1. Inhibition of Sebum Production with the Acetyl Coenzyme A Carboxylase Inhibitor Olumacostat Glasaretil 
David W. Hunt, Geoffrey C. Winters, Roger W. Brownsey, Jerzy E. Kulpa, Kathryn L. Gilliland, Diane M. Thiboutot, Hans E. Hofland 
Journal of Investigative Dermatology 
Volume 137, Issue 7, Pages (July 2017)
DOI: /j.jid
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2. Figure 1
TOFA and the TOFA pro-drug OG suppress de novo lipogenesis in primary human sebocytes. Sebocytes were stimulated with insulin plus the LXR agonist T in the presence of increasing concentrations of TOFA (●) or OG (◯) in 0.1% DMSO. After 24 hours, treatment medium was removed, and the test articles were reapplied in labeling medium containing [14C]-acetate. After an additional 16 hours, cells were harvested using trypsin/EDTA. Lipid extracts were prepared, and the amount of [14C]-acetate incorporation was determined by liquid scintillation counting as a measure of de novo fatty acid synthesis. Mean values with standard deviation for three determinations are plotted. M, mol/L; N/S, non-stimulated; OG, olumacostat glasaretil; TOFA, 5-(tetradecyloxy)-2-furoic acid.
Journal of Investigative Dermatology  , DOI: ( /j.jid )
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3. Figure 2
OG inhibits triacylglycerol formation in primary human sebocytes. Cells were grown to confluency and then stimulated with the LXR agonist T plus insulin in the presence of OG at 0, 0.3, 1.0, or 3.0 μmol/L for 5 days. The TrueMass Sebum Panel analysis was used to measure the levels of the different lipid classes present. Means (nanomoles lipid per 109 cells) ± standard deviation for three separate determinations for sebocytes treated with 0.1% DMSO alone (solid bars) or OG at 0.3 (hatched bars), 1.0 (open bars), or 3.0 (cross-hatched bars) μmol/L are indicated. CE, cholesteryl esters; DAG, diacylglycerols; FA, fatty acids; FC, free cholesterol; OG, olumacostat glasaretil; PL, phospholipids; TAG, triacylglycerols; WE, wax esters.
Journal of Investigative Dermatology  , DOI: ( /j.jid )
Copyright © 2017 The Authors Terms and Conditions

4. Figure 3
Fatty acid composition of triacylglycerols in primary human sebocytes inhibited by OG. TrueMass Sebum Panel analysis was used to characterize the effect of OG treatment on fatty acid composition of different lipid classes in primary human sebocytes. The associated acyl chains are presented on the x-axis using standard fatty acid nomenclature. The fatty acid level on the y-axis is given as nanomoles lipid per 109 cells. This system was also used to measure fatty acid composition and concentrations of other lipid families including fatty acids, cholesterol esters/wax esters, and phospholipids, and these data are shown in the Supplementary Materials. M, mol/L; OG, olumacostat glasaretil.
Journal of Investigative Dermatology  , DOI: ( /j.jid )
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5. Figure 4
Topically applied OG reduces Syrian golden hamster sebaceous gland size. OG at 6% or the solvent mixture alone were applied twice daily for 14 days, once daily for 21 days, or twice daily for 21 days onto one ear. Gels containing 1.0% or 7.5% OG were given once daily for 21 days in parallel with placebo gel. (a) Control groups are denoted by open bars (□), and OG treatment groups are indicated by closed bars (■). For each experiment, results (Oil Red O-positive pixels/skin tissue) were normalized to vehicle-treated animals (100%). Representative histological images of hamster ear sebaceous glands after 21 days of twice-daily treatment with (b) control solvent or (c) 6% OG are shown. Tissue cross-sections are shown with the sebaceous gland-dense treatment (ventral) side facing upward. Scale bar = 500 μm. ∗P < 0.05, ∗∗P < OG, olumacostat glasaretil.
Journal of Investigative Dermatology  , DOI: ( /j.jid )
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6. Figure 5
Topical OG treatment produces changes indicative of increased fatty acid oxidation activity in the sebaceous gland-dense region of the hamster ear. Animals (five per group) were treated with vehicle (□) or 6% OG (■) once daily for 1, 4, or 7 days. Levels of (a) acetyl-CoA and (b) free CoA (free CoA plus GS-S-CoA) for each sample were determined using HPLC analysis; (c) the ratio of acetyl-CoA to total free CoA (free CoA plus GS-S-CoA) was calculated from these values. For the different sampling days, results are given as the percentage of levels determined for hamsters treated with solvent mixture. Acetyl-CoA and free CoA levels averaged 28.1 ± 9.4 and 20.8 ± 3.0 nmol/g, respectively, for ear samples obtained from solvent-treated control animals. ∗P < 0.05, ∗∗P < CoA, coenzyme A; GS-S-CoA, glutathione-CoA-disulfide complex; HPLC, high-performance liquid chromatography; OG, olumacostat glasaretil.
Journal of Investigative Dermatology  , DOI: ( /j.jid )
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7. Figure 6
MALDI imaging shows prominent OG signal in pig ear sebaceous glands 4 hours after topical application of OG 4.0% gel. (a) The histological organization of pig ear skin treated with OG gel and stained with hematoxylin and eosin is shown. (b) The MALDI imaging pattern for an ear tissue cross-section prepared from an OG gel-treated ear is provided. The heat map shows the range of signal intensities, with white regions representing areas of highest OG concentration. (c) Superimposition of hematoxylin and eosin and MALDI images from adjacent tissue cross-sections shows the preferential accumulation of OG signal in pig ear sebaceous glands relative to the surrounding dermis. Scale bar = 2.4 mm. MALDI, matrix-assisted laser desorption/ionization; OG, olumacostat glasaretil.
Journal of Investigative Dermatology  , DOI: ( /j.jid )
Copyright © 2017 The Authors Terms and Conditions