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Acne vulgaris: The metabolic syndrome of the pilosebaceous follicle
Bodo C. Melnik, MD Clinics in Dermatology Volume 36, Issue 1, Pages (January 2018) DOI: /j.clindermatol Copyright © 2017 Elsevier Inc. Terms and Conditions
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Fig. 1 The mTORC1 family. Acne vulgaris and related mTORC1–driven diseases of civilization. BMI, body mass index; mTORC1, mechanistic target of rapamycin complex 1. Clinics in Dermatology , 29-40DOI: ( /j.clindermatol ) Copyright © 2017 Elsevier Inc. Terms and Conditions
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Fig. 2 mTORC1-driven metabolomics in acne vulgaris. Puberty and Western diet increase insulin/insulin-like growth factor 1 (IGF-1) signaling, which enhances androgen (A) synthesis and androgen receptor (AR) activation as well as activation of the kinase AKT. AKT-mediated phosphorylation and thus inhibition of tuberous sclerosis complex 2 (TSC2) activates mTORC1. Androgens via mTORC2-mediated activation of AKT as well as AR-reduced DEPTOR expression further enhance mTORC1 activation. AKT suppresses FoxO transcription factors that suppress AR, SREBP1 and mTORC1. mTORC1 activates the key lipogenic transcription factor sterol response element binding factor 1 (SREBP1), that induces the expression of acetyl CoA carboxylase (ACC), the rate-limiting enzyme of fatty acid de novo synthesis. SREBP1 also induces the expression of Δ6-desaturase and stearoyl CoA desaturase that generate sapienic acid (C16:1Δ6) and oleic acid (C18:1), respectively. Oleic acid promotes Propionibacterium acnes biofilm formation increasing P acnes lipase activity and free fatty acid release and disturbs follicular keratinization. Free palmitic acid (C16:0) and P acnes-derived lipoteichoic acid via Toll-like receptor 2 (TLR2) stimulation activate the NLRP3 inflammasome promoting T helper cell 17 (Th17 cell-driven inflammation. Replacement of linoleate in acylceramides of infundibular keratinocytes by sapienic acid and palmitic acid disturbs follicular barrier function further enhancing follicular inflammation. IL, interleukin. Clinics in Dermatology , 29-40DOI: ( /j.clindermatol ) Copyright © 2017 Elsevier Inc. Terms and Conditions
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