Inhibiting HDAC6 to increase satiety in obesity

Inhibiting the cytoplasmic histone deacetylase HDAC6 in the brain could help treat obesity by re-sensitizing hypothalamic cells to the satiety signaling of leptin, reducing fat mass but not lean mass.

To identify genes involved in hunger sensation and leptin sensitivity, transcriptomic analyses of mouse hypothalmi were conducted in four groups of mice with high fat diet-induced obesity: mice exposed to a leptin sensitizer tool compound that induced satiation signals, preventing food intake and thus producing an unsensed hunger state; pair-fed mice yoked to the first group but exposed to only vehicle, and thus sensing the hunger state; pair-fed mice that experienced hunger signals, but were subsequently treated with the leptin sensitizer; and control mice that received vehicle and could eat freely to satiety. ...