Energy balance
Pharmacological inhibition of the postsynaptic scaffolding proteins PSD-95 (via UCCB01-147) and PICK1 (via mPD5) induces sustained weight loss in obese mice primarily through a non-aversive reduction in food intake, with effects persisting for days after treatment cessation.
This research identifies two specific brain proteins (PSD-95 and PICK1) that, when blocked by experimental drugs, cause obese mice to eat less without feeling sick, leading to significant fat loss that lasts for days after the drug is stopped. While not yet available for humans, this suggests a potential future treatment class that avoids the common side effects of current obesity drugs and offers sustained benefits.
We demonstrate that daily subcutaneous injections of UCCB01-147 dose-dependently lower body weight and food intake in DIO mice... These data suggest that both UCCB01-147 and mPD5 lower body weight through a nonaversive reduction in food intake... the weight loss was sustained for ~10 days following treatment cessation.
Why this rating
High-quality animal models with rigorous controls (knockouts, inactive analogs), but results are preclinical (mice).
Source
Targeting postsynaptic glutamate receptor scaffolding proteins PSD-95 and PICK1 for obesity treatment
Nicole Fadahunsi et al. · Science Advances · 2024
DOI 10.1126/sciadv.adg2636
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