title: Extending food deprivation reverses the short-term lipolytic response to fasting: role of the triacylglycerol/fatty acid cycle.
abstract: 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, R(a) glycerol) and non-esterified fatty acids (R(a) 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. R(a) glycerol (9.62±0.72 to 15.29±0.96 μmol kg(-1) min(-1)) and R(a) 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.
authors.affiliation: Biology Department, University of Ottawa, 30 Marie Curie, Ottawa, Ontario, Canada K1N 6N5. jmweber@uOttawa.ca
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Weber
authors.forename: Shannon P
authors.initials: SP
authors.lastname: Reidy
mesh_terms: D000818:Animals; D001835:Body Weight; D002153:Calorimetry, Indirect / Q000379:methods; D004734:Energy Metabolism; D005215:Fasting; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005508:Food Deprivation; D005990:Glycerol / Q000378:metabolism; D007700:Kinetics; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry; D008066:Lipolysis; D008297:Male; D009584:Nitrogen / Q000652:urine; D010100:Oxygen / Q000737:chemistry; D011817:Rabbits; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D008055:Lipids; D014280:Triglycerides; D009584:Nitrogen; D005990:Glycerol; D010100:Oxygen