title: A Non-invasive Method to Assess Hepatic Acetyl-CoA In Vivo.
abstract: Acetyl-coenzyme A (acetyl-CoA) is a critical metabolic signaling molecule that regulates gluconeogenesis, pyruvate oxidation, protein acetylation, and steroid and fatty acid biosynthesis; however, measurements of this metabolite using standard biochemical approaches are technically demanding, and there is currently no method to non-invasively assess hepatic acetyl-CoA content in vivo. To this end, we developed and validated a method to non-invasively detect differences in hepatic acetyl-CoA content in vivo across a 5-fold range of physiological acetyl-CoA concentrations by assessing the turnover of [13C4]β-hydroxybutyrate (β-OHB). Here, we show a strong correlation (R2= 0.86, p < 0.0001) between hepatic acetyl-CoA content and β-OHB turnover in rats with varying degrees of fasting hyperglycemia and insulin resistance. These studies demonstrate that β-OHB turnover can be used as a surrogate to non-invasively assess hepatic acetyl-CoA content, thereby allowing researchers to further elucidate the role of this metabolite in the regulation of hepatic gluconeogenesis and other metabolic processes in vivo.
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Rachel J
authors.initials: RJ
authors.lastname: Perry
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510, USA; Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Peng
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Gary W
authors.initials: GW
authors.lastname: Cline
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Kitt Falk
authors.initials: KF
authors.lastname: Petersen
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510, USA; Cellular & Molecular Physiology, Yale University School of Medicine, New Haven, CT 06510, USA; Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA. Electronic address: gerald.shulman@yale.edu.
authors.forename: Gerald I
authors.initials: GI
authors.lastname: Shulman
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000097:blood / Q000378:metabolism; D000105:Acetyl Coenzyme A / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D005215:Fasting / Q000097:blood; D005247:Feeding Behavior / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D005990:Glycerol / Q000494:pharmacology; D006943:Hyperglycemia / Q000097:blood / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D008099:Liver / Q000378:metabolism*; D008297:Male; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D008954:Models, Biological; D051381:Rats; D013217:Starvation / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007328:Insulin; D000105:Acetyl Coenzyme A; D005947:Glucose; D005990:Glycerol; D020155:3-Hydroxybutyric Acid
keywords: acetyl-CoA; ketone turnover; β-hydroxybutyrate