Adipokine IL-11/IL-11Ra constrains sphingolipid metabolism to limit the thermogenic capacity of beige adipocytes.
basic_science · Level V
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- Record sourced from PubMed, PMID 42140185.
- Also identified by DOI 10.1016/j.cmet.2026.04.013.
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Abstract
Adipocytes exhibit cellular plasticity by secreting pro-inflammatory cytokines in response to an energy excess. Here, we identify that interleukin (IL)-11 is robustly induced and secreted from adipocytes, especially beige adipocytes upon adrenergic stimulation. IL-11 inhibits adipocyte thermogenesis through binding to IL-11 receptor a (IL-11Ra) and serves as a "brake" to maintain energy homeostasis. Adipocyte-specific IL-11Ra-knockout mice exhibit enhanced whole-body energy consumption and improved glucose and lipid metabolism under a high-fat diet (HFD). Inhibition of IL-11/IL-11Ra signaling enhances sphingosine kinase 1 (Sphk1)-driven production of sphingosine-1-phosphate (S1P), thus remodeling intracellular calcium cycling in beige adipocytes. Notably, treatment with a designed peptide against IL-11Ra in obese mice effectively alleviates fat accumulation and obesity-associated disorders. Taken together, our study defines a physiological and noncanonical mechanism of beige adipocyte-derived IL-11 in energy metabolism, which may serve as a promising target for the treatment of obesity.