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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
Author(s) -
Svart M.,
Rittig N.,
Pedersen S.B.,
Jessen N.,
Møller N.
Publication year - 2021
Publication title -
diabetic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.474
H-Index - 145
eISSN - 1464-5491
pISSN - 0742-3071
DOI - 10.1111/dme.14385
Subject(s) - lipolysis , endocrinology , medicine , hormone sensitive lipase , lipase , adipose tissue , insulin , endogeny , fatty acid , biology , biochemistry , enzyme
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)