Enhancement of lipid content and inflammatory cytokine secretion in <scp>SZ</scp>95 sebocytes by palmitic acid suggests a potential link between free fatty acids and acne aggravation

Choi, Chong Won; Kim, Ye-Jin; Kim, Ji Eun; Seo, Eun Young; Zouboulis, Christos C.; Kang, Jae Seung; Youn, Sang Woong; Chung, Jin Ho

doi:10.1111/exd.13855

Cited by 27 publications

(35 citation statements)

References 17 publications

(54 reference statements)

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“…Loss of sebum production might also be related to the pathogenesis of other dermatoses such as psoriasis and atopic dermatitis (van Smeden et al ., ; Shi et al ., ; Szántó et al ., ). Furthermore, it seems that certain components of sebum, as well as sebocyte‐derived cytokines and inflammatory mediators, could exacerbate acne (Zouboulis, Jourdan & Picardo, ; Choi et al ., ) or perhaps contribute to comedo formation itself (Motoyoshi, ; Kim, Lee & Lee, ). Therefore, future research needs to identify signals and factors that can modulate sebum composition and sebocyte behaviour, rather than abrogate sebum production entirely (Törőcsik et al ., ; Zákány et al ., ).…”

Section: Final Perspectivesmentioning

confidence: 99%

Neuroendocrinology and neurobiology of sebaceous glands

et al. 2020

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The nervous system communicates with peripheral tissues through nerve fibres and the systemic release of hypothalamic and pituitary neurohormones. Communication between the nervous system and the largest human organ, skin, has traditionally received little attention. In particular, the neuro-regulation of sebaceous glands (SGs), a major skin appendage, is rarely considered. Yet, it is clear that the SG is under stringent pituitary control, and forms a fascinating, clinically relevant peripheral target organ in which to study the neuroendocrine and neural regulation of epithelia. Sebum, the major secretory product of the SG, is composed of a complex mixture of lipids resulting from the holocrine secretion of specialised epithelial cells (sebocytes). It is indicative of a role of the neuroendocrine system in SG function that excess circulating levels of growth hormone, thyroxine or prolactin result in increased sebum production (seborrhoea). Conversely, growth hormone deficiency, hypothyroidism, and adrenal insufficiency result in reduced sebum production and dry skin. Furthermore, the androgen sensitivity of SGs appears to be under neuroendocrine control, as hypophysectomy (removal of the pituitary) renders SGs largely insensitive to stimulation by testosterone, which is crucial for maintaining SG homeostasis. However, several neurohormones, such as adrenocorticotropic hormone and α-melanocyte-stimulating hormone, can stimulate sebum production independently of either the testes or the adrenal glands, further underscoring the importance of neuroendocrine control in SG biology. Moreover, sebocytes synthesise several neurohormones and express their receptors, suggestive of the presence of neuro-autocrine mechanisms of sebocyte modulation. Aside from the neuroendocrine system, it is conceivable that secretion of neuropeptides and neurotransmitters from cutaneous nerve endings may also act on sebocytes or their progenitors, given that the skin is richly innervated. However, to date, the neural controls of SG development and function remain poorly investigated and incompletely understood. Botulinum toxin-mediated or facial paresis-associated reduction of human sebum secretion suggests that cutaneous nerve-derived substances modulate lipid and inflammatory cytokine synthesis by sebocytes, possibly implicating the nervous system in acne pathogenesis. Additionally, evidence suggests that cutaneous denervation in mice alters the expression of key regulators of SG homeostasis. In this review, we examine the current evidence regarding neuroendocrine and neurobiological regulation of human SG function in physiology and pathology. We further call attention to this line of research as an instructive model for probing and therapeutically manipulating the mechanistic links between the nervous system and mammalian skin.

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Section: Final Perspectivesmentioning

confidence: 99%

Neuroendocrinology and neurobiology of sebaceous glands

et al. 2020

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“…[ 2,34–36 ] Like AA and LA, [ 37,38 ] palmitic acid was also shown to increase the levels of sebum lipids that are contained in the sebum in vitro and in vivo . [ 39 ] Free FA become incorporated into wax esters and other neutral lipids, which are synthesized solely by the sebaceous gland. [ 40 ] In addition, free FA significantly increased the levels of pro‐inflammatory cytokines in human sebocytes.…”

Section: Sebum and Acnementioning

confidence: 99%

“…[ 15,36–39 ] The increased secretion of IL6 and IL8 after sebocyte treatment with free FA may be an important link to acne as both these cytokines have been shown to contribute to the formation of acne lesions. [ 2,15,39–41 ] Regulation of stearoyl‐CoA desaturase and fatty acid desaturase 2 expression by linoleic acid and arachidonic acid in human sebocytes leads to enhancement of pro‐inflammatory activity but does not affect lipogenesis. [ 38 ] At last, Toll‐like receptor (TLR)‐2 and TLR4 on sebocyte surface (Figure 4) are activated by exogenous FA and lead to IL6 and IL8 synthesis and release from human sebocytes, [ 34,40,42 ] suggesting an aetiologic of increased sebum production and lipid dysregulation in initiation and/or aggravation of inflammatory processes during acne pathogenesis.…”

Section: Sebum and Acnementioning

confidence: 99%

Endocrinology and immunology of acne: Two sides of the same coin

Zouboulis

2020

Experimental Dermatology

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Current experimental research on acne pathophysiology has revealed a more complicated background than the classically reported four-factor aetiology. Cells of the pilosebaceous unit, which represent the template for the development of acne lesions, seem to be parallelly affected by endocrinological/metabolic factors as well as inflammatory/immunological ones that cooperate in sebocyte differentiation and lipogenesis. Indeed, the unique programme of sebocyte terminal differentiation and death, the so called holocrine secretion, is influenced by inflammatory and metabolic (lipid) signalling with common denominator the selective regulation of peroxisome proliferator-activated receptors. Autophagy provides substrates for energy generation and biosynthesis of new cell structure proteins contributing to the normally increased sebaceous gland metabolic functions, which are also regulated by extracellular calcium signalling, essential lipids and hormones. The ultimate differentiation product of human sebocytes, sebum, co-regulates the inflammatory sebocyte status. Sebum composition is controlled among others by Propionibacterium acnes and other bacteria, sexual hormones, neuropeptides, endogenous opioids and environmental agents, which may function as endocrine disruptors. Diet may also be an important source of substrates for the synthesis of pro-inflammatory and anti-inflammatory sebaceous lipids. Sebum changes might induce inflammation and initiate underlying immune mechanisms leading to acne lesions. Current new therapeutic efforts on acne concentrate on anti-inflammatory/immunologically active concepts, which are able to regulate sebaceous lipogenesis. At last, current molecular studies based on published molecular data sets confirmed the major role of inflammation in acne development.

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“…This is demonstrated, for instance, by recent scholarly reviews on SG physiology, [ 2 ] endocrinology and immunology, [ 3 ] neurobiology, [ 4 ] its roles in acne [ 4,5 ] and beyond acne [ 6 ] and original works on different areas of SG function, including fascinating research on sebaceous lipogenesis. [ 7–22 ] Such a development was unthinkable in the 1960s, when the American master of dermatology, Prof. Albert M. Kligman, has shocked the scientific word with his aphorism “The SG is… a living fossil with a past but not future.”. [ 23 ] This provocative and unsurpassable statement seemed to seal the future of SG research.…”

Section: The First Stepsmentioning

confidence: 99%