Stimulatory influence of D(-)3-hydroxybutyrate feeding on sympathetic nervous system activity in the rat

To examine the effect of ketone body utilization on sympathetic nervous system (SNS) activity, norepinephrine (NE) turnover was measured in heart and interscapular brown adipose tissue (IBAT) of rats fed diets enriched with D(-)3-hydroxybutyrate (3OHB), the naturally occurring isomer of hydroxybutyrate. Isoenergetic substitution of 3OHB for chow for 4 days increased cardiac [3H]NE turnover (P < .025), with a slightly less marked (P < .06) effect in IBAT. When [3H]NE turnover was measured in rats fed chow diets supplemented with 3OHB or sucrose and compared with that in animals fed chow alone, [3H]NE turnover rates in heart and IBAT were similar in the ketone-supplemented and chow-fed groups. Animals fed the sucrose-supplemented chow displayed lower rates of [3H]NE turnover in IBAT than rates found in those given the 3OHB-containing chow (-36%, P < .025 in IBAT). In addition, the stimulatory effect on SNS activity of a 4-day exposure to a sucrose-enriched diet after 2 days of fasting was significantly enhanced by concomitant ketone ingestion. Fractional NE turnover in IBAT was increased from 9.3% +/- 1.3%/h in control rats to 14.2% +/- 0.9%/h in rats refed with 3OHB (P < .005). These observations indicate that increased ketone body utilization does not suppress SNS activity and may stimulate it in a manner quantitatively similar to that seen with carbohydrate or fat ingestion.