Gene network based analysis identifies a coexpression module involved in regulating plasma lipids with high-fat diet...

Area of Science:

• Genetics
• Metabolic Diseases
• Molecular Biology

Background:

• Plasma lipid levels are influenced by genetic variations and environmental factors like diet-induced weight gain.
• Limited understanding exists on how these factors interact to affect molecular networks regulating plasma lipids.

Purpose of the Study:

• To investigate the impact of weight gain as an environmental stressor on plasma lipids using the BXD mouse model.
• To identify gene networks that respond to obesogenic diets and influence plasma lipid levels.

Main Methods:

• Examined coexpression networks in nonobese and obese mouse livers.
• Identified an obesity-associated module linked to plasma lipid levels and enriched for inflammation and lipid homeostasis genes.
• Utilized correlation analysis and Mendelian randomization to assess causal links in humans.

Main Results:

• An obesity-associated gene module responsive to an obesogenic diet was identified.
• Key regulatory genes including PPARG, CIDEG, and CD36 were identified as drivers of this module.
• PPARG emerged as a potential master regulator, targeting numerous hub genes within the module.
• The module's activation was causally linked to human lipid metabolism.

Conclusions:

• Gene-environment interactions, specifically diet-induced weight gain, significantly impact plasma lipid metabolism through specific molecular networks.
• The identified obesity-associated module and its regulators offer potential targets for understanding and treating dyslipidemia.
• Findings suggest novel biomarkers and therapeutic strategies for managing lipid disorders.