Accepted: 16 March 2017

DOI: 10.1111/jocd.12345

REVIEW ARTICLE

A review of the role of sebum in the mechanism of acne

pathogenesis

Xinchao Li BS1 | Congfen He PhD1 | Zhou Chen MD2 | Cheng Zhou MD2 |
Yao Gan BS1 | Yan Jia PhD1

1
Beijing Key Laboratory of Plant Resources
Research and Development, School of Summary
Science, Beijing Technology and Business Acne is one of the most common skin disorders, and its occurrence is closely related
University, Beijing, China
2 to many factors, including sebum secretion, hormone levels, bacterial infection, and
Department of Dermatology, Peking
University People’s Hospital, Beijing, China inflammatory reactions. Among these, changes in sebum secretion are believed to
be one important factor of acne. Increased sebum secretion can induce acne occur-
Correspondence
Yan Jia, Beijing Key Laboratory of Plant rence, and increasing evidence indicates sebum component changes are also
Resources Research and Development,
strongly related to acne occurrence. Recently, developments in lipidomics have pro-
School of Science, Beijing Technology and
Business University, Beijing, China. vided effective lipid analysis methods. These can help elucidate the effects of differ-
Email: jiayan@btbu.edu.cn
ent types of sebum on acne occurrence and provide a theoretical basis for research
Funding information on the mechanisms of acne pathogenesis and treatment.
This work was supported by National
Natural Science Foundation of China
KEYWORDS
(31501415); grants from Scientific Research
Project of Beijing Educational Committee
acne, lipidomics, sebum
(SQKM201610011008); and grants from
China Cosmetic Collaborative and Innovation
Center, BTBU(19008001060).

1 | EPIDEMIOLOGICAL ACNE RESEARCH
Acne is a chronic inflammatory skin disorder of the hair follicle
sebaceous glands.1 Acne generally occurs at skin regions with copi-
ous lipid secretion and clinically presents as comedones, papules,
pustules, nodules, and other various forms of skin lesions. Epidemi-
ological studies across multiple nationalities and races have
revealed that adolescents have the highest acne incidence, there
are slight differences in acne incidence between men and women,
most acne cases are mild, and acne most commonly occurs on the
face, chest, and back.
Elewski et al.2 investigated 1013 Americans aged 20-29 years
and found the incidence of acne in men and women was 42.5% and
50.9%, respectively. Suh et al.3 investigated 693 Korean children
aged 7-12 years and found an average acne incidence rate of 36.2%,
with a diagnosis rate of 23.8% in younger children (7-9 years) and a
diagnosis rate of 47.4% in older children (10-12 years). A study of
Nigerian students found that 68.8% of the students had acne, with
girls accounting for 50.9% of the population.4 Among these students,
most (65.5%) had mild acne, whereas only 27.3% and 7.3% had mod-
erate and severe acne, respectively.
The results of epidemiological studies of acne in China are similar
to those in other countries. For example, Zheng et al.5 investigated
2015 Chinese students and found that 77.1% had a history of acne
and the average age at the time of the first event was 13.41.4 years.
A study in university students found that the total incidence of acne
was 38.4%, of which 45.2% cases were in men and 32.0% in women;
most cases were mild or moderate.6 Gao7 analyzed data from 203
patients with acne and found that the location of acne occurrence was
most commonly on the cheeks and forehead, followed by the back and
lower jaw, with the chest and mouth area being less common.
2 | RESEARCH DEVELOPMENTS IN
MECHANISMS OF ACNE PATHOGENESIS
Current research suggests that acne occurrence is primarily related
to factors such as sebum secretion, hormone levels, bacterial

J Cosmet Dermatol. 2017;1–6. wileyonlinelibrary.com/journal/jocd © 2017 Wiley Periodicals, Inc. | 1

2 |
infection, and inflammatory reactions.1,8 In addition, it is also related
to blood lipids,9 diet,1 and degree of obesity.3
2.1 | Sebum
Sebum changes are believed to be the most critical factors for acne
occurrence.10 Increased sebum secretion can induce acne occur-
rence, and increasing evidence shows changes in sebum components
are clearly correlated with acne occurrence. These studies would be
discussed in Section 3.
2.2 | Hormone levels
Patients with acne have higher testosterone and 5a-dihydrotestos-
terone levels than do unaffected individuals,11 suggesting a relation-
ship between androgens and acne occurrence. Research has
suggested high androgen levels can enhance sebum secretion,
thereby inducing acne occurrence12; however, other research has
suggested the androgen induction of acne occurrence is independent
of sebum.9 Bakry et al.9 found no obvious difference in sebum levels
between nonobese, nonhirsute female patients with acne and normal
individuals. However, total testosterone, free testosterone, and pro-
gesterone levels were increased in patients with acne, and free
testosterone and sex hormone-binding globulin levels were also
13
increased in patients with severe acne. Riyanto et al. used soy iso-
flavones to inhibit the activity of 3b-hydroxysteroid dehydrogenase,
7b-hydroxysteroid dehydrogenase, and 5a-reductase; they found
“active” androgen levels could be decreased and that this reduced
acne occurrence.
In addition, interesting research has proposed the ratio between
the index and ring fingers (2D:4D) is correlated with the develop-
ment of acne due to its relationship with androgens.14 Female
patients with acne have a lower 2D:4D ratio than do unaffected
women. Furthermore, lower 2D:4D ratios in the left hand correlate
with more severe acne, and lower 2D:4D ratios in the right hand
correlate with longer acne events. Unal et al.15 found the right-hand
2D:4D ratio in female patients with acne was positively correlated
with free androgen index and prolactin values and negatively corre-
lated with sex hormone receptor levels. The left-hand 2D:4D ratio in
female patients with acne was positively correlated with acne event
duration and follicle-stimulating hormone values. These results show
that 2D:4D ratio may serve as a “predictive signal” of acne develop-
ment, duration, and severity.
2.3 | Bacterial infection
Propionibacterium acnes is the skin-colonizing bacterium considered
to be closely related to acne occurrence; it can enhance sebum
secretion and inflammation. It was originally isolated from the skin
16
of patients with acne and is a lipophilic bacillus bacterium. Iinuma
et al.17 showed P. acnes cytoplasmic and formalin-treated cell wall
extracts could promote sebum production in hamster sebaceous
gland cells in vitro and in vivo. Vowels et al.18 used P. acnes and its
LI ET AL.
supernatant to induce human THP-1 and U937 monocytes and
peripheral blood monocytes and found IL-1b, TNF-a, and IL-8
expression levels were significantly increased. In addition, P. acnes
can promote T-cell division, stimulate T-cell pro-inflammatory factor
release,19 and stimulate Toll-like receptor (TLR)-2 in macrophages,
thereby promoting inflammation.20
2.4 | Inflammatory reactions
In the mechanism of acne occurrence, the immune response is related
to high expression levels of IL-1a, TLR, and IL-2 receptor in hair follicle
sebaceous gland units.21 Skin lesions from healing acne scars exhibit a
high proportion of skin-homing T cells, macrophage invasion, high
expression of human leukocyte antigen, and capillary proliferation dur-
ing the regression period,22 suggesting that delayed hypersensitivity
reactions participate in the inflammatory mechanism of acne.
2.5 | Other factors
Acne occurrence is also correlated with diet, lifestyle, and other fac-
tors. Recently, the relationship between blood lipid levels and acne
has been investigated. Bakry et al.9 found nonobese, nonhirsute
Egyptian female patients with acne had significantly increased total
cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C)
levels compared with those of unaffected individuals, whereas high-
density lipoprotein cholesterol (HDL-C) and apolipoprotein (AppA-1)
levels were significantly lower in patients with acne. Hao et al.23
obtained similar findings, where TC, LDL-C, and lipoprotein LP(a)
levels were significantly higher in male and female patients with sev-
ere acne than in unaffected individuals. This correlation provides a
new line of thinking for further investigation of the mechanism of
acne pathogenesis and treatment methods.
3 | RELATIONSHIP BETWEEN ACNE
OCCURRENCE AND SEBUM
Among factors affecting the occurrence of acne, sebum is one of the
most closely related factor. The sebum content in different facial
regions (eg, T-zone, U-zone, and O-zone) has different relationships
with acne occurrence, and changes in different sebum components
affect the occurrence of acne through different pathways.
3.1 | Lipid content
Increased sebum secretion is an important factor in acne pathogene-
sis. A study by Kim et al.24 of 36 patients with acne and 47 individu-
als without acne indicated that, among five facial regions (forehead,
nose, chin, left cheek, and right cheek), patients with acne had signif-
icantly higher sebum levels in the nose region than did individuals
without acne. These differences induced higher T-zone sebum levels
and mean facial sebum excretions (MFSE) in patients with acne com-
pared with those in patients without acne, indicating more copious
LI ET AL.
sebum excretion in patients with acne. Another study of Korean
female patients with acne and patients without acne found T-zone,
U-zone, and overall face sebum secretions were higher in patients
25
with acne than in the control group.
The sebum contents of different facial regions (T-zone, U-zone,
and O-zone) also have different relationships with acne. A study of
the sebum content of 914 Korean patients with acne by Choi
et al. 10
found a positive correlation between facial sebum levels and
acne severity. In young (<25 years) patients with acne, sebum levels
in the U-zone affected inflammatory damage and the number of
acne lesions, whereas in older (>25 years) patients with acne, the
effect was seen in the T-zone; male patients with acne were more
susceptible to the effects of increased facial sebum levels. Consis-
tent with these findings, a study of Nigerian adolescents by Okoro
et al.6 also found a positive correlation between average sebum
levels and acne lesions in the U-, but not the T-zone. However, one
study suggested that the oral region (O-zone) exhibited different
characteristics with respect to the development of acne.26 This study
divided the facial region into an NT-zone (the traditional T-zone
minus the area around the mouth), a U-zone, and an O-zone. In the
O-zone, men had more acne lesions than did women; additionally,
the average area-weighted (AW) density of acne lesions decreased
with increasing age in the NT- and U-zones as well as in the entire
facial region. However, the average AW density of acne lesions
remained highest in the O-zone. Therefore, this study suggested that
the NT-zone could serve as a substitute for the traditional T-zone
and the O-zone could be considered an independent region when
dividing the face into regions for analysis of acne.
In addition, a study of the correlation between the location of
pathological changes and regional sebum differences revealed that
increased sebum secretion was not correlated with the number of
acne lesions.25 Furthermore, the view that increased sebum induces
more noninflammatory and inflammatory acne lesions is controver-
27
sial. A growing body of sebum research supports the notion that
certain sebum components, rather than the total amount of sebum,
are the key factors responsible for inducing acne development.
3.2 | Lipid composition
Sebum can be categorized as sebaceous lipids and extracellular lipids
based on their origin and composition.28 Sebaceous lipids are
secreted from sebaceous glands and form a layer of hydrolipidic film
together with sweat secreted by sweat glands. These components
moisturize the skin, prevent moisture loss, and resist harm from for-
eign matter. The main lipid components include squalene, triglyc-
erides (TG), free fatty acids (FFAs), wax ester, cholesterol (CHOL),
and cholesteryl ester. Extracellular lipids mainly refer to lipids among
stratum corneum, mainly including ceramides (CERs), FFAs, and
CHOL. Lamellar bodies eventually released lipid precursors and lipid
synthases into extracellular spaces of stratum corneum, and then the
lipid precursors were catalyzed by the lipid synthases to produce
extracellular lipids. Lipid composition changes are important factors
contributing to inflammation in acne.
| 3
3.2.1 | Fatty acids
A study of male patients with acne conducted by Smith et al.29
showed that acne-affected and normal skin locations have signifi-
cantly different ratios of saturated to unsaturated fatty acids. The
C16:0/C16:1 ratio of triglyceride and wax ester was significantly
higher on the surface of acne-affected skin compared with that on
normal skin. Ottaviani et al.30 further showed increased sebum
excretion and the severity of clinical presentation were related to
changes in the ratio of monounsaturated fatty acids to total fatty
acids, indicating the degree of fatty acid saturation may play an
important role in acne pathogenesis and lipid synthesis. Currently,
changes in the ratio of saturated and unsaturated fatty acids are
considered to regulate follicular inflammation and congenital immune
reactions.31,32 But Akaza33 research shows that fatty acid composi-
tions of TG and FFA in sebum depend on the amount of TG and do
not differ in the presence or absence of acne vulgaris.
Sapienic acid,34 16:1n-10, is the most abundant unsaturated fatty
acid on human skin where its synthesis is mediated by fatty acid
desaturase 2 (FADS2) in the sebaceous glands. And the role of sapi-
enic acid (16:1, D6),35 an abundant sebum fatty acid, in the patho-
genesis of acne is controversial. Some researchers consider its
presence to be related to increased sebum levels29; however, some
reports claim it can effectively inhibit the bacteria commonly associ-
ated with acne.36–38
3.2.2 | Squalene content
Squalene by-products,39 mostly under peroxidized forms, lead to
comedogenesis, contribute to the development of inflammatory
acne, and possibly modify the skin relief (wrinkling). A study of men
with different levels of acne (no acne or moderate-to-severe acne)
conducted by Pappas et al.40 revealed reduced free fatty acid levels
and increased triglyceride and wax ester/cholesterol ester levels in
patients with acne. The difference in squalene levels was the great-
est between the two groups, with the acne group having levels 2.2
times greater compared with those of the control group. In addition,
the total sebaceous gland lipid content was 20% and 15% in the
acne and control groups, respectively. Therefore, increased squalene
content can serve as a lipid marker of acne-affected skin. The
changes in lipid content observed in patients with acne,30 especially
squalene oxidation, have been confirmed to play important roles in
the development of pimples, bacterial toxicity, and inflammatory
reactions. For example, the study by Capitanio et al.41indicates that
the percentage of oxidized squalene was significantly elevated in the
sebum of patients with mild comedonal acne.
3.2.3 | Linoleic acid content
Many independent studies30,42,43 have found lower linoleic acid
levels in the skin surface lipids of patients with acne. Reduced
sebum linoleic acid content is believed to affect sphingolipid synthe-
sis.29 Patients with acne had only 6% linoleic acyl ceramides,42,44,45
4 |
whereas the epidermis of normal individuals contained 45% linoleic
acyl ceramides. Linoleic acid in sphingolipids is considered a possible
participant in follicular hyperkeratosis,42 a key step in pimple forma-
tion. In addition, low linoleic acid levels compromise the barrier func-
tion of the skin,46 thereby increasing the skin permeability to acne-
causing inflammatory substances. On the other hand, high linoleic
acid levels can prevent acne development,47,48 and local application
can even reduce pimple formation by inhibiting 5a-reductase activ-
ity，such asγ-linoleic acid could be used as adjuvant treatments for
acne patients.49
3.2.4 | Causes of lipid mediator changes
Some skin lipid components can serve as signaling molecules; these
cause changes in related signaling pathways, inducing enzyme modi-
fication and lipid peroxidation. Among these, some lipid mediators
can affect the differentiation and lipid synthesis of sebaceous gland
cells50 by stimulating the peroxisome proliferator-activated receptor
(PPAR) signaling pathway.48 PPARa is related to b-oxidation of fatty
acids and lipid metabolism, whereas PPARc is related to lipid synthe-
sis. For example, 5-lipoxygenase is much more highly expressed in
patients with acne than in healthy individuals, cyclooxygenase-2 and
PPARc expression show upward trends in the skin of patients with
acne, and the 5-lipoxygenase inhibitor zileuton can reduce acne
51
lesions by inhibiting pro-inflammatory lipid mediators.
Arachidonic acid content is increased at skin lesions in patients
with acne. Alestas et al.52 suggested 5-lipoxygenase could use
arachidonic acid as a substrate for the synthesis of leukotriene, an
inflammatory mediator and potent neutrophil attractant, thus induc-
ing inflammatory reactions. In addition, arachidonic acid can serve as
a signaling molecule to upregulate 5-lipoxygenase expression.52
Treatment of SZ95 sebaceous gland cells with arachidonic acid stim-
ulated 5-lipoxygenase expression and enhanced leukotriene synthe-
sis.52 In addition, arachidonic acid can induce IL-6 and IL-8
expression, further inducing inflammation. Furthermore,lipopolysac-
charide (LPS) from Gram-negative bacteria has been reported to
53
directly increase inflammation by augmenting cyclooxygenase 2,
prostaglandin F(2a) (PGF(2a)), and the PGF(2a)-mediated progelati-
nase A/promatrix metalloproteinase 2 (proMMP-2) production in
sebaceous glands as well as epidermal inflammatory events in skin
disorders including acne and folliculitis.
In addition, the skin surface lipid oxidant/antioxidant ratio is a
1
primary factor in the induction of acne inflammation. Lipid peroxide
content is significantly higher in acne lesions than in normal skin.
Acetylcholine also plays an important role in the physiology of
54
human sebaceous glands. In vivo and in vitro experiments showed
that sebaceous gland cells expressed nicotinic acetylcholine recep-
tor-7 (nAchRa7) and acetylcholine enhanced lipid synthesis in a
dose-dependent manner. When sebaceous gland cells were cultured
in the presence of a competitive cholinergic receptor inhibitor,
acetylcholine no longer upregulated lipid synthesis.
The above studies demonstrate that changes in specific sebum
components play important roles in the development of acne.55,56
LI ET AL.
4 | RESEARCH OUTLOOK FOR ACNE
OCCURRENCE MECHANISMS—LIPIDOLOGY
APPLICATIONS
Lipids are essential organic molecules for organisms. With the dis-
covery of their important biological roles, their relationship to dis-
ease, and the development of genomic, proteomic, and systems
biology approaches, the new research field of lipidomics has formed.
Lipidomics is the comprehensive, systemic analysis and identification
of lipids in organisms, tissues, cells, and molecules. The purpose of
this discipline is to understand the structure and function of lipids,
thereby elucidating the relationships between lipid metabolism and
the physiology and pathology of cells, organs, and the body.57 Cur-
rently, lipidomics has been broadly applied to pharmacological
research and development, molecular pathology, functional genomics,
and many other environmental- and health-related research fields.58
The use of lipidomics in the identification and applications of
biomarkers, in particular, have gained considerable attention. For
example, Decastro et al.59,60 applied lipidological methods to analyze
the structure and distribution of platelet lipids between patients with
non-small-cell lung cancer (NSCLC) and healthy individuals and found
platelet linoleic acid may be a potential biomarker of NSCLC. Wang
et al.61 adopted lipidomics methods to analyze plasma lipid compo-
nents between type II diabetes patients and normal individuals and
found that two phosphatidylcholines and two phos-
phatidylethanolamines could serve as potential biomarkers of type II
diabetes.
The rapid development of lipidomics has also accelerated the
identification of sebum biomarkers. For example, Jeroen et al.62
employed liquid chromatography-tandem mass spectroscopy (LC-
MS/MS) methods to analyze the skin lipid composition of patients
with atopic dermatitis (AD) and healthy individuals and found
increased very short-chain ceramides and fatty acids and decreased
long-chain ceramides and fatty acids in the skin of AD patients. In
addition, the changes were more apparent in lesioned skin regions
than in nonlesioned regions. The levels of these lipids can thus serve
as potential biomarkers of AD. Long-chain ceramides and fatty acids
can maintain the skin barrier, and a decrease in these reduces the
tightness of the skin barrier and results in disruption of the barrier
function of the skin. Further work found decreased very long-chain
fatty acid synthase activity might promote the decrease in long-chain
fatty acid and ceramide levels.63 Therefore, biomarker research not
only benefits the elucidation of the molecular mechanisms of AD,
but it is also significant for the diagnosis and treatment of AD. Cam-
era et al.64 employed lipidomics methods to compare forehead lipids
in adolescent patients with acne and healthy individuals and found
the most significant differences in diacylglycerols. Further work can
elucidate the molecular mechanism of diacylglycerols in the develop-
ment of acne.
Therefore, one can take advantage of the high-resolution, high-
throughput methods of lipidomics to study differences in lipid com-
position in acne-lesioned areas, nonlesioned areas, and healthy skin
to screen for lipid biomarkers of acne. Further research will screen
LI ET AL.
for the effects of different lipids on the barrier function of skin, lipid
synthesis pathways, and inflammatory reactions. In addition, analyses
of the effects of these lipids on the expression levels of key
enzymes in sebaceous gland cells will help elucidate the molecular
mechanism of skin lipids in the course of acne development.
REFERENCES
1. Zouboulis CC, Jourdan E, Picardo M. Acne is an inflammatory dis-
ease and alterations of sebum composition initiate acne lesions. J Eur
Acad Dermatol Venereol. 2014;28:527-532.
2. Collier CN, Harper JC, Cantrell WC, Wang W, Foster KW, Elewski
BE. The prevalence of acne in adults 20 years and older. J Am Acad
Dermatol. 2008;58:56-59.
3. Park SY, Kwon HH, Min S, Yoon JY, Suh DH. Epidemiology and risk
factors of childhood acne in Korea: a cross-sectional community
based study. Clin Exp Dermatol. 2015;40:844-850.
4. Okoro EO, Bulus NG, Zouboulis CC. Study of facial Sebum levels
and follicular red fluorescence in patients with acne vulgaris in Nige-
ria. Dermatology. 2016;232:156-161.
5. Luanduan C, Dinan Z, Yang L, Zheng M. Epidemiological investigations
of 2015 secondary students of acne. Chin Mod Doc. 2011;27:6-7.
6. Jian Z. Investigation and Analysis on the prevalence of acne and the
psychological status of the patients with acne. J Yichun Coll.
2011;33:89-90.
7. Gang L, Yanyang P, Ruhong G. Analysis of performance characteris-
tics of acne vulgaris and severity related factors. J Basic Chin Med.
2015;21:81-85.
8. Makrantonaki E, Ganceviciene R, Zouboulis C. An update on the role
of the sebaceous gland in the pathogenesis of acne. Dermato-endocri-
nol. 2011;3:41-49.
9. Bakry OA, El Shazly RM, El Farargy SM, Kotb D. Role of hormones
and blood lipids in the pathogenesis of acne vulgaris in non-obese,
non-hirsute females. Indian Dermatol Online J. 2014;5:S9-S16.
10. Choi CW, Choi JW, Park KC, Youn SW. Facial sebum affects the
development of acne, especially the distribution of inflammatory
acne. J Eur Acad Dermatol Venereol. 2013;27:301-306.
11. Chen HC, Smith SJ, Bryan T, Elias PM, Farese RV Jr. Leptin modulates
the effects of acyl CoA: diacylglycerol acyltransferase deficiency on
murine fur and sebaceous glands. J Clin Invest. 2002;109:175-181.
12. Deplewski D, Rosenfield RL. Role of hormones in pilosebaceous unit
development. Endocr Rev. 2000;21:363-392.
13. Riyanto P, Subchan P, Lelyana R. Advantage of soybean isoflavone as
antiandrogen on acne vulgaris. Dermato-endocrinol. 2015;7:e1063751.
14. Bilgic O, Dogdu M, Islamoglu GK, Altınyazar C. The relationship
between the second to fourth digit ratio and acne vulgaris. J Eur
Acad Dermatol Venereol. 2014;28:1340-1343.
15. Unal M, Unal GU, Balevi S, Tol H, Uyar M. The second to fourth
digit ratio in acne vulgaris. Pediatr Dermatol. 2015;32:651-655.
16. Eady AE, Ingham E, et al. Propionibacterium acnes-friend or foe? Rev
Med Microbiol. 1994;5:163-173.
17. Iinuma K, Sato T, Akimoto N, et al. Involvement of Propionibacterium
acnes in the augmentation of lipogenesis in hamster sebaceous
glands in vivo and in vitro. J Invest Dermatol. 2009;129:2113-2119.
18. Vowels BR, Yang S, Leyden JJ. Induction of proinflammatory cytoki-
nes by a soluble factor of Propionibacterium acnes: implications for
chronic inflammatory acne. Infect Immun. 1995;63:3158-3165.
19. Jappe U, Ingham E, Henwood J, et al. Propionibacterium acnes and
inflammation in acne;P. acnes has T-cell mitogenic activity. Br J Der-
matol. 2002;146:202-209.
20. Kim J, Ochoa MT, Krutzik SR, et al. Activation of toll-like receptor 2
in acne triggers inflammatory cytokine responses. J Immunol.
2002;169:1535-1541.
| 5
21. Jugeau S, Tenaud I, Knol AC, et al. Induction of toll-like receptors by
Propionibacterium acnes. Br J Dermatol. 2005;153:1105-1113.
22. Wilcox HE, Farrar MD, Cunliffe WJ, Holland KT, Ingham E. Resolu-
tion of inflammatory acne vulgaris may involve regulation of CD4+
T-cell responses to Propionibacterium acnes. Br J Dermatol. 2007;156:
460-465.
23. Hao J, Changyi L, Lu Z, et al. Acne patients frequently associated
with abnormal plasma lipid profile. J Dermatol. 2015;42:296-299.
24. Kim MK, Choi SY, Byun HJ, et al. Comparison of sebum secretion,
skin type, pH in humans with and without acne. Arch Dermatol Res.
2006;298:113-119.
25. Youn SW, Park ES, Lee DH, Park KC. Does facial sebum excretion really
affect the development of acne. Br J Dermatol. 2005;153:919-924.
26. Youn SH, Chong WC, Choi JW, et al. Novel facial cosmetic area’O
zone’shows unique characteristics in sebum excretion and acne
lesion distribution. Skin Res Technol. 2013;20:164-169.
27. Youn SW. The role of facial sebum secretion in acne pathogenesis:-
facts and controversies. Clin Dermatol. 2010;28:8-11.
28. Cui L, Jia Y, Cheng ZW, et al. Advancements in the maintenance of
skin barrier/skin lipid composition and the involvement of metabolic
enzymes. J Cosmet Dermatol. 2016;15:549-558.
29. Smith RN, Braue A, Varigos GA, Mann NJ. The effect of a low glyce-
mic load diet on acne vulgaris and the fatty acid composition of skin
surface triglycerides. J Dermatol Sci. 2008;50:41-52.
30. Ottaviani M, Camera E, Picardo M. Lipid mediators in acne. Media-
tors Inflamm. 2010;2010:111-116.
31. Evgenia M, Ruta G, Christos Z. An update on the role of the seba-
ceous gland in the pathogenesis of acne. Dermato-endocrinol.
2011;3:41-49.
32. Monica O, Theodosis A, Enrica F, et al. Peroxidated squalene
induces the production of inflammatory mediators in HaCaT ker-
atinocytes:a possible role in acne vulgaris. J Invest Dermatol.
2006;126:2430-2437.
33. Akaza N, Akamatsu H, Numata S, et al. Fatty acid compositions of
triglycerides and free fatty acids in sebum depend on amount of
triglycerides, and do not differ in presence or absence of acne vul-
garis. J Dermatol. 2014;41:1069-1076.
34. Park HG, Kothapalli KS, Park WJ, et al. Palmitic acid (16:0) competes
with omega-6 linoleic and omega-3 ɑ-linolenic acids for FADS2
mediated D6-desaturation. Biochim Biophys Acta. 2016;1861:91-97.
35. Pappas A. Epidermal surface lipids. Dermato-endocrinol. 2009;1:72-
76.
36. Drake DR, Brogden KA, Dawson DV, et al. Thematic Review Series:
skin Lipids. Antimicrobial lipids at the skin surface. J Lipid Res.
2008;49:4-11.
37. Georgel P, Crozat K, Lauth X, et al. A toll-like receptor 2-responsive
lipid effector pathway protects mammals against skin infections with
gram-positive bacteria. Infect Immun. 2005;73:4512-4521.
38. Wille JJ, Kydonieus A. Palmitoleic acid isomer(C16:1delta6)in human
skin sebum is effective against gram-positive bacteria. Skin Pharmacol
Appl Skin Physiol. 2003;16:176-187.
39. Pham DM, Boussouira B, Moyal D, Nguyen QL. Oxidization of squa-
lene, a human skin lipid: a new and reliable marker of environmental
pollution studies. Int J Cosmet Sci. 2015;37:357-365.
40. Pappas A, Johnsen S, Liu JC, Eisinger M. Sebum analysis of individu-
als with and without acne. Dermato-endocrinol. 2009;1:157-161.
41. Capitanio B, Lora V, Ludovici M, et al. Modulation of sebum oxida-
tion and interleukin-1a levels associates with clinical improvement of
mild comedonal acne. J Eur Acad Dermatol Venereol. 2014;28:1792-
1797.
42. Downing DT, Stewart ME, Wertz PW, Strauss JS. Essential fatty
acids and acne. J Am Acad Dermatol. 1986;14:221-225.
43. Stewart ME, Greenwood R, Cunliffe WJ, Strauss JS, Downing DT.
Effect of cyproterone acetate-ethinyl estradiol treatment on the
6 |
proportion of linoleic and sebaceic acids in various skin surface lipid
classes. Arch Dermatol Res. 1986;278:481-485.
44. Stewart ME, Wertz PW, Crahek MO, et al. Relationship between
sebum secretion rates and the concentration of linoleate in sebum
and epidermal lipids. Clin Res. 1985;33:684-688.
45. Wertz PW, Miethke MC, Long SA, et al. The composition of the cer-
amides from human stratum corneum and from comedones. J Invest
Dermatol. 1985;84:410-412.
46. Cunliffe WJ, Holland DB, Jeremy A. Comedone formation:etiology,
clinical presentation, and treatment. Clin Dermatol. 2004;22:367-
374.
47. Letawe C, Boone M, Pierard GE. Digital image analysis of the effect
of topically applied linoleic acid on acne microcomedones. Clin Exp
Dermatol. 1998;23:56-58.
48. Namazi MR. Further insight into the pathomechanism of acne by
consid-ering the 5-alpha-reductase inhibitory effect of linoleic acid.
Int J Dermatol. 2004;43:701.
49. Jung JY, Kwon HH, Hong JS, et al. Effect of dietary supplementation
with omega-3 fatty acid and gamma-linolenic acid on acne vulgaris:
a randomised, double-blind, controlled trial. Acta Derm Venereol.
2014;94:521-525.
50. Ferre P. The biology of peroxisome proliferator-activated receptors:
relationship with lipid metabolism and insulin sensitivity. Diabetes.
2004;53:43-50.
51. Zouboulis CC, Holger S, Theodosios A. Zileuton prevents the activa-
tion of the leukotriene pathway and reduces sebaceous lipogenesis.
Exp Dermatol. 2010;19:48-50.
52. Alestas T, Ganceviciene R, Fimmel S, et al. Enzymes involved in the
biosynthesis of leukotriene B4 and prostaglandin E2 are active in
sebaceous glands. J Mol Med. 2006;84:75-87.
53. Iinuma K, Sato T, Akimoto N, et al. Induction of inflammatory reac-
tions by lipopolysaccharide in hamster sebaceous glands and pilose-
baceous units in vivo and in vitro. Exp Dermatol. 2010;19:1107-
1109.
54. Zheng JL, Park SB, Sohn KC, et al. Regulation of lipid production by
acetylcholine signalling in human sebaceous glands. J Dermatol Sci.
2013;72:116-122.
55. Zouboulis CC. Zileuton, a new efficient and safe systemic anti-acne
drug. Dermato-endocrinol. 2009;1:188.
LI ET AL.
56. Ebel P, Imgrund S, Vom Dorp K, et al. Ceramide synthase 4 defi-
ciency in mice causes lipid alterations in sebum and results in alope-
cia. Biochem J. 2014;461:147-158.
57. Han XL, Gross RW. Global analyses of cellular lipidomes directly
from crude extracts of biological samples by ESI mass spectrometry:
a bridge to lipidomics. J Lipid Res. 2003;44:1071-1079.
58. TanXi C, PingSheng L, FuQuan Y, et al. The research advances in the
field of lipidomics. Prog Biochem Biophys. 2010;37:121-128.
59. De CJ, Rodr
ıguez MC, Mart
ınezzorzano VS, et al. Erythrocyte and
platelet phospholipid fatty acids as markers of advanced non-small
cell lung cancer: comparison with serum levels of sialic acid, TPS and
Cyfra 21–1. Cancer Invest. 2008;26:407-418.
60. Castro JD, Rodr
ıguez MC, Mart
ınez-Zorzano VS, Llanillo M,
S
anchezyagu €e J. Platelet linoleic acid is a potential biomarker of
advanced non-small cell lung cancer. Exp Mol Pathol. 2009;87:226-233.
61. Wang C, Kong H, Guan Y, et al. Plasma phospholipid metabolic pro-
filing and biomarkers of type 2 diabetes mellitus based on high-per-
formance liquid chromatography/electrospray mass spectrometry
and multivariate statistical analysis. Anal Chem. 2005;77:4108-4116.
62. Smeden J, Janssens M, Kaye ECJ, et al. The importance of free fatty
acid chain length for the skin barrier function in atopic eczema
patients. Exp Dermatol. 2014;23:45-52.
63. Smeden JV, Boiten WA, Hankemeier T, et al. Combined LC/MS-plat-
form for analysis of all major stratum corneum lipids, and the profil-
ing of skin substitutes. Biochim Biophys Acta. 2014;1841:70-79.
64. Camera E, Ludovici M, Tortorella S, et al. Use of lipidomics to inves-
tigate sebum dysfunction in juvenile acne. J Lipid Res.
2016;57:1051-1058. https://doi.org/10.1194/jlr.M067942.
How to cite this article: Li X, He C, Chen Z, Zhou C, Gan Y,
Jia Y. A review of the role of sebum in the mechanism of
acne pathogenesis. J Cosmet Dermatol. 2017;00:1–6.
https://doi.org/10.1111/jocd.12345