Angiogenesis and Metabolic Regulation in Adipose Tissue

Adipose tissue is a dynamic endocrine organ whose metabolic functions extend beyond energy storage to include hormone secretion and thermogenesis. Its expansion and remodelling depend on the formation of new blood vessels through angiogenesis, which ensures adequate oxygen and nutrient delivery and facilitates lipid exchange. In white adipose tissue (WAT), excessive hypertrophy can outstrip vascular supply, leading to local hypoxia, inflammation and metabolic dysfunction. Conversely, brown adipose tissue (BAT) relies on dense vascular networks to support rapid fuel oxidation and heat production via uncoupling protein-1. Endothelial cells in both depots communicate with adipocytes through angiocrine and paracrine signals, modulating adipocyte differentiation, lipid handling and mitochondrial activity. The balance of pro-angiogenic factors such as vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and stem cell factor (SCF) against anti-angiogenic regulators determines tissue perfusion, adipocyte phenotype and systemic glucose homeostasis. Emerging strategies that harness vascular remodelling to promote adipose tissue browning or restore healthy WAT expansion hold promise for combating obesity, insulin resistance and cardiovascular disease on a global scale.

Research from Nature Portfolio

Recent studies have elucidated endothelial-derived factors that directly influence adipocyte metabolism. One investigation demonstrated that stem cell factor (SCF) secreted by endothelial cells activates c-Kit signalling in brown adipocytes, upregulating lipogenic enzymes when thermogenesis is suppressed. Endothelial-specific deletion of SCF or adipocyte deletion of c-Kit attenuated lipid droplet enlargement under denervation or thermoneutral conditions, highlighting a novel angiocrine axis that governs lipid accumulation in BAT. A foundational study revealed that endothelial production of platelet-derived growth factor-CC (PDGF-CC) orchestrates angiogenesis-dependent thermogenesis in beige fat. Loss of endothelial PDGF-CC or its receptor impaired the browning of white depots, while PDGF-CC stimulation enhanced uncoupling protein-1 expression in both murine and human adipocyte precursors, establishing a paracrine mechanism for vascular control of energy expenditure.

Angiogenesis and Metabolic Regulation in Adipose Tissue publication trend

The graph below shows the total number of articles in angiogenesis and metabolic regulation in adipose tissue across all publications each year (not limited to Nature Index journals).

Technical terms

Adipose tissue: A connective tissue specialised for lipid storage, endocrine signalling and thermogenesis.

Angiogenesis: Formation of new blood vessels from existing vasculature to supply oxygen and nutrients.

Angiocrine signalling: Release of growth factors and cytokines by endothelial cells that regulate neighbouring cell functions.

Browning: The induction of thermogenically active beige adipocytes within white fat depots.

Paracrine signalling: Communication in which cells secrete factors that act on adjacent cells within the same tissue.

Thermogenesis: Heat production by specialized cells, notably brown and beige adipocytes, via mitochondrial uncoupling.

References

1. Endothelial cell-derived stem cell factor promotes lipid accumulation through c-Kit-mediated increase of lipogenic enzymes in brown adipocytes. Nature Communications (2023).
2. Endothelial PDGF-CC regulates angiogenesis-dependent thermogenesis in beige fat. Nature Communications (2016).
3. Non-invasive optoacoustic imaging of dermal microcirculatory revascularization in diet-induced obese mice undergoing exercise intervention. Photoacoustics (2024).
4. Adipose Tissue Paracrine-, Autocrine-, and Matrix-Dependent Signaling during the Development and Progression of Obesity. Cells (2023).
5. Angiogenesis in Adipose Tissue: The Interplay Between Adipose and Endothelial Cells. Frontiers in Physiology (2021).