Adipose Tissue Metabolism in Obesity and Insulin Resistance

Adipose tissue plays a central role in systemic energy balance and metabolic health. In obesity, excessive lipid storage in white adipocytes disrupts normal endocrine signalling, leading to impaired insulin sensitivity in peripheral tissues. The hypertrophy and hyperplasia of adipose depots provoke local hypoxia, endoplasmic reticulum stress and the release of proinflammatory adipokines such as tumour necrosis factor-α and interleukin-6. These factors recruit macrophages and other immune cells, establishing low-grade chronic inflammation that interferes with insulin-mediated glucose uptake and lipid handling. Furthermore, an imbalance between lipid storage and lipolysis exacerbates ectopic lipid accumulation in liver and muscle, further compromising insulin signalling cascades. By contrast, brown and beige adipocytes can dissipate energy via uncoupled mitochondrial respiration, offering a potential counterbalance to excess energy intake. Dysregulation of mitochondrial function and impaired browning of white adipose tissue attenuates thermogenic capacity and contributes to energy surplus. At the molecular level, transcriptional regulators including peroxisome proliferator-activated receptors, CCAAT/enhancer binding proteins and PR domain–containing factors coordinate adipocyte differentiation and metabolic gene programmes. A nuanced understanding of these pathways underscores the global significance of adipose tissue metabolism in the pathogenesis of obesity and insulin resistance, while highlighting emerging strategies to modulate adipocyte function for therapeutic benefit.

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Adipose Tissue Metabolism in Obesity and Insulin Resistance publication trend

The graph below shows the total number of articles in adipose tissue metabolism in obesity and insulin resistance across all publications each year (not limited to Nature Index journals).

Technical terms

Adipokines: bioactive proteins secreted by adipose tissue that modulate metabolic and inflammatory pathways.

Insulin resistance: diminished cellular response to insulin, leading to impaired glucose uptake and metabolism.

PPARγ (Peroxisome proliferator-activated receptor gamma): a nuclear receptor that regulates adipocyte differentiation and lipid storage.

Adipose tissue macrophages: immune cells resident in fat depots that contribute to inflammation and metabolic regulation.

Browning: process by which white adipocytes acquire thermogenic characteristics similar to brown adipose cells.

References

1. Effects of mifepristone on adipocyte differentiation in mouse 3T3-L1 cells. Cellular & Molecular Biology Letters (2024).
2. Obesity and type 2 diabetes mellitus: connections in epidemiology, pathogenesis, and treatments. Frontiers in Endocrinology (2023).
3. Obesity is associated with macrophage accumulation in adipose tissue. Journal of Clinical Investigation (2003).
4. The Roles of Adipokines, Proinflammatory Cytokines, and Adipose Tissue Macrophages in Obesity-Associated Insulin Resistance in Modest Obesity and Early Metabolic Dysfunction. PLOS ONE (2016).
5. Brown Fat and Browning for the Treatment of Obesity and Related Metabolic Disorders. Diabetes & Metabolism Journal (2016).