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This pulsatile enhancement is central to maintaining receptor sensitivity and preventing desensitization associated with sustained hormone exposure

What they found: In normal obese mice: AOD-9604 reduced body fat by 21 % vs placebo, hGH by 24 % The AOD-9604 effect was fully dependent on the 3-adrenergic receptor , in knock-out mice no effect The hGH effect was partly independent of 3-AR , in knock-out mice there was still ~10 % fat reduction AOD-9604 did not raise IGF-1 (control level), whereas hGH raised IGF-1 by 80 % No changes in growth, organ weights (except adipose tissue), fasting insulin Why it matters: The study provided the mechanistic basis for AOD-9604 and confirmed the key business hypothesis: it is possible to separate the lipolytic effect of GH from its growth effect

Abbreviations ER endoplasmic reticulum IMM inner mitochondrial membrane GCL glutamate-cysteine ligase GPx glutathione peroxidases GR glutathione reductase Grx Glutaredoxin GS glutathione synthetase GSH reduced glutathione GSSG oxidized glutathione GSH/GSSG ratio between reduced and oxidized glutathione GST glutathione S-transferase MOM mitochondrial outer membrane mtGSH mitochondrial glutathione OGC 2-oxoglutarate carrier ROS reactive oxygen species SLC soluble carrier protein TR thioredoxin reductase Trx Thioredoxin xCT cystine/glutamate antiporter SLC7A11 Footnotes Conflicts of interest J.W

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Advanced Biology, 7 (6), e2200282