Oral 3‐hydroxybutyrate ingestion decreases endogenous glucose production, lipolysis, and hormone‐sensitive lipase phosphorylation in adipose tissue in men: a human randomized, controlled, crossover trial. Issue 2 (22nd September 2020)

• Record Type: Journal Article
• Authors: Svart, M.; Rittig, N.; Pedersen, S.B.; Jessen, N.; Møller, N.
• Is Part Of: Diabetic medicine. Volume 38:Issue 2(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-09-22
• Subjects: Diabetes -- Periodicals; 616.462
• DOI: 10.1111/dme.14385
• Languages: English
• ISSNs: 0742-3071

Abstract

Abstract: Aims: To test whether oral administration of D/L‐3‐hydroxybutyrate as a sodium salt inhibits lipolysis and intracellular lipid signalling, in particular, hormone‐sensitive lipase, and whether D/L‐3‐hydroxybutyrate alters endogenous glucose production. Methods: We studied six young men in a randomized, controlled, crossover study after ingestion of Na‐D/L‐3‐hydroxybutyrate (hyperketotic condition) or saline (placebo control). We quantified lipolysis and endogenous glucose production using [9, 10‐ 3 H]‐palmitate and [3‐3H]glucose tracers, and adipose tissue biopsies were collected to investigate key lipolytic enzymes. Results: After ingestion, D/L‐3‐hydroxybutyrate increased by more than 2.5 mmol/l, free fatty acid concentrations decreased by >70%, and palmitate rate of appearance was halved. Protein kinase A phosphorylation of perilipin was reduced and hormone‐sensitive lipase 660 phosphorylation in adipose tissue biopsies was 70–80% decreased in the hyperketotic condition and unchanged in the control. Compared to the control, endogenous glucose production was reduced by close to 20% ( P <0.05) after 3‐hydroxybutyrate ingestion. Conclusion: We conclude that oral D/L‐Na‐3‐hydroxybutyrate increases D/L‐3‐hydroxybutyrate concentrations within half an hour, decreases free fatty acid concentrations, lowers lipolysis and endogenous glucose production, and dephosphorylates hormone‐sensitive lipase. Collectively these phenomena may be viewed as an orchestrated feedback loop, controlling endogenous glucose production, lipolysis and ketogenesis. Such effects would be beneficial in insulin‐resistant states. (www.clinicaltrials.gov ID number: NCT02917252)