Biguanides Induce Acute de novo Lipogenesis in Human Primary Sebocytes
Abstract
INTRODUCTION: Acne arises during puberty, in part, due to elevated hormones and growth factors which stimulate de novo lipogenesis (DNL) in primary sebocytes to significantly increase sebum production. Oral isotretinoin is an effective acne therapy, reducing sebum production through inducing apoptosis in sebocytes. However, isotretinoin is teratogenic and has additional unwanted side effects, including an initial acne flare-up, which limits its utility. The biguanide, metformin has been found to alleviate severe acne in women with polycystic ovary syndrome (PCOS) through normalization of their insulin and androgen hormone levels. Metformin's broader effectiveness to improve acne in non-PCOS populations lacks significant clinical support. In an effort to determine whether biguanides directly affect sebogenesis, we investigated their ability to alter DNL in cell-based assays in vitro.
METHODS: De novo lipogenesis was measured in human primary sebocytes using [14C]-acetate labeling. Lipid species analysis was performed by extracting newly synthesized lipids and subjecting them to thin layer chromatography. Gene expression changes in sebocytes were identified through qPCR analysis of isolated RNA. Metabolic parameters including oxygen consumption rate, lactate production and activation of adenosine monophosphate-dependent protein kinase (AMPK) were assessed in human primary sebocytes.
RESULTS: Using human primary sebocytes, we found that biguanides, isotretinoin and azithromycin…
Read the paper
Related studies
- Increased expression of circulating miRNA-93 in women with polycystic ovary syndrome may represent a novel, non-invasive biomarker for diagnosis
- Identification of key genes associated with polycystic ovary syndrome (PCOS) and ovarian cancer using an integrated bioinformatics analysis
- Identification of key pathways and genes in polycystic ovary syndrome via integrated bioinformatics analysis and prediction of small therapeutic molecules
- Regulation of Androgen Receptor Expression Alters AMPK Phosphorylation in the Endometrium: In Vivo and In Vitro Studies in Women with Polycystic Ovary Syndrome
- Effect of oral administration of low-dose follicle stimulating hormone on hyperandrogenized mice as a model of polycystic ovary syndrome
- Systems pharmacology to investigate the interaction of berberine and other drugs in treating polycystic ovary syndrome
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.