Premium
Potential role of F ox O 1 and m TORC 1 in the pathogenesis of W estern diet‐induced acne
Author(s) -
Melnik Bodo C.,
Zouboulis Christos C.
Publication year - 2013
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.12142
Subject(s) - mtorc1 , foxo1 , lipogenesis , sterol regulatory element binding protein , biology , transcription factor , microbiology and biotechnology , pi3k/akt/mtor pathway , nutrient sensing , cell growth , ampk , endocrinology , medicine , kinase , signal transduction , protein kinase b , protein kinase a , lipid metabolism , biochemistry , gene
Acne in adolescents of developed countries is an epidemic skin disease and has currently been linked to the W estern diet ( WD ). It is the intention of this viewpoint to discuss the possible impact of WD ‐mediated nutrient signalling in the pathogenesis of acne. High glycaemic load and dairy protein consumption both increase insulin/insulin‐like growth factor‐1 ( IGF ‐1) signalling ( IIS ) that is superimposed on elevated IGF ‐1 signalling of puberty. The cell's nutritional status is primarily sensed by the forkhead box transcription factor O 1 ( F ox O 1) and the serine/threonine kinase mammalian target of rapamycin complex 1 (m TORC 1). Increased IIS extrudes F ox O 1 into the cytoplasm, whereas nuclear F ox O 1 suppresses hepatic IGF ‐1 synthesis and thus impairs somatic growth. F ox O 1 attenuates androgen signalling, interacts with regulatory proteins important for sebaceous lipogenesis, regulates the activity of innate and adaptive immunity, antagonizes oxidative stress and most importantly functions as a rheostat of m TORC 1, the master regulator of cell growth, proliferation and metabolic homoeostasis. Thus, F ox O 1 links nutrient availability to m TORC 1‐driven processes: increased protein and lipid synthesis, cell proliferation, cell differentiation including hyperproliferation of acroinfundibular keratinocytes, sebaceous gland hyperplasia, increased sebaceous lipogenesis, insulin resistance and increased body mass index. Enhanced androgen, TNF ‐α and IGF ‐1 signalling due to genetic polymorphisms promoting the risk of acne all converge in m TORC 1 activation, which is further enhanced by nutrient signalling of WD . Deeper insights into the molecular interplay of F ox O 1/m TORC 1‐mediated nutrient signalling are thus of critical importance to understand the impact of WD on the promotion of epidemic acne and more serious m TORC 1‐driven diseases of civilization.