Latest in general acne research (fall 2015)

Insulin and insulin-like growth factor-1 can modulate the phosphoinositide-3-kinase/Akt/FoxO1 pathway in SZ95 sebocytes in vitro.

Mirdamadi Y et al.

August 2015

A recent hypothesis suggests that a high glycaemic load diet-associated increase of insulin-like growth factor-1 (IGF-1) and insulin may promote acne by reducing nuclear localization of the forkhead box-O1 (FoxO1) transcription factor via activation of the phosphoinositide-3-kinase (PI3K)/Akt pathway. Using SZ95 sebocytes as a model, we investigated the effect of the most important insulinotropic western dietary factors, IGF-1 and insulin on acne. SZ95 sebocytes were stimulated with different concentrations of IGF-1 and insulin (0.001, 0.01, 0.1 and 1 M) for 15 to 120 min PI3K inhibitor LY294002 (50 M). Cytoplasmic and nuclear protein expression of p-Akt and p-FoxO1 as well as FoxO transcriptional activity was analysed. In addition, the proliferation and differentiation of sebocytes and their TLR2/4 expression were determined. We found that high concentrations of IGF-1 and insulin differentially stimulate the PI3K/Akt/FoxO1 pathway by an early up-regulation of cytoplasmic p-Akt and delayed up-regulation of p-FoxO1 resulting in FoxO1 shift to the cytoplasm and the reduction of FoxO transcriptional activity, physiological serum concentration had no effect. IGF-1 at concentrations of 0.1 and 1 M significantly reduced proliferation but increased differentiation of sebocytes to a greater extent than insulin (0.1 and 1 M), but up-regulated TLR2/4 expression to comparable extent. These data provide the first in vitro evidence that FoxO1 principally might be involved in the regulation of growth-factor-stimulatory effects on sebaceous lipogenesis and inflammation in the pathological condition of acne. However, the in vivo significance under physiological conditions remains to be elucidated.

Mechanistic target of rapamycin (mTOR) expression is increased in acne patients skin

Monfrecola G, Lembo S, Caiazzo G

October 2015

Our results provide the rst evidence that mTOR gene expression is increased and S6K1 is activated in acne patients, either in involved or non-involved skin, compared to healthy controls, con-rming the role of mTORC1 signalling in acne pathogenesis.This is a preliminary study with a small number of patients that needs to be enlarged and further experiments are in programme to adequately investigate the cascade activated by mTOR. Nonetheless, our data highlighted a possible role for mTOR,through mTORC1, in the complex inammatory scenario of acne and, in absence of dened metabolic disease, such as obesity or ascertained insulin resistance (..)and it seemed to be related to the glucoseinsulin balance (..). Moreover, the increase in P-S6K1 could represent one of the missing rings in the dietacne chain. The evaluation of mTOR - mTORC1 in acne patients affected by obesity or by insulin resistance, as well as its modication during therapy, or its relation to FoxO1, represents next investigative steps.

Western diet-induced imbalances of FoxO1 and mTORC1 signaling promote the sebofollicular inflammasomopathy acne vulgaris

Bodo C. Melnik

October 2015

Western diet has been linked to the pathogenesis of acne vulgaris that is associated with high intake of hyperglycemic carbohydrates, milk, and saturated fats (..). In 2010, I have proposed that nutrient signaling in acne may reduce the nuclear activity of the metabolic transcription factor FoxO1 (..). In 2012, I have suggested that acne may be linked to increased activity of the nutrient- and growth factor sensitive kinase mechanistic target of rapamycin complex 1 (mTORC1) (..). mTORC1 orchestrates protein and lipid biogenesis, cell growth, and proliferation (..). Mirdamadi et al. (..) showed that insulin/IGF-1 signaling downregulates nuclear FoxO1 levels in SZ95 sebocytes. In this issue, Monfrecola et al. (..) provide direct evidence that mTOR expression and mTORC1-S6K1 signaling are upregulated in the skin of acne patients.