Obese adipocytes show ultrastructural features of stressed cells and die of pyroptosis

Antonio Giordano, Incoronata Murano, Eleonora Mondini, Jessica Perugini, Arianna Smorlesi, Ilenia Severi, Rocco Barazzoni, Philipp E. Scherer, Saverio Cinti

Research output: Contribution to journalArticle

99 Scopus citations

Abstract

We previously suggested that, in obese animals and humans, white adipose tissue inflammation results from the death of hypertrophic adipocytes; these are then cleared by macrophages, giving rise to distinctive structures we denominated crown-like structures. Here we present evidence that subcutaneous and visceral hypertrophic adipocytes of leptin-deficient ( ob/ob and db/db ) obese mice exhibit ultrastructural abnormalities (including calcium accumulation and cholesterol crystals), many of which are more common in hyperglycemic db/db versus normoglycemic ob/ob mice and in visceral versus subcutaneous depots. Degenerating adipocytes whose intracellular content disperses in the extracellular space were also noted in obese mice; in addition, increased anti-reactive oxygen species enzyme expression in obese fat pads, documented by RT-PCR and immunohistochemistry, suggests that ultrastructural changes are accompanied by oxidative stress. RT-PCR showed NLRP3 inflammasome activation in the fat pads of both leptindeficient and high-fat diet obese mice, in which formation of active caspase-1 was documented by immunohistochemistry in the cytoplasm of several hypertrophic adipocytes. Notably, caspase-1 was not detected in FAT-ATTAC transgenic mice, where adipocytes die of apoptosis. Thus, white adipocyte overexpansion induces a stress state that ultimately leads to death. NLRP3-dependent caspase-1 activation in hypertrophic adipocytes likely induces obese adipocyte death by pyroptosis, a proinflammatory programmed cell death.

Original languageEnglish (US)
Pages (from-to)2423-2436
Number of pages14
JournalJournal of lipid research
Volume54
Issue number9
DOIs
StatePublished - Sep 1 2013

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Keywords

  • Adipose tissue
  • Diabetes
  • Electron microscopy
  • Inflammation
  • Obesity

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

Cite this

Giordano, A., Murano, I., Mondini, E., Perugini, J., Smorlesi, A., Severi, I., Barazzoni, R., Scherer, P. E., & Cinti, S. (2013). Obese adipocytes show ultrastructural features of stressed cells and die of pyroptosis. Journal of lipid research, 54(9), 2423-2436. https://doi.org/10.1194/jlr.M038638