Ketone-body production and oxidation in fasting obese humans.

Abstract

A B S T R A C T Rates of plasma acetoacetate and total ketone-body production and oxidation to C02 were determined by an isotope tracer technique in eight obese subjects undergoing progressive starvation. After a brief fast and under conditions of mild ketonemia and minimal ketonuria, rates of acetoacetate and total ketone-body production and oxidation were directly related to the increasing plasma concentration. After a longer fast and with severer ketonemia, acetoacetate and total ketone-body production and oxidation rates were higher but became constant and unrelated to the plasma concentrations. The maximum rates of total ketone-body production and oxidation were about 150 g/24 h and 129 g/24 h, respectively.Although an increased ketone-body production was the primary factor responsible for the hyperketonemia, an imbalance between production and removal of the ketone bodies cannot be excluded. Such an imbalance could account, at least in part, for the developing hyperketonemia and for the lack of relationship between production rates and plasma concentrations.

The effect of short-term fasting on liver and skeletal muscle lipid, glucose, and energy metabolism in healthy women and men

“…Plasma ketone body concentrations were similar throughout the fast ( Fig. 1C ), suggesting that men and women have similar rates of ketogenesis ( 37 ). Similarly, there were no differences in the rates of hepatic oxidative metabolism at the level of the TCA cycle ( Fig.…”

“…Some individuals (women = 6, men = 5) were re-fed a low-fat meal (60% carbohydrate, 25% fat, and 15% protein; women = 567 and men = 667 kcal), and insulin and glucose excursion were assessed. In the 4 h after refeeding, peak insulin was signifi cantly higher in women (46 [37][38][39][40][41][42][43][44][45][46][47] vs. 20 [15][16][17][18][19][20][21][22][23][24][25] U/ml; P = 0.011), whereas peak glucose concentration did not differ between sexes ( P = 0.233). These fi ndings indicated reduced insulin sensitivity in women after short-term fasting.…”

Hepatic Ketogenesis and Gluconeogenesis in Humans

“…Support for this proposal can be obtained from the observations that the maximum rates of total ketone-body utilization (oxidation) and production were achieved at blood concentration of about 2-3 mmol/liter (32,33), a value found in both lean and obese subjects after about 3 days of starvation (1,2,5).…”

The oxidation of glucose, ketone bodies and acetate by the brain of normal and ketonaemic sheep.

“…With regard to the latter, there is a special difficulty in relation to ketone bodies since we infused only [14C]hydroxybutyrate, whereas both hydroxybutyrate and acetoacetate might contribute to oxidation. When we began this work, we assumed that these two ketone bodies were essentially in isotopic equilibrium as had been reported by Bergman et al (1963) Guest & Foster, 1970) in rats, it has been shown that the method used by Bergman et al (1963) for measurement of specific activities of ketones is not well suited for demonstrating an absence of isotopic equilibrium, and absence of such an equilibrium has been shown both in rats (McGarry et al 1970;Bates, 1971) and in man (Reichard, Owen, Haff, Paul & Bortz, 1974). If this were true in the sheep, the specific activity of acetoacetate would be lower than our measured specific activity of 3-hydroxybutyrate, and since the average specific activity of 'total' ketones would be less, the actual fraction of CO2 derived from both ketones would be greater than our estimate.…”