Effects of Trecadrine®, a β3-adrenergic agonist, on leptin secretion, glucose and lipid metabolism in isolated rat adipocytes

M. J. Moreno-Aliaga, J. A. Martínez, Kimber Stanhope, M. P. Fernández-Otero, Peter J Havel

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

OBJECTIVE: Leptin, a hormone produced in adipocytes, is a key signal in the regulation of food intake and energy expenditure. β-Adrenergic agonists have been shown to inhibit leptin gene expression and leptin secretion. The mechanisms underlying the inhibitory effects of β-adrenergic agonists have not been established. In this study, we examined the effects of Trecadrine®, a novel β3-adrenergic agonist, on basal and insulin-stimulated leptin secretion in isolated rat adipocytes. Because insulin-stimulated glucose metabolism is an important regulator of leptin expression and secretion by the adipocytes, the effects of Trecadrine on indices of adipocyte metabolism were also examined. MEASUREMENTS: Isolated adipocytes were incubated with Trecadrine (10-8-10-4 M) in the absence or presence of insulin (1.6 nM). Leptin secretion, glucose utilization, lactate production, glucose incorporation into CO2 and triglyceride, as well as lipolysis (glycerol release) were determined. RESULTS: Trecadrine induced a concentration-dependent inhibition of basal leptin secretion. Trecadrine also decreased insulin-stimulated leptin secretion; however, the effect was not as pronounced as in the absence of insulin. Treatment of adipocytes with Trecadrine increased basal glucose utilization and produced a further increase in insulin-stimulated glucose utilization. Basal lactate production was also increased by Trecadrine; however, the proportion (percentage) of glucose carbon released as lactate was unaffected. In the presence of insulin, absolute lactate production was unaffected by Trecadrine at 96 h. However, the percentage of glucose carbon released as lactate was significantly decreased by insulin treatment, and was further decreased by the co-treatment with Trecadrine. Trecadrine induced a dose-dependent increase of the absolute amount of glucose incorporated into triglyceride. However, the percentage of glucose utilized that was incorporated into triglyceride was unaffected by Trecadrine. Trecadrine did not modify the proportion of glucose utilized that was oxidized to CO2. Trecadrine increased glycerol release after 96 h of treatment. Glycerol release was negatively correlated with leptin secretion. CONCLUSIONS: These results suggest that alterations of glucose metabolism are not directly involved in the effects of β-adrenergic agonists to inhibit leptin expression and secretion. The inverse relationship between leptin secretion and the increase of glycerol levels, which is an index of the activation of cAMP-dependent protein kinases, suggests that activation of the cAMP signaling pathway mediates the inhibitory effects of Trecadrine on leptin gene expression and secretion.

Original languageEnglish (US)
Pages (from-to)912-919
Number of pages8
JournalInternational Journal of Obesity
Volume26
Issue number7
DOIs
StatePublished - 2002

Fingerprint

adrenergic agonists
Adrenergic Agonists
Leptin
leptin
adipocytes
Lipid Metabolism
Adipocytes
lipid metabolism
secretion
Glucose
glucose
rats
insulin
Insulin
lactates
Lactic Acid
glycerol
Glycerol
triacylglycerols
Triglycerides

Keywords

  • β3-adrenoceptor
  • Insulin-mediated glucose metabolism
  • Lactate
  • Leptin
  • Lipogenesis
  • Lipolysis

ASJC Scopus subject areas

  • Food Science
  • Endocrinology
  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Public Health, Environmental and Occupational Health

Cite this

Effects of Trecadrine®, a β3-adrenergic agonist, on leptin secretion, glucose and lipid metabolism in isolated rat adipocytes. / Moreno-Aliaga, M. J.; Martínez, J. A.; Stanhope, Kimber; Fernández-Otero, M. P.; Havel, Peter J.

In: International Journal of Obesity, Vol. 26, No. 7, 2002, p. 912-919.

Research output: Contribution to journalArticle

Moreno-Aliaga, M. J. ; Martínez, J. A. ; Stanhope, Kimber ; Fernández-Otero, M. P. ; Havel, Peter J. / Effects of Trecadrine®, a β3-adrenergic agonist, on leptin secretion, glucose and lipid metabolism in isolated rat adipocytes. In: International Journal of Obesity. 2002 ; Vol. 26, No. 7. pp. 912-919.
@article{aafdc2d80c204ffcae6889b4d1b091aa,
title = "Effects of Trecadrine{\circledR}, a β3-adrenergic agonist, on leptin secretion, glucose and lipid metabolism in isolated rat adipocytes",
abstract = "OBJECTIVE: Leptin, a hormone produced in adipocytes, is a key signal in the regulation of food intake and energy expenditure. β-Adrenergic agonists have been shown to inhibit leptin gene expression and leptin secretion. The mechanisms underlying the inhibitory effects of β-adrenergic agonists have not been established. In this study, we examined the effects of Trecadrine{\circledR}, a novel β3-adrenergic agonist, on basal and insulin-stimulated leptin secretion in isolated rat adipocytes. Because insulin-stimulated glucose metabolism is an important regulator of leptin expression and secretion by the adipocytes, the effects of Trecadrine on indices of adipocyte metabolism were also examined. MEASUREMENTS: Isolated adipocytes were incubated with Trecadrine (10-8-10-4 M) in the absence or presence of insulin (1.6 nM). Leptin secretion, glucose utilization, lactate production, glucose incorporation into CO2 and triglyceride, as well as lipolysis (glycerol release) were determined. RESULTS: Trecadrine induced a concentration-dependent inhibition of basal leptin secretion. Trecadrine also decreased insulin-stimulated leptin secretion; however, the effect was not as pronounced as in the absence of insulin. Treatment of adipocytes with Trecadrine increased basal glucose utilization and produced a further increase in insulin-stimulated glucose utilization. Basal lactate production was also increased by Trecadrine; however, the proportion (percentage) of glucose carbon released as lactate was unaffected. In the presence of insulin, absolute lactate production was unaffected by Trecadrine at 96 h. However, the percentage of glucose carbon released as lactate was significantly decreased by insulin treatment, and was further decreased by the co-treatment with Trecadrine. Trecadrine induced a dose-dependent increase of the absolute amount of glucose incorporated into triglyceride. However, the percentage of glucose utilized that was incorporated into triglyceride was unaffected by Trecadrine. Trecadrine did not modify the proportion of glucose utilized that was oxidized to CO2. Trecadrine increased glycerol release after 96 h of treatment. Glycerol release was negatively correlated with leptin secretion. CONCLUSIONS: These results suggest that alterations of glucose metabolism are not directly involved in the effects of β-adrenergic agonists to inhibit leptin expression and secretion. The inverse relationship between leptin secretion and the increase of glycerol levels, which is an index of the activation of cAMP-dependent protein kinases, suggests that activation of the cAMP signaling pathway mediates the inhibitory effects of Trecadrine on leptin gene expression and secretion.",
keywords = "β3-adrenoceptor, Insulin-mediated glucose metabolism, Lactate, Leptin, Lipogenesis, Lipolysis",
author = "Moreno-Aliaga, {M. J.} and Mart{\'i}nez, {J. A.} and Kimber Stanhope and Fern{\'a}ndez-Otero, {M. P.} and Havel, {Peter J}",
year = "2002",
doi = "10.1038/sj.ijo.0802003",
language = "English (US)",
volume = "26",
pages = "912--919",
journal = "International Journal of Obesity",
issn = "0307-0565",
publisher = "Nature Publishing Group",
number = "7",

}

TY - JOUR

T1 - Effects of Trecadrine®, a β3-adrenergic agonist, on leptin secretion, glucose and lipid metabolism in isolated rat adipocytes

AU - Moreno-Aliaga, M. J.

AU - Martínez, J. A.

AU - Stanhope, Kimber

AU - Fernández-Otero, M. P.

AU - Havel, Peter J

PY - 2002

Y1 - 2002

N2 - OBJECTIVE: Leptin, a hormone produced in adipocytes, is a key signal in the regulation of food intake and energy expenditure. β-Adrenergic agonists have been shown to inhibit leptin gene expression and leptin secretion. The mechanisms underlying the inhibitory effects of β-adrenergic agonists have not been established. In this study, we examined the effects of Trecadrine®, a novel β3-adrenergic agonist, on basal and insulin-stimulated leptin secretion in isolated rat adipocytes. Because insulin-stimulated glucose metabolism is an important regulator of leptin expression and secretion by the adipocytes, the effects of Trecadrine on indices of adipocyte metabolism were also examined. MEASUREMENTS: Isolated adipocytes were incubated with Trecadrine (10-8-10-4 M) in the absence or presence of insulin (1.6 nM). Leptin secretion, glucose utilization, lactate production, glucose incorporation into CO2 and triglyceride, as well as lipolysis (glycerol release) were determined. RESULTS: Trecadrine induced a concentration-dependent inhibition of basal leptin secretion. Trecadrine also decreased insulin-stimulated leptin secretion; however, the effect was not as pronounced as in the absence of insulin. Treatment of adipocytes with Trecadrine increased basal glucose utilization and produced a further increase in insulin-stimulated glucose utilization. Basal lactate production was also increased by Trecadrine; however, the proportion (percentage) of glucose carbon released as lactate was unaffected. In the presence of insulin, absolute lactate production was unaffected by Trecadrine at 96 h. However, the percentage of glucose carbon released as lactate was significantly decreased by insulin treatment, and was further decreased by the co-treatment with Trecadrine. Trecadrine induced a dose-dependent increase of the absolute amount of glucose incorporated into triglyceride. However, the percentage of glucose utilized that was incorporated into triglyceride was unaffected by Trecadrine. Trecadrine did not modify the proportion of glucose utilized that was oxidized to CO2. Trecadrine increased glycerol release after 96 h of treatment. Glycerol release was negatively correlated with leptin secretion. CONCLUSIONS: These results suggest that alterations of glucose metabolism are not directly involved in the effects of β-adrenergic agonists to inhibit leptin expression and secretion. The inverse relationship between leptin secretion and the increase of glycerol levels, which is an index of the activation of cAMP-dependent protein kinases, suggests that activation of the cAMP signaling pathway mediates the inhibitory effects of Trecadrine on leptin gene expression and secretion.

AB - OBJECTIVE: Leptin, a hormone produced in adipocytes, is a key signal in the regulation of food intake and energy expenditure. β-Adrenergic agonists have been shown to inhibit leptin gene expression and leptin secretion. The mechanisms underlying the inhibitory effects of β-adrenergic agonists have not been established. In this study, we examined the effects of Trecadrine®, a novel β3-adrenergic agonist, on basal and insulin-stimulated leptin secretion in isolated rat adipocytes. Because insulin-stimulated glucose metabolism is an important regulator of leptin expression and secretion by the adipocytes, the effects of Trecadrine on indices of adipocyte metabolism were also examined. MEASUREMENTS: Isolated adipocytes were incubated with Trecadrine (10-8-10-4 M) in the absence or presence of insulin (1.6 nM). Leptin secretion, glucose utilization, lactate production, glucose incorporation into CO2 and triglyceride, as well as lipolysis (glycerol release) were determined. RESULTS: Trecadrine induced a concentration-dependent inhibition of basal leptin secretion. Trecadrine also decreased insulin-stimulated leptin secretion; however, the effect was not as pronounced as in the absence of insulin. Treatment of adipocytes with Trecadrine increased basal glucose utilization and produced a further increase in insulin-stimulated glucose utilization. Basal lactate production was also increased by Trecadrine; however, the proportion (percentage) of glucose carbon released as lactate was unaffected. In the presence of insulin, absolute lactate production was unaffected by Trecadrine at 96 h. However, the percentage of glucose carbon released as lactate was significantly decreased by insulin treatment, and was further decreased by the co-treatment with Trecadrine. Trecadrine induced a dose-dependent increase of the absolute amount of glucose incorporated into triglyceride. However, the percentage of glucose utilized that was incorporated into triglyceride was unaffected by Trecadrine. Trecadrine did not modify the proportion of glucose utilized that was oxidized to CO2. Trecadrine increased glycerol release after 96 h of treatment. Glycerol release was negatively correlated with leptin secretion. CONCLUSIONS: These results suggest that alterations of glucose metabolism are not directly involved in the effects of β-adrenergic agonists to inhibit leptin expression and secretion. The inverse relationship between leptin secretion and the increase of glycerol levels, which is an index of the activation of cAMP-dependent protein kinases, suggests that activation of the cAMP signaling pathway mediates the inhibitory effects of Trecadrine on leptin gene expression and secretion.

KW - β3-adrenoceptor

KW - Insulin-mediated glucose metabolism

KW - Lactate

KW - Leptin

KW - Lipogenesis

KW - Lipolysis

UR - http://www.scopus.com/inward/record.url?scp=0036314563&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036314563&partnerID=8YFLogxK

U2 - 10.1038/sj.ijo.0802003

DO - 10.1038/sj.ijo.0802003

M3 - Article

VL - 26

SP - 912

EP - 919

JO - International Journal of Obesity

JF - International Journal of Obesity

SN - 0307-0565

IS - 7

ER -