Parenteral and enteral metabolism of anaplerotic triheptanoin in normal rats. II. Effects on lipolysis, glucose production, and liver acyl-CoA profile.
The anaplerotic odd-medium-chain triglyceride triheptanoin is used in clinical trials for the chronic dietary treatment of patients with long-chain fatty acid oxidation disorders. We previously showed (Kinman RP, Kasumov T, Jobbins KA, Thomas KR, Adams JE, Brunengraber LN, Kutz G, Brewer WU, Roe CR, Brunengraber H. Am J Physiol Endocrinol Metab 291: E860-E866, 2006) that the intravenous infusion of triheptanoin increases lipolysis traced by the turnover of glycerol. In this study, we tested whether lipolysis induced by triheptanoin infusion is accompanied by the potentially harmful release of long-chain fatty acids. Rats were infused with heptanoate +/- glycerol or triheptanoin. Intravenous infusion of triheptanoin at 40% of caloric requirement markedly increased glycerol endogenous R(a) but not oleate endogenous R(a). Thus, the activation of lipolysis was balanced by fatty acid reesterification in the same cells. The liver acyl-CoA profile showed the accumulation of intermediates of heptanoate beta-oxidation and C(5)-ketogenesis and a decrease in free CoA but no evidence of metabolic perturbation of liver metabolism such as propionyl overload. Our data suggest that triheptanoin, administered either intravenously or intraduodenally, could be used for intensive care and nutritional support of metabolically decompensated long-chain fatty acid oxidation disorders.
Gu
Lei
L
Department of Nutrition, Case Western Reserve University, Cleveland, Ohio 44106-4954, USA.
Zhang
Guo-Fang
GF
Kombu
Rajan S
RS
Allen
Frederick
F
Kutz
Gerd
G
Brewer
Wolf-Ulrich
WU
Roe
Charles R
CR
Brunengraber
Henri
H
D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000378:metabolism; D000102:Acetyl-CoA C-Acyltransferase / Q000378:metabolism; D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D019748:Carbon-Carbon Double Bond Isomerases / Q000378:metabolism; D004746:Enoyl-CoA Hydratase / Q000378:metabolism; D004750:Enteral Nutrition; D004951:Esterification / Q000502:physiology; D005227:Fatty Acids / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006537:Heptanoates / Q000008:administration & dosage; D007262:Infusions, Intravenous; D008049:Lipase / Q000378:metabolism; D008066:Lipolysis / Q000502:physiology*; D008099:Liver / Q000201:enzymology; D008297:Male; D019998:Racemases and Epimerases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000008:administration & dosage* / Q000378:metabolism
D005227:Fatty Acids; D006537:Heptanoates; D014280:Triglycerides; C038784:fatty acid oxidation complex; C531010:triheptanoin; D015094:3-Hydroxyacyl CoA Dehydrogenases; D000102:Acetyl-CoA C-Acyltransferase; D008049:Lipase; D004746:Enoyl-CoA Hydratase; D019998:Racemases and Epimerases; D019748:Carbon-Carbon Double Bond Isomerases; D005947:Glucose