Fibrosis and Metabolic Dysregulation in Adipose Tissue

Adipose tissue is a dynamic organ whose proper expansion and remodelling are essential for energy homeostasis. In obesity and related metabolic disorders, chronic low-grade inflammation, hypoxia and mechanical stress disrupt the balance of matrix synthesis and degradation, leading to fibrosis. Excessive accumulation of collagen and other extracellular matrix components stiffens the tissue, impairs vascular perfusion and alters adipocyte function. Fibrotic remodelling restricts lipid storage capacity, promotes ectopic fat deposition and drives insulin resistance. Moreover, fibrogenic activation of resident progenitors and macrophages sustains a feed-forward loop of myofibroblast recruitment and cytokine release. Together, these processes underlie the transition from adaptive tissue expansion to pathological stiffening, exacerbating metabolic dysregulation and increasing cardiometabolic risk worldwide.

Research from Nature Portfolio

Transcriptomic analysis of white adipocytes under prolonged high-fat feeding has revealed that mature fat cells adopt a fibroblast-like gene signature. This shift entails upregulation of extracellular matrix and cytoskeletal genes alongside suppression of mitochondrial and lipogenic programmes, linking fibrogenic adaptation directly to metabolic decline in obesity. In parallel, investigation of the mechanotransducer pathway in adipocytes has shown that the transcriptional co-activators YAP and TAZ are activated by inflammatory cues and mechanical stress. Loss of YAP/TAZ in white fat triggers apoptosis, lipodystrophy and heightened tissue fibrosis under a western-style diet, highlighting their role in maintaining adipocyte viability and preventing excessive matrix deposition during weight gain.

Fibrosis and Metabolic Dysregulation in Adipose Tissue publication trend

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

Technical terms

Fibrosis: Excessive deposition of extracellular matrix proteins, notably collagens, leading to tissue stiffening and impaired function.

Extracellular matrix (ECM): A network of structural proteins and proteoglycans that provides mechanical support and signalling cues to cells.

Adipocyte: A specialised cell for lipid storage and endocrine signalling within adipose tissue.

Macrophage polarization: The functional activation states of macrophages, ranging from pro-inflammatory (M1) to tissue-remodelling (M2) phenotypes.

Myofibroblast: A contractile cell type that secretes high levels of ECM components during wound healing and fibrosis.

Thermogenesis: The process by which brown or beige adipocytes generate heat through mitochondrial uncoupling.

YAP/TAZ: Transcriptional co-activators regulated by mechanical and inflammatory signals that modulate cell survival and matrix homeostasis.

Transforming growth factor-β (TGFβ): A cytokine that drives fibrogenic differentiation and suppresses adipogenic programmes.

References

1. A macrophage-collagen fragment axis mediates subcutaneous adipose tissue remodeling in mice. Proceedings of the National Academy of Sciences of the United States of America (2024).
2. Defective extracellular matrix remodeling in brown adipose tissue is associated with fibro-inflammation and reduced diet-induced thermogenesis. Cell Reports (2023).
3. A Preliminary Study on Factors That Drive Patient Variability in Human Subcutaneous Adipose Tissues. Cells (2024).
4. The Adipocyte Acquires a Fibroblast-Like Transcriptional Signature in Response to a High Fat Diet. Scientific Reports (2020).
5. YAP and TAZ protect against white adipocyte cell death during obesity. Nature Communications (2020).