Progressive alterations in lipid and glucose metabolism during short-term fasting in young adult men

Abstract

Stable isotope tracers and indirect calorimetry were used to evaluate the progressive alterations in lipid and glucose metabolism after 12, 18, 24, 30, 42, 54, and 72 h of fasting in six healthy male volunteers. The rates of appearance (Ra) of glycerol and palmitic acid in plasma doubled from 2.08 +/- 0.22 and 1.63 +/- 0.20 mumol.kg-1 x min-1, respectively, after 12 h to 4.36 +/- 0.36 and 3.26 +/- 0.40 mumol.kg-1 x min-1, respectively, after 72 h of fasting (P < 0.01). Of the total increase in lipid kinetics, 60% occurred between 12 and 24 h of fasting; the greatest interval change occurred between 18 and 24 h of fasting. Glucose Ra and plasma concentration decreased by approximately 25% between 12 h (11.0 +/- 0.4 mumol.kg-1 x min-1 and 5.58 +/- 0.08 mmol/l, respectively) and 72 h (8.3 +/- 0.3 mumol.kg-1 x min-1 and 4.14 +/- 0.10 mmol/l, respectively) of fasting (P < 0.01), but no statistically significant changes occurred between 18 and 24 h of fasting. Plasma insulin decreased by approximately 50% between 12 h (64.6 +/- 12.9 pmol/l) and 72 h (30.1 +/- 7.9 pmol/l) of fasting (P < 0.001). Of the total decline in plasma insulin, 70% occurred within the first 24 h of fasting. These results demonstrate that the mobilization of adipose tissue triglycerides increases markedly between 18 and 24 h of fasting in young adult men. The early alterations in lipid metabolism are associated with a decline in circulating insulin but do not seem to be regulated by changes in glucose kinetics or plasma glucose concentrations.

Feeding, fasting and starvation: factors affecting fuel utilization

“…However, this takes no account of the likelihood that the mechanisms of glucose production alter during the fast, such that gluconeogenesis is the principal source of glucose at 24 h of fasting. Further evidence supporting this comes from the observations by Romijn et al (1990) and Klein et al (1993) that net glucose oxidation approaches zero within the first 24 h of starvation. This apparent paradox has a simple explanation, in that oxidation of glucose produced via gluconeogenesis from amino acids would not appear through whole-body indirect calorimetry as net glucose oxidation, but rather as protein oxidation.…”

“…The time-courses of the changes in glucose and fatty acid metabolism during the early stages of fasting-starvation provide some insight into the possible controlling mechanism. Klein et al (1993) showed a 35% fall in plasma insulin during the first 24 h of fasting with 50-80% increases in the rates of lipolysis. By contrast, there was no change in the rate of glucose production.…”

Regulation of lipid metabolism in adipose tissue

“…Over the next few days of fast amino acid oxidation diminishes as cells such as neurones start using ketones as an alternative fuel provided by NEFA. Stable-isotope turnover studies have demonstrated that maximum change in lipid metabolism occurs between 12 and 24 hours of starvation (Klein et al 1993). Adipose There is net uptake of non-esterified fatty acids (NEFA) by the adipose tissue under the influence of lipoprotein lipase (LPL).…”

Extending food deprivation reverses the short-term lipolytic response to fasting: role of the triacylglycerol/fatty acid cycle

“…When feeding stops, a shift to the predominant use of lipids is essential to avoid the depletion of small carbohydrate reserves and spare structural proteins (McCue, 2010;Weber, 2011). Therefore, lipolysis and the oxidation of non-esterified fatty acid (rate of oxidation, R ox NEFA) are both stimulated, although current information on lipid kinetics during fasting only comes from shortterm studies in humans (Carlson et al, 1994;Elia et al, 1987;Klein et al, 1993;Wolfe et al, 1987b). After 3-4days without feeding, a 2.5-fold increase in lipolytic rate is observed, typically measured as the rate of appearance of glycerol (R a glycerol) or NEFA (R a NEFA).…”