Activation of G protein-coupled receptors by ketone bodies: Clinical implication of the ketogenic diet in metabolic disorders.
Level 5 - mechanism / opinion, no new human data
Narrative review detailing physiological and receptor mechanisms without systematic review methodology or new human data.
PubMed 36339405 · doi:10.3389/fendo.2022.972890
What was done
This review examined the mechanistic role of ketone bodies (specifically β-hydroxybutyrate and acetoacetate) as ligands for G protein-coupled receptors (GPCRs) during ketogenic diets. The authors focused on potential GPCR-mediated effects in metabolic and endocrine disorders, intending to evaluate studies comparing ketogenic diets against isocaloric non-ketogenic diets to separate ketone-specific signaling from weight-loss effects, as well as assessing short-term tolerability and safety.
What was found
The abstract reports no numerical findings or statistical measures. It describes proposed molecular pathways: β-hydroxybutyrate is hypothesized to exert anti-inflammatory actions through GPR109A-mediated inhibition of the NLRP3 inflammasome, while lipid profile modulation is attributed to acetoacetate acting via GPR43 and β-hydroxybutyrate acting via GPR109A on lipolysis.
Why it matters
Clarifying whether ketogenic diets exert clinical effects via specific receptor pathways (like GPR109A and GPR43) rather than solely through caloric deficit could help identify specific therapeutic targets for metabolic and inflammatory conditions.
Limits
The abstract presents purely qualitative mechanistic descriptions with no primary quantitative data, sample sizes, or study selection criteria. Clinical efficacy, long-term safety, and direct translation from receptor mechanisms to patient outcomes are not quantified.
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