Adipose Tissue: Nature Reviews Endocrinology | June 2026

• Adipose tissue is no longer viewed simply as a fat storage organ; it is now recognized as a highly active endocrine and neuro-regulatory organ that coordinates whole-body metabolism.
• Adipose tissue communicates through two major pathways:

Humoral signaling (hormones, metabolites, lipid mediators, cytokines, extracellular vesicles)

Neuronal signaling (sympathetic and sensory nerve networks)

• Adipose-derived humoral factors include:

Adipokines

Lipid mediators

Metabolites

Chemokines

Exosomal microRNAs

• These signals regulate insulin sensitivity, glucose metabolism, lipid utilization, inflammation, vascular health, and overall cardiometabolic homeostasis.
• Sympathetic nerves provide rapid control of adipose tissue function, stimulating:

Lipolysis in white adipose tissue

Thermogenesis in brown adipose tissue

Browning of white adipose tissue

• Sensory nerve fibers act as metabolic sensors, detecting chemical, thermal, and mechanical signals within adipose tissue and relaying information back to the central nervous system.
• This bidirectional communication creates a sophisticated feedback system linking adipose tissue to the brain and peripheral organs.
• Cold exposure activates thermogenic adipose tissue and induces release of specific adipokines and lipid mediators that improve systemic glucose and lipid metabolism.
• Exercise also modifies adipose signaling networks, contributing to many of the metabolic benefits traditionally attributed solely to skeletal muscle.
• Obesity disrupts both endocrine and neural communication within adipose tissue, resulting in:

Adipokine dysregulation

Chronic inflammation

Insulin resistance

Adipose neuropathy

• Similar disturbances are observed in:

Type 2 diabetes

Lipodystrophy

Aging-related metabolic disorders

• Age-related deterioration of adipose signaling may contribute to declining metabolic flexibility and increased cardiometabolic risk.
• Emerging technologies are rapidly transforming adipose tissue research, including:

Single-cell sequencing

Multi-omics platforms

Secretome profiling

Organoid models

Optogenetics

Click chemistry

• These tools are enabling unprecedented characterization of adipose-derived signaling molecules and neural circuits.
• Future therapeutic opportunities may include:

Synthetic adipokine analogues

Lipid mediator–based therapies

Neural circuit modulation

Precision targeting of adipose communication pathways

• The review places adipose tissue at the center of modern metabolic medicine, linking obesity, diabetes, cardiovascular disease, aging, and energy homeostasis through integrated endocrine and neural networks.

Bottom line: Adipose tissue functions as a sophisticated humoral–neuronal communication hub that actively regulates systemic metabolism. Understanding and manipulating these signaling networks may open new therapeutic avenues for obesity, diabetes, cardiometabolic disease, and healthy aging.