Insights

> “PPP1R3B is like a control switch in the liver. It determines whether energy is stored for immediate use or longer-term. This could revolutionize how we approach metabolic disease treatment.”

 Dr. Kate Townsend Creasy, University of Pennsylvania

Research Collaboration and Support

• This study involved researchers from multiple departments:

• Genetics, Physiology, Translational Medicine, and the Institute for Diabetes, Obesity, and Metabolism

• Supported by the National Institutes of Health (NIH)

Journal Citation

Creasy, K. T., et al. (2025). PPP1R3B is a metabolic switch that shifts hepatic energy storage from lipid to glycogen. Science Advances.

DOI: 10.1126/sciadv.ado3440

Key Takeaways

• PPP1R3B controls how the liver stores energy

• Genetic activity can shift storage from fat to sugar

• Offers promising avenues for gene-based and nutritional therapies

• A major step forward in metabolic disease research