From Adipose Dysfunction to Multi-Organ Steatosis: Defining the Metabolic Steatotic Axis

Area of Science:

• Metabolic disorders
• Systemic physiology
• Fatty liver disease (NAFLD) and related conditions

Background:

• Current definitions of steatosis focus narrowly on individual organs.
• Steatosis impacts the liver, pancreas, heart, and skeletal muscle, contributing to metabolic dysfunction.
• Understanding the interconnectedness of these organs is crucial for metabolic health.

Purpose of the Study:

• Introduce the Metabolic Steatotic Axis (MSA) as a unifying framework.
• Describe the dynamic, bidirectional interactions among organs affected by steatosis.
• Provide a new perspective on classifying and treating systemic metabolic dysfunction.

Main Methods:

• Narrative review synthesizing existing evidence.
• Analysis of lipotoxicity, inflammatory signaling, and endocrine cross-talk.
• Conceptual framework development for the MSA.

Main Results:

• The MSA highlights a self-amplifying network accelerating insulin resistance and cardiometabolic risk.
• The MSA concept supports axis-based staging and composite biomarkers for disease burden.
• Phenotypic heterogeneity and organ vulnerability within the MSA are identified.

Conclusions:

• The MSA reframes interventions as systemic modulators, not organ-specific treatments.
• Multi-organ endpoints are needed in clinical trials for metabolic disorders.
• The MSA paradigm can reshape disease classification, therapy, and precision medicine.