Cidea Control of Lipid Storage and Secretion in Mouse and Human Sebaceous Glands

Zhang, Shasha; Shui, Guanghou; Wang, Guanqun; Wang, Chao; Sun, Siyu; Zouboulis, Christos C.; Xiao, Ran; Ye, Jing; Li, Wei

doi:10.1128/mcb.01723-13

Cited by 37 publications

(25 citation statements)

References 47 publications

(88 reference statements)

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“…While Cidea-deficient sebocytes with an impaired lipid production and secretion accumulated a large number of smaller-sized lipid droplets, the overexpression of Cidea in human SZ95 sebocytes resulted in increased lipid storage and an accumulation of large lipid droplets, both of which were correlated positively with human sebum secretion. 50 These results suggest that in leptintreated sebocytes the enlargement of lipid droplets could be considered a marker for increased lipid production and secretion; however, more data on the formation, enlargement, function and fate of these lipid bodies are needed to understand their exact role in (leptin-treated) sebocytes.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2014

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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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2014

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“…In addition to its role in protecting and waterproofing the hair and skin, the SG is important for hair fiber sheath dissociation and the integrity of the hair follicle [45]. Unfortunately, little has been understood about the regeneration of the SG [46]. This is in part because of the lack of a specific marker for recognizing sebocytes.…”

Section: Discussionmentioning

confidence: 99%

Hair Follicle and Sebaceous Gland De Novo Regeneration With Cultured Epidermal Stem Cells and Skin-Derived Precursors

Wang

et al. 2016

Stem Cells Translational Medicine

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Stem cell-based organ regeneration is purported to enable the replacement of impaired organs in the foreseeable future. Here, we demonstrated that a combination of cultured epidermal stem cells (EpiSCs) derived from the epidermis and skin-derived precursors (SKPs) was capable of reconstituting functional hair follicles and sebaceous glands (SG). When Epi-SCs and SKPs were mixed in a hydrogel and implanted into an excisional wound in nude mice, the Epi-SCs formed de novo epidermis along with hair follicles, and SKPs contributed to dermal papilla in the neogenic hair follicles. Notably, a combination of culture-expanded Epi-SCs and SKPs derived from the adult human scalp were sufficient to generate hair follicles and hair. Bone morphogenetic protein 4, but not Wnts, sustained the expression of alkaline phosphatase in SKPs in vitro and the hair follicle-inductive property in vivo when SKPs were engrafted with neonatal epidermal cells into excisional wounds. In addition, Epi-SCs were capable of differentiating into sebocytes and formed de novo SGs, which excreted lipids as do normal SGs. Thus our results indicate that cultured Epi-SCs and SKPs are sufficient to generate de novo hair follicles and SGs, implying great potential to develop novel bioengineered skin substitutes with appendage genesis capacity. STEM CELLS TRANSLATIONAL MEDICINE 2016;5:1695-1706 SIGNIFICANCEIn postpartum humans, skin appendages lost in injury are not regenerated, despite the considerable achievement made in skin bioengineering. In this study, transplantation of a combination of cultureexpanded epidermal stem cells and skin-derived progenitors from mice and adult humans led to de novo regeneration of functional hair follicles and sebaceous glands. The data provide transferable knowledge for the development of novel bioengineered skin substitutes with epidermal appendage regeneration capacity.

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“…In particular, white adipocytes require Cidec/Fsp27 for the formation of unilocular LD since its deficiency results in the accumulation of multilocular small LDs and markedly reduced lipid storage (Nishino et al, 2008;Rubio-Cabezas et al, 2009;Toh et al, 2008). Reduced LD sizes and low lipid storage is also observed in Cideb deficient hepatocytes, Cidea deficient skin sebocytes, brown adipocytes and mammary epithelia cells Wang et al, 2012;Wu et al, 2014b;Zhang et al, 2014;Zhou et al, 2003).…”

Section: Ld Growth Promoted By Atypical Fusionmentioning

confidence: 99%

The size matters: regulation of lipid storage by lipid droplet dynamics

2016

Sci. China Life Sci.

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Adequate energy storage is essential for sustaining healthy life. Lipid droplet (LD) is the subcellular organelle that stores energy in the form of neutral lipids and releases fatty acids under energy deficient conditions. Energy storage capacity of LDs is primarily dependent on the sizes of LDs. Enlargement and growth of LDs is controlled by two molecular pathways: neutral lipid synthesis and atypical LD fusion. Shrinkage of LDs is mediated by the degradation of neutral lipids under energy demanding conditions and is controlled by neutral cytosolic lipases and lysosomal acidic lipases. In this review, we summarize recent progress regarding the regulatory pathways and molecular mechanisms that control the sizes and the energy storage capacity of LDs.

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Cidea Control of Lipid Storage and Secretion in Mouse and Human Sebaceous Glands

Cited by 37 publications

References 47 publications

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

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

Hair Follicle and Sebaceous Gland De Novo Regeneration With Cultured Epidermal Stem Cells and Skin-Derived Precursors

The size matters: regulation of lipid storage by lipid droplet dynamics

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