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

Abstract

SUMMARY The effects of short-term food deprivation on lipid metabolism are well documented, but little is known about prolonged fasting. This study monitored the kinetics of glycerol (rate of appearance, Ra glycerol) and non-esterified fatty acids (Ra NEFA) in fasting rabbits. Our goals were to determine whether lipolysis is stimulated beyond values seen for short-term fasting, and to characterize the roles of primary (intracellular) and secondary (with transit through the circulation) triacylglycerol/fatty acid cycling (TAG/FA cycling) in regulating fatty acid allocation to oxidation or re-esterification. Ra glycerol (9.62±0.72 to 15.29±0.96 μmol kg–1 min–1) and Ra NEFA (18.05±2.55 to 31.25±1.93 μmol kg–1 min–1) were stimulated during the first 2 days of fasting, but returned to baseline after 4 days. An initial increase in TAG/FA cycling was followed by a reduction below baseline after 6 days without food, with primary and secondary cycling contributing to these responses. We conclude that the classic activation of lipolysis caused by short-term fasting is abolished when food deprivation is prolonged. High rates of re-esterification may become impossible to sustain, and TAG/FA cycling could decrease to reduce its cost to 3% of total energy expenditure. Throughout prolonged fasting, fatty acid metabolism gradually shifts towards increased oxidation and reduced re-esterification. Survival is achieved by pressing fuel selection towards the fatty acid dominance of energy metabolism and by slowing substrate cycles to assist metabolic suppression. However, TAG/FA cycling remains active even after prolonged fasting, suggesting that re-esterification is a crucial mechanism that cannot be stopped without harmful consequences.

Glucose uptake in human brown adipose tissue is impaired upon fasting-induced insulin resistance

“…In subcutaneous WAT, [ 18 F]FDG uptake was increased, which may be explained by an increased triacylglycerol/fatty acid cycling, whereby α-glycerol phosphate, which provides the backbone for esterification of NEFAs, is derived from plasma glucose uptake, as demonstrated previously [35]. The energy required for this process might actually contribute to the increase in energy expenditure that we measured upon fasting [36]. In skeletal muscle, cold-induced glucose uptake was not affected by fasting; these results may indicate that even though cold exposure may not be able to increase glucose clearance under insulin-resistant conditions via BAT, the effect of cold exposure on other glucose-consuming tissues may still be worth exploring as a therapy to boost glucose clearance under insulin-resistant states.…”

Food restriction during pregnancy in rabbits: Effects on hormones and metabolites involved in energy homeostasis and metabolic programming

“…Several authors demonstrated an increase of lipolysis and NEFA concentrations during fasting in non pregnant rabbits (Brecchia et al, 2006;Weber and Reidy, 2012). However, there was no complete food deprivation in our experiment and moreover, the energy balance of the first week of rabbit pregnancy is positive because the requirements for foetal growth are relatively small (Fortun-Lamothe, 2006).…”

Adipose Triglyceride Lipase, Not Hormone-Sensitive Lipase, Is the Primary Lipolytic Enzyme in Fasting Elephant Seals (Mirounga angustirostris)

“…Despite stable whole body lipolysis rates, NEFA increased across the fast (similar to our study), suggesting a possible decrease in re-esterification from early to late lactation (Houser ). Reductions in rates of re-esterification with prolonged fasting have also been reported in rabbits (Weber and Reidy 2012) and are suggested in fasting elephant seal weanlings (Viscarra et al 2012). While re-esterification rates are not known in lactating elephant seals, it seems possible that they may play a role in the uncoupling of whole body lipolysis from plasma NEFA concentrations.…”