Oral β-hydroxybutyrate increases ketonemia, decreases visceral adipocyte volume and improves serum lipid profile in Wistar rats

Abstract

BackgroundKetosis can be induced in humans and in animals by fasting or dietary interventions, such as ketogenic diets. However, the increasing interest on the ketogenic state has motivated the development of alternative approaches to rapidly increase ketonemia using less drastic interventions. Here, it was tested whether oral intake of a β-hydroxybutyrate (βHB) mineral salt mixture could increase ketonemia in Wistar rats without any other dietary changes, thereby being a useful model to study ketones effects alone on metabolism.MethodsβHB salts were orally administered to provoke elevation in the ketonemia. Effects of this intervention were tested acutely (by gavage) and chronically (4 weeks in drinking water). Acutely, a concomitant glucose overload was used to suppress endogenous ketogenesis and verify whether βHB salts were really absorbed or not. Long-term administration allowed to weekly evaluate the impact on ketonemia, blood glucose and, after 4 weeks, on body weight, visceral fat mass, lipid blood profile, serum lipolysis products and adiponectinemia.ResultsβHB salts increased ketonemia in acute and long-term administrations, improved blood lipid profile by raising HDL-cholesterol concentration and decreasing LDL/HDL ratio, while reduced visceral adipocyte volume. Mean ketonemia correlated positively with HDLc and negatively with adipocyte volume and serum lipolysis products.ConclusionsOral βHB can rapidly increase ketonemia and, therefore, be used as an acute and long-term animal model of ketosis. Long-term treatment points to important beneficial effects of ketone bodies in serum lipid concentrations and visceral fat mass. These results may help to explain the metabolic adaptations following ketogenic diets, such as a better body fat control and a serum lipid profile improvement.

On the Metabolism of Exogenous Ketones in Humans

“…Exogenous ketones drinks are growing in popularity as a method to elevate blood ketone concentrations and mimic a ketogenic diet without the need for dietary changes (Ari et al, 2016 ; Cox et al, 2016 ; Kesl et al, 2016 ; Caminhotto et al, 2017 ; Evans et al, 2017 ). The present study describes the pharmacokinetic and pharmacodynamics properties of ketone ester and salt drinks in humans at rest, and characterizes the effects of a prior meal, which is pertinent to use as a dietary supplement.…”

“…An alternative to the ketogenic diet is consumption of drinks containing exogenous dietary ketones, such as ketone esters (KE) and ketone salts (KS). The metabolic effects of KS ingestion have been reported in rats (Ari et al, 2016 ; Kesl et al, 2016 ; Caminhotto et al, 2017 ), in three extremely ill pediatric patients (Plecko et al, 2002 ; Van Hove et al, 2003 ; Valayannopoulos et al, 2011 ) and in cyclists (O'Malley et al, 2017 ; Rodger et al, 2017 ). However, the concentrations of blood βHB reached were low (<1 mM) and a high amount of salt, consumed as sodium, potassium and/or calcium βHB, was required to achieve ketosis.…”

Loss of GPR109A/HCAR2 induces aging-associated hepatic steatosis

“…GPR109A was first identified as the receptor responsible for the pharmacological actions of niacin, a lipid-lowering drug in clinical use for more than 40 years [9–11]. Beta-hydroxybutyrate, identified presently as the only endogenous agonist of the receptor, has too been demonstrated to have some lipid lowering effects [26]. Interestingly, just as some controversy exists regarding whether GPR109A is expressed in liver or not, reports as to whether the lipid-lowering effects of niacin and beta-hydroxybutyrate stem principally from their interaction with the receptor are too conflicting [27–30].…”

β-Hydroxybutyrate inhibits inflammasome activation to attenuate Alzheimer’s disease pathology

“…BHB was administered in drinking water at a final concentration of 0.01875 g/ml. The BHB dose was estimated using previous studies which showed effective ketosis induction without causing side effects [ 22 , 53 – 55 ]. The Institutional Animal Care and Use Committee at the University of Wisconsin approved all protocols used in this study.…”