Hormonal
Administration of BHB-Phe (50 mg/kg, IP) suppresses food intake and body weight in obese mice by activating distinct hypothalamic and brainstem neural populations, independent of melanocortin, GLP-1, or GDF15 pathways.
This research identifies a specific metabolite, BHB-Phe, which reduces food intake in obese mice. It works by activating specific brain regions, distinct from other known weight loss pathways. While the pathway is conserved in humans, direct efficacy in humans has not been established. Current BHB supplements do not necessarily provide this specific conjugate in bioavailable forms or doses shown to be effective in mice.
Daily administration of BHB-Phe (50 mg/kg/day, IP) resulted in a durable suppression of daily food intake and, as expected, a concomitant reduction in body weight gain... BHB-Phe-treated mice lost the same amount of weight as pair-fed controls... The effect of BHB-Phe (50 mg/kg, IP) on food intake and body weight was similar in WT or MC4R-KO mice... Exendin-3 did not alter the effect of BHB-Phe on food intake and body weight... the effect of BHB-Phe on feeding and body weight was unaffected by anti-GFRAL antibody administration.
Why this rating
High-quality in vivo mouse data with rigorous controls (KO mice, antagonists, pair-feeding), but lacks human clinical trials.
Source
A secondary β-hydroxybutyrate metabolic pathway linked to energy balance
María Dolores Moya-Garzón et al. · bioRxiv (Cold Spring Harbor Laboratory) · 2024
DOI 10.1101/2024.09.09.612087
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