Adipose Tissue Inflammation and Insulin Resistance

Adipose tissue serves not only as a lipid reservoir but as an endocrine organ secreting adipokines that regulate systemic energy homeostasis. In the context of caloric excess, hypertrophy of adipocytes precipitates a state of chronic low-grade inflammation. This inflammatory milieu is characterised by increased infiltration of immune cells—most notably pro-inflammatory M1 macrophages—into expanding fat depots. The formation of crown-like structures around dying adipocytes and upregulation of pro-inflammatory cytokines such as tumour necrosis factor-alpha and interleukin-6 disrupts insulin signalling by promoting serine phosphorylation of insulin receptor substrates. Concurrent remodelling of the extracellular matrix further impairs adipocyte function and vascularisation, exacerbating hypoxia and oxidative stress. Collectively, these processes diminish insulin-mediated glucose uptake in adipose and peripheral tissues, driving systemic insulin resistance and elevating the risk of type 2 diabetes and associated comorbidities.

Research from Nature Portfolio

Recent studies have demonstrated that antagonising thrombospondin-1, a matricellular protein upregulated in inflamed fat, can ameliorate obesity-associated metabolic disorders without altering weight gain. Administration of a CD36-derived peptide selectively inhibited thrombospondin-1-mediated macrophage activation in visceral adipose depots, leading to fewer crown-like structures and reduced local and systemic pro-inflammatory cytokine levels. This intervention improved glucose tolerance, enhanced insulin sensitivity and mitigated secondary complications including fatty liver and renal damage. These findings identify thrombospondin-1 antagonism as a promising therapeutic avenue for restoring metabolic homeostasis in obesity.

Adipose Tissue Inflammation and Insulin Resistance publication trend

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

Technical terms

Adipokines: Bioactive peptides secreted by adipose tissue that influence appetite, metabolism and inflammation.

Macrophage polarisation: The process by which macrophages adopt either pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes in response to environmental cues.

Crown-like structures: Ring-shaped accumulations of macrophages encircling necrotic or hypertrophic adipocytes in obese fat tissue.

Insulin resistance: A diminished cellular response to insulin signalling, leading to impaired glucose uptake and elevated blood glucose levels.

Lipolysis: The breakdown of stored triglycerides in adipocytes into free fatty acids and glycerol.

AMP-activated protein kinase (AMPK): A cellular energy sensor that promotes catabolic pathways and inhibits anabolic processes when activated.

References

1. Thrombospondin1 antagonist peptide treatment attenuates obesity-associated chronic inflammation and metabolic disorders in a diet-induced obese mouse model. Scientific Reports (2023).
2. Lack of adipocyte IP3R1 reduces diet-induced obesity and greatly improves whole-body glucose homeostasis. Cell Death Discovery (2023).
3. miR‐467 regulates inflammation and blood insulin and glucose. Journal of Cellular and Molecular Medicine (2021).
4. Scavenger Receptor CD36 Expression Contributes to Adipose Tissue Inflammation and Cell Death in Diet-Induced Obesity. PLOS ONE (2012).