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

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 [9,10‐3H]‐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