High density lipoproteins improve insulin sensitivity in high-fat diet-fed mice by suppressing hepatic inflammation

Obesity-induced liver inflammation can drive insulin resistance. HDL has anti-inflammatory properties, so we hypothesized that low levels of HDL would perpetuate inflammatory responses in the liver and that HDL treatment would suppress liver inflammation and insulin resistance. The aim of this study was to investigate the effects of lipid-free apoAI on hepatic inflammation and insulin resistance in mice. We also investigated apoAI as a component of reconstituted HDLs (rHDLs) in hepatocytes to confirm results we observed in vivo. To test our hypothesis, C57BL/6 mice were fed a high-fat diet (HFD) for 16 weeks and administered either saline or lipid-free apoAI. Injections of lipid-free apoAI twice a week for 2 or 4 weeks with lipid-free apoAI resulted in: i) improved insulin sensitivity associated with decreased systemic and hepatic inflammation; ii) suppression of hepatic mRNA expression for key transcriptional regulators of lipogenic gene expression; and iii) suppression of nuclear factor κB (NF-κB) activation. Human hepatoma HuH-7 cells exposed to rHDLs showed suppressed TNFα-induced NF-κB activation, correlating with decreased NF-κB target gene expression. We conclude that apoAI suppresses liver inflammation in HFD mice and improves insulin resistance via a mechanism that involves a downregulation of NF-κB activation. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc

The use of tandem yeast and mammalian cell in vitro androgen bioassays to detect androgens in internet-sourced sport supplements

Copyright © 2016 John Wiley & Sons, Ltd. Sport supplements containing steroids never approved for therapeutic use have the potential for abuse by athletes. Most are marketed online and may contain undisclosed steroids yet are readily available despite lacking toxicological or pharmacological evaluation. In this study, 18 supplements purchased online underwent organic solvent extraction to isolate any steroids they contained. From the 18 supplements, 19 steroids were identified and for each, its intrinsic androgenic potency was determined by a yeast cell (Saccharomyces cerevisiae) androgen bioassay and its potential androgenic potency was determined by a liver (HuH7) cell androgen bioassay. The yeast bioassay showed that of the 19 steroids tested, 6 demonstrated strong intrinsic bioactivity, with 4 metabolically activated to even stronger androgens. Moreover, 4 steroids with moderate and 1 with intrinsically weak androgenic bioactivity were activated to more potent androgens. Finally, 8 steroids were metabolically inactivated or deactivated into weaker androgens. Our results show that Internet-sourced sport supplements may contain intrinsically strong androgens, or precursors that can be metabolized to them. These potentially potent pharmacologically active steroids are being used without regulatory control or consumer awareness of their potential adverse effects. Copyright © 2016 John Wiley & Sons, Ltd

The use of tandem yeast and mammalian cell in vitro androgen bioassays to detect androgens in internet-sourced sport supplements

Sport supplements containing steroids never approved for therapeutic use have the potential for abuse by athletes. Most are marketed online and may contain undisclosed steroids yet are readily available despite lacking toxicological or pharmacological evaluation. In this study, 18 supplements purchased online underwent organic solvent extraction to isolate any steroids they contained. From the 18 supplements, 19 steroids were identified and for each, its intrinsic androgenic potency was determined by a yeast cell (Saccharomyces cerevisiae) androgen bioassay and its potential androgenic potency was determined by a liver (HuH7) cell androgen bioassay. The yeast bioassay showed that of the 19 steroids tested, 6 demonstrated strong intrinsic bioactivity, with 4 metabolically activated to even stronger androgens. Moreover, 4 steroids with moderate and 1 with intrinsically weak androgenic bioactivity were activated to more potent androgens. Finally, 8 steroids were metabolically inactivated or deactivated into weaker androgens. Our results show that Internet-sourced sport supplements may contain intrinsically strong androgens, or precursors that can be metabolized to them. These potentially potent pharmacologically active steroids are being used without regulatory control or consumer awareness of their potential adverse effects