Overview
- Researchers reporting in Nature Metabolism identified para-tyramine-O-sulfate (pTOS), a metabolite that surges after python meals and suppresses feeding when given to mice.
- In obese mice, repeated pTOS dosing cut food intake and produced about 9% body-weight loss over 28 days without signs of nausea, muscle loss, reduced activity, or changes in energy expenditure.
- Mechanistic work traced pTOS to gut bacteria metabolizing dietary tyrosine; antibiotic pretreatment in pythons blocked the post-meal spike, and the compound activated hypothalamic neurons tied to appetite control.
- Analyses of human datasets detected low baseline pTOS with modest post-meal rises in most people (roughly two- to five-fold) and one outlier near 25-fold, leaving clinical potential and dosing unanswered.
- The lead team from the University of Colorado Boulder, Stanford, and Baylor formed Arkana Therapeutics, which has initial grant funding to develop synthetic analogs and pursue further preclinical and translational studies.