Effects of intravenous methyl palmoxirate on the turnover and oxidation of fatty acids in conscious dogs

James W. Bailey, Michael Dennis Jensen, John M. Miles

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Methyl palmoxirate (MP) is a member of a class of hypoglycemic agents that inhibit fatty acid oxidation in vitro. The studies presented here were undertaken to determine the effects of intravenous (IV) MP on tracer-determined rates of fatty acid oxidation and systemic adipose tissue lipolysis in dogs. MP (40 mg/kg) was administered IV to five mongrel dogs using a primed continuous infusion of [1-14C]palmitate to determine palmitate kinetics. Palmitate concentration and rate of appearance decreased rapidly (from 155 ± 25 to 47 ± 6 μmol/L and 2.9 ± 0.5 to 0.9 ± 0.2 μmol·kg-1·min-1, respectively, at 15 minutes, both P < .05). Palmitate oxidation also decreased, from 1.5 ± 0.4 to 0.3 ± 0.1 μmol·kg-1·min-1, P < .05. Oxidative clearance decreased by approximately 50% 90 minutes after MP administration (P < .05). Fractional oxidation of palmitate also decreased by approximately 40% (P < .05). Plasma insulin increased from 45 ± 6 to 240 ± 93 pmol/L at 15 minutes (P < .05). Plasma glucose decreased over the course of study by approximately 20% (P < .05). In summary, MP has a specific inhibitory effect on plasma free fatty acid (FFA) oxidation in dogs, confirming previous in vitro observations in an in vivo model. In addition, it has a potent antilipolytic effect when administered IV, an effect likely mediated by stimulation of insulin secretion. The observation that systemic FFA oxidation was only partially suppressed at this relatively high dose of MP is consistent with previous studies suggesting that MP may exert its major effect in the liver, and may be less potent in extrahepatic tissues.

Original languageEnglish (US)
Pages (from-to)428-431
Number of pages4
JournalMetabolism
Volume40
Issue number4
DOIs
StatePublished - 1991

Fingerprint

Palmitates
Fatty Acids
Dogs
Nonesterified Fatty Acids
Insulin
Lipolysis
methyl 2-tetradecylglycidate
Hypoglycemic Agents
Adipose Tissue
Glucose
Liver
In Vitro Techniques

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Effects of intravenous methyl palmoxirate on the turnover and oxidation of fatty acids in conscious dogs. / Bailey, James W.; Jensen, Michael Dennis; Miles, John M.

In: Metabolism, Vol. 40, No. 4, 1991, p. 428-431.

Research output: Contribution to journalArticle

@article{1bed44eabfd34f5bb5facdff8b4ba3a8,
title = "Effects of intravenous methyl palmoxirate on the turnover and oxidation of fatty acids in conscious dogs",
abstract = "Methyl palmoxirate (MP) is a member of a class of hypoglycemic agents that inhibit fatty acid oxidation in vitro. The studies presented here were undertaken to determine the effects of intravenous (IV) MP on tracer-determined rates of fatty acid oxidation and systemic adipose tissue lipolysis in dogs. MP (40 mg/kg) was administered IV to five mongrel dogs using a primed continuous infusion of [1-14C]palmitate to determine palmitate kinetics. Palmitate concentration and rate of appearance decreased rapidly (from 155 ± 25 to 47 ± 6 μmol/L and 2.9 ± 0.5 to 0.9 ± 0.2 μmol·kg-1·min-1, respectively, at 15 minutes, both P < .05). Palmitate oxidation also decreased, from 1.5 ± 0.4 to 0.3 ± 0.1 μmol·kg-1·min-1, P < .05. Oxidative clearance decreased by approximately 50{\%} 90 minutes after MP administration (P < .05). Fractional oxidation of palmitate also decreased by approximately 40{\%} (P < .05). Plasma insulin increased from 45 ± 6 to 240 ± 93 pmol/L at 15 minutes (P < .05). Plasma glucose decreased over the course of study by approximately 20{\%} (P < .05). In summary, MP has a specific inhibitory effect on plasma free fatty acid (FFA) oxidation in dogs, confirming previous in vitro observations in an in vivo model. In addition, it has a potent antilipolytic effect when administered IV, an effect likely mediated by stimulation of insulin secretion. The observation that systemic FFA oxidation was only partially suppressed at this relatively high dose of MP is consistent with previous studies suggesting that MP may exert its major effect in the liver, and may be less potent in extrahepatic tissues.",
author = "Bailey, {James W.} and Jensen, {Michael Dennis} and Miles, {John M.}",
year = "1991",
doi = "10.1016/0026-0495(91)90155-P",
language = "English (US)",
volume = "40",
pages = "428--431",
journal = "Metabolism: Clinical and Experimental",
issn = "0026-0495",
publisher = "W.B. Saunders Ltd",
number = "4",

}

TY - JOUR

T1 - Effects of intravenous methyl palmoxirate on the turnover and oxidation of fatty acids in conscious dogs

AU - Bailey, James W.

AU - Jensen, Michael Dennis

AU - Miles, John M.

PY - 1991

Y1 - 1991

N2 - Methyl palmoxirate (MP) is a member of a class of hypoglycemic agents that inhibit fatty acid oxidation in vitro. The studies presented here were undertaken to determine the effects of intravenous (IV) MP on tracer-determined rates of fatty acid oxidation and systemic adipose tissue lipolysis in dogs. MP (40 mg/kg) was administered IV to five mongrel dogs using a primed continuous infusion of [1-14C]palmitate to determine palmitate kinetics. Palmitate concentration and rate of appearance decreased rapidly (from 155 ± 25 to 47 ± 6 μmol/L and 2.9 ± 0.5 to 0.9 ± 0.2 μmol·kg-1·min-1, respectively, at 15 minutes, both P < .05). Palmitate oxidation also decreased, from 1.5 ± 0.4 to 0.3 ± 0.1 μmol·kg-1·min-1, P < .05. Oxidative clearance decreased by approximately 50% 90 minutes after MP administration (P < .05). Fractional oxidation of palmitate also decreased by approximately 40% (P < .05). Plasma insulin increased from 45 ± 6 to 240 ± 93 pmol/L at 15 minutes (P < .05). Plasma glucose decreased over the course of study by approximately 20% (P < .05). In summary, MP has a specific inhibitory effect on plasma free fatty acid (FFA) oxidation in dogs, confirming previous in vitro observations in an in vivo model. In addition, it has a potent antilipolytic effect when administered IV, an effect likely mediated by stimulation of insulin secretion. The observation that systemic FFA oxidation was only partially suppressed at this relatively high dose of MP is consistent with previous studies suggesting that MP may exert its major effect in the liver, and may be less potent in extrahepatic tissues.

AB - Methyl palmoxirate (MP) is a member of a class of hypoglycemic agents that inhibit fatty acid oxidation in vitro. The studies presented here were undertaken to determine the effects of intravenous (IV) MP on tracer-determined rates of fatty acid oxidation and systemic adipose tissue lipolysis in dogs. MP (40 mg/kg) was administered IV to five mongrel dogs using a primed continuous infusion of [1-14C]palmitate to determine palmitate kinetics. Palmitate concentration and rate of appearance decreased rapidly (from 155 ± 25 to 47 ± 6 μmol/L and 2.9 ± 0.5 to 0.9 ± 0.2 μmol·kg-1·min-1, respectively, at 15 minutes, both P < .05). Palmitate oxidation also decreased, from 1.5 ± 0.4 to 0.3 ± 0.1 μmol·kg-1·min-1, P < .05. Oxidative clearance decreased by approximately 50% 90 minutes after MP administration (P < .05). Fractional oxidation of palmitate also decreased by approximately 40% (P < .05). Plasma insulin increased from 45 ± 6 to 240 ± 93 pmol/L at 15 minutes (P < .05). Plasma glucose decreased over the course of study by approximately 20% (P < .05). In summary, MP has a specific inhibitory effect on plasma free fatty acid (FFA) oxidation in dogs, confirming previous in vitro observations in an in vivo model. In addition, it has a potent antilipolytic effect when administered IV, an effect likely mediated by stimulation of insulin secretion. The observation that systemic FFA oxidation was only partially suppressed at this relatively high dose of MP is consistent with previous studies suggesting that MP may exert its major effect in the liver, and may be less potent in extrahepatic tissues.

UR - http://www.scopus.com/inward/record.url?scp=0025803899&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025803899&partnerID=8YFLogxK

U2 - 10.1016/0026-0495(91)90155-P

DO - 10.1016/0026-0495(91)90155-P

M3 - Article

C2 - 1901373

AN - SCOPUS:0025803899

VL - 40

SP - 428

EP - 431

JO - Metabolism: Clinical and Experimental

JF - Metabolism: Clinical and Experimental

SN - 0026-0495

IS - 4

ER -