Metaflammation's Role in Systemic Dysfunction in Obesity: A Comprehensive Review

Area of Science:

• Immunology
• Metabolic Science
• Endocrinology
• Epigenetics

Background:

• Obesity is redefined as a complex systemic disease involving metabolic, neuroendocrine, immunological, and epigenetic dysregulation.
• Adipose tissue is a dynamic endocrine and immune organ; its expansion drives chronic inflammation ('metaflammation'), impacting insulin signaling and leading to insulin resistance, type 2 diabetes, and cardiovascular disease.
• Gut microbiota dysbiosis and epigenetic modifications further exacerbate systemic dysfunction, affecting hypothalamic function, hormone resistance, and reproductive health.

Purpose of the Study:

• To integrate molecular, neuroendocrine, and immunometabolic factors in understanding obesity.
• To reframe obesity as a comprehensive expression of systemic dysfunction.
• To advocate for a paradigm shift towards personalized, multi-targeted interventions for obesity.

Main Methods:

• Review of current understanding of obesity's molecular, neuroendocrine, and immunometabolic underpinnings.
• Integration of data on inflammation pathways (NF-kB, NLRP3 inflammasome), immune cell infiltration, gut microbiota, and epigenetic modifications.
• Analysis of the impact on insulin signaling, metabolic endotoxemia, neuroendocrine regulation, and reproductive health.

Main Results:

• Obesity involves chronic, low-grade inflammation ('metaflammation') driven by dysfunctional adipose tissue.
• Gut microbiota dysbiosis and epigenetic changes contribute significantly to obesity's systemic effects.
• Existing research highlights the interconnectedness of metabolic, immune, and epigenetic axes in obesity pathogenesis.

Conclusions:

• Obesity is a multifaceted systemic disease requiring an integrated perspective beyond conventional weight management.
• Personalized, multi-targeted interventions modulating the immunometabolic network, microbiota, and epigenetics are essential.
• Addressing the global obesity epidemic necessitates a translational approach focusing on these interconnected biological systems.