Adipose Tissue Under Pressure: How Cells Signal Stress and Seek Help

What happens when your cells are overwhelmed with energy they can’t handle? 

A fascinating new review by Le Lay and Scherer (2025) explores how adipose tissue (fat) communicates under stress — not with words, but by releasing tiny packages called extracellular vesicles (EVs). These microscopic messengers carry stress signals across the body and may be early warning signs of metabolic imbalance.

Their findings dovetail beautifully with the Exposure-Related Malnutrition (ERM) and stress adaptation framework — a model that views chronic illness not just as damage or deficiency, but as a failure to resolve physiological stress under energy constraints.

🚨 AdEVs: The Cell’s Emergency Release Valve

In the context of obesity or nutrient overload, fat cells (adipocytes) become hypertrophic and inflamed. When they can no longer store or process incoming energy, they begin exporting it — in the form of Adipose-Derived Extracellular Vesicles (AdEVs).

These EVs are not benign. They carry:

• Inflammatory miRNAs

• Toxic lipids like ceramides

• Damaged mitochondrial components

• Stress signals that impair insulin signaling in liver, muscle, and brain

This is a textbook example of substrate misallocation — the body is flush with nutrients, but cannot direct them toward repair and regulation. Instead, it dumps them as metabolic “waste,” triggering dysfunction in other organs. In ERM terms, this reflects Stage 2–3 maladaptation, where stress cannot be resolved, and energy is offloaded instead of utilized.

🔋 Mitochondrial Transfer: The Rescue Mission

Contrast this with another EV-based mechanism: mitochondrial transfer. In energy-starved or damaged tissues, certain cells — like stem cells or healthy adipocytes — can donate functional mitochondria to rescue struggling neighbors.

This process is especially vital in:

• Immune regulation

• Tissue regeneration

• Neuroprotection

• Metabolic adaptation under fasting or cold exposure

It’s a beautiful example of bioenergetic cooperation — a system working to restore balance and resolve stress. In the ERM framework, this represents Stage 1 adaptive recovery or reversal potential.

⚖️ Two Faces of Stress Adaptation: Relief vs. Rescue

Strategy	Trigger	Mechanism	Outcome
AdEV Release	Energy overload	Offloading damaged/toxic cargo	Spreads dysfunction
Mitochondrial Transfer	Energy deficit	Donating functional organelles	Supports recovery

AdEVs act as a “pressure relief valve”, protecting the cell in the short term but often harming the system in the long run. Mitochondrial transfer, by contrast, is like jump-starting a failing engine — costly, but regenerative.

🧠 Why It Matters

Understanding these processes helps us shift from a disease-centered to a resilience-centered model of care. AdEVs could serve as early biomarkers of maladaptive stress — a signal that the system is compensating unsustainably. On the other hand, promoting mitochondrial transfer or preserving its function may become a powerful strategy to restore energy balance and prevent chronic decline.

In the future, therapies could aim to reduce harmful EV signals from overloaded fat cells while enhancing beneficial mitochondrial support across tissues. This dual approach — relieve the burden, and restore the engine — may be key to extending healthspan and reversing chronic fatigue, insulin resistance, and metabolic decline.

📚 Reference

Le Lay, S., & Scherer, P. E. (2025). Exploring adipose tissue-derived extracellular vesicles in inter-organ crosstalk: Implications for metabolic regulation and adipose tissue function. Cell Reports, 44, 115732. https://doi.org/10.1016/j.celrep.2025.115732

#Adipose-Derived Extracellular Vesicles (AdEVs), #Mitochondrial Transfer, #Stress Adaptation, #Exposure-Related Malnutrition (ERM), #Metabolic Crosstalk