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

Abstract

Leptin promotes a pro-inflammatory lipid profile and induces inflammatory pathways in human SZ95 sebocytesRunning head: Leptin in sebaceous gland biology Manuscript word count: 3.153 (materials and methods not included) The authors have nothing to disclose. Bulleted statementsWhat's already known about this topic? Leptin is an adipocyte-secreted hormone that regulates weight. Leptin is known to link lipid metabolism with inflammation in various cell types.This article is protected by copyright. All rights reserved. Sebaceous glands are capable of responding to different stimuli by an altered secretion of lipids and production of inflammatory mediators.What does this study add?Leptin was recognized as a possible pro-inflammatory player in sebaceous gland biology since sebocytes responded to leptin stimulation with pro-inflammatory changes in the sebaceous lipid profile and with an increased expression of inflammatory enzymes and cytokines. SummaryBackground: 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 the study was to investigate the effects of leptin in human sebaceous gland biology.Methods: Ob-Rb expression was detected by real time quantitative RT-PCR and by immunochemistry.Lipid analysis was performed 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. IL-6 and IL-8 mRNA levels were assessed by real time quantitative RT-PCR and their release was evaluated by enzyme-linked immunosorbent assay. COX-2 and 5-LOX protein expressions as well as the phosphorylation of p65 and STAT3 were determined by Western blot analysis.Results: Expression of Ob-Rb was detected in human sebaceous glands and in cultured human SZ95sebocytes. The treatment of SZ95 sebocytes with leptin led to an enlargement of intracellular lipid bodies, This article is protected by copyright. All rights reserved.increased the ratios of unsaturated/saturated fatty acids and decreased vitamin E levels. Further supporting a pro-inflammatory role, leptin induced COX-2 and 5-LOX expression in SZ95 sebocytes and augmented the production of IL-6 and IL-8 cytokines. Upon leptin treatment, STAT-3 and NF-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 pro-inflammatory regulation of sebaceous lipid metabolism and in the induction of inflammatory enzymes and cytokines.

Beyond acne: Current aspects of sebaceous gland biology and function

“…While leptin deficient (ob/ob) mice were found to exhibit an increased sebaceous gland size suggesting that leptin is involved in the lipid production/secretion of sebocytes [152], leptin treatment of SZ95 sebocytes led to a "pro-acne" change in the sebaceous lipid profile via increasing the amounts of NFκB. These results all support that leptin could be a possible contributor in linking nutrition with acne, however the conditions and the possible pathways still need to be confirmed in more details [129]..…”

Inhibition of the sterol regulatory element‐binding protein pathway suppresses hepatocellular carcinoma by repressing inflammation in mice

“…In addition, ER stress can increase lipogenesis and oxidative stress, which make hepatocytes prone to cell death . The dead hepatocytes then release proinflamatory mediators, including IL‐1α and lipids, to activate liver Kupffer cells to produce more cytokines and growth factors, including IL‐1β, IL‐6, and TNFα. The debris of hepatocytes did increase expression levels of IL‐1β and IL‐6 in Kupffer cells (http://onlinelibrary.wiley.com/doi/10.1002/hep.29018/suppinfo).…”

Pathogenesis of acne

“…Saját eredményeink alapján ebbe a folyamatba illeszkedhet be a "jóllakottság hormon" leptin is, mint pro-acne ágens, mely hasonlóan az acnés betegek faggyújában ismertetettekhez, kísérleteinkben megnövelte a telítetlen zsírsavak arányát a faggyúban. Továbbá a szébumban megtalálható legfőbb antioxidáns az E vitamin leptin kezelés hatására történő csökkesése is felveti annak a lehetőségét, hogy komoly szereppel bírhat a gyulladásos acnés bőrtünetek esetében tapasztalt megváltozott faggyú-összetétel kialakításában, példát mutatva arra, hogy molekuláris szinten hogyan kapacsolódhat össze a táplálkozás és a betegség (20).…”