β3-adrenergic receptor agonist causes acute thermogenic metabolic crisis in ACSS1-K635Q knock-in mice
Chocron ES., Zhang D., Sumawi B., Schell J., Cruz D., Li G.
Animal Study, published in Int J Biol Sci (2026) — summary generated from the PubMed abstract.
Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.
- Level A · Stronger Clinical Evidence
- Level B · Emerging clinical evidence with positive signals
- Level C · Early human research exploring benefits
- Level D · Scientific groundwork from lab and animal studies
- Emerging · Emerging topic under active research
This page is generated from the PubMed record. The Thai description is an automated summary of bibliographic fields and the abstract, not a full translation, and is not medical advice.
- Study type
- Animal Study
- Journal
- Int J Biol Sci (2026)
- Reported sample size
- —
- Source database
- Europe PMC
- PMID
- 41608615
- PMCID
- PMC12836529
- DOI
- 10.7150/ijbs.122643
Abstract (original English)
Mitochondrial Acyl-Coenzyme Synthetase Short Chain Family Member-1 (ACSS1) converts free acetate into acetyl-coenzyme A (acetyl-CoA), regulated, in part, by acetylation at lysine 635 (ACSS1-K635). We challenged our ACSS1 constitutive acetylation mimic knock-in (K635Q) mice by injecting a β3-adrenergic receptor agonist, CL-316243 (CL), to induce a thermogenic response. Strikingly, we show that Acss1 K635Q/K635Q mice exhibit hypothermia and acute metabolic crisis following CL stimulus, as shown by significantly reduced oxygen consumption, carbon dioxide production, respiratory exchange ratio, and heat production. We also observed histological differences in both brown adipose tissue (BAT) and subcutaneous white adipose tissue (WAT), accompanied by altered expression and regulation of lipogenic enzymes and Uncoupling Protein 1 (UCP1) in Acss1 K635Q/K635Q . In contrast to wild-type adipose tissues, Acss1 K635Q/K635Q did not show changes in acetyl-CoA and acetate levels in response to CL, and mitochondria isolated from BAT displayed impaired respiration on palmitate. Lastly, beige adipocytes differentiated ex vivo from Acss1 K635Q/K635Q mice showed altered response to the adenylate cyclase stimulator, forskolin, with unresponsive mitochondria and lipogenic lipid droplets, and lower fatty acid oxidation activity. These results suggest that non-acetylated ACSS1 plays an essential role
What this study does not prove
- • This study does not prove SVF is an approved treatment or a replacement for standard care.
- • This is preclinical work; animal or laboratory results cannot be applied to humans.
Evidence level
Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.
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