PPARs and Mitochondrial Metabolism: From NAFLD to HCC

Area of Science:

• Hepatology
• Mitochondrial Biology
• Endocrinology

Background:

• Metabolic diseases like type 2 diabetes, metabolic syndrome, and NAFLD cause significant global mortality, primarily from cardiovascular events and cancer.
• The liver, as the central metabolic organ, plays a crucial role in maintaining whole-body energy homeostasis.
• Mitochondria are key cellular hubs integrating metabolic, hormonal, and inflammatory signals essential for cellular energy and biosynthesis.

Purpose of the Study:

• To review the critical roles of Peroxisome proliferator-activated receptors (PPARs) in regulating liver mitochondrial metabolism.
• To explore the involvement of PPARs in both physiological functions and pathological conditions, including nonalcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC).

Main Methods:

• Literature review focusing on the function of PPARs in liver metabolism.
• Analysis of studies investigating PPARs' impact on mitochondrial function in various liver conditions.
• Synthesis of current knowledge on PPARs' regulatory mechanisms in hepatic energy homeostasis.

Main Results:

• PPARs are key nuclear receptors that orchestrate lipid and glucose metabolism.
• PPARs significantly influence liver mitochondrial function, impacting energy production and substrate utilization.
• Dysregulation of PPARs is implicated in the pathogenesis of metabolic disorders and liver cancer.

Conclusions:

• PPARs are central regulators of liver mitochondrial metabolism.
• Understanding PPARs' function is crucial for developing therapeutic strategies against metabolic diseases and liver cancer.
• Further research into PPARs' pathways can elucidate mechanisms underlying NAFLD and HCC progression.