Leptin promotes a proinflammatory lipid profile and induces inflammatory pathways in human SZ95 sebocytes

Br J Dermatol. 2014 Dec;171(6):1326-35. doi: 10.1111/bjd.13229. Epub 2014 Nov 20.

Abstract

Background: Leptin, the adipocyte-secreted hormone that regulates weight, is known to link lipid metabolism with inflammation in various cell types. However, its role in human sebocytes has not yet been investigated.

Objectives: The purpose of this study was to investigate the effects of leptin in human sebaceous gland biology.

Methods: Expression of the long form of the leptin receptor (Ob-Rb) was detected by real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and immunochemistry. Lipid analysis was by high-performance thin-layer chromatography, gas chromatography-mass spectrometry and time-of-flight mass spectrometer mass detection. Lipid bodies were visualized by BODIPY staining using fluorescent microscopy and measured by flow cytometry. Interleukin (IL)-6 and IL-8 mRNA levels were assessed by real-time qRT-PCR and their release was evaluated by enzyme-linked immunosorbent assay. Cyclooxygenase (COX)-2 and 5-lipooxygenase (LOX) protein expression and phosphorylation of p65 and signal transducer and activator of transcription (STAT)-3 were determined by Western blot analysis.

Results: Expression of Ob-Rb was detected in human sebaceous glands and in cultured human SZ95 sebocytes. The treatment of SZ95 sebocytes with leptin led to enlarged intracellular lipid bodies, increased ratios of unsaturated/saturated fatty acids and decreased vitamin E levels. Further supporting a proinflammatory role, leptin induced COX-2 and 5-LOX expression in SZ95 sebocytes and augmented the production of IL-6 and IL-8 cytokines. On leptin treatment, the STAT-3 and nuclear factor-κB pathways were activated, indicating that these known leptin signalling pathways are active in human sebocytes.

Conclusions: Our findings suggest that leptin signalling may be involved in the proinflammatory regulation of sebaceous lipid metabolism and the induction of inflammatory enzymes and cytokines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arachidonate 5-Lipoxygenase / metabolism
  • Cell Line
  • Cyclooxygenase 2 / metabolism
  • Humans
  • Interleukin-6 / metabolism
  • Interleukin-8 / metabolism
  • Leptin / physiology*
  • Lipid Metabolism / physiology
  • Lipids / pharmacology
  • Lipogenesis / physiology
  • NF-kappa B / metabolism
  • Receptors, Leptin / metabolism*
  • STAT3 Transcription Factor / metabolism
  • Sebaceous Glands / metabolism*
  • Signal Transduction / physiology

Substances

  • Interleukin-6
  • Interleukin-8
  • LEPR protein, human
  • Leptin
  • Lipids
  • NF-kappa B
  • Receptors, Leptin
  • STAT3 Transcription Factor
  • Arachidonate 5-Lipoxygenase
  • Cyclooxygenase 2
  • ALOX5 protein, human