Hexosamines stimulate leptin production in transgenic mice

Donald A. Mcclain, Thomas Alexander, Robert C. Cooksey, Robert Considine

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Hexosamine flux has been shown to mediate aspects of nutrient sensing in insulin sensitive tissues and has been hypothesized to represent a satiety signal that results in shunting of fuel toward storage as fat. It has been recently reported that in vitro treatment of fat and muscle cells with hexosamines and acute glucosamine infusion in intact rats stimulate leptin secretion. In order to investigate the effects of chronic, physiologic increases in hexosamine flux on leptin we have examined leptin mRNA and serum leptin in mice overexpressing the rate-limiting enzyme for hexosamine synthesis, GFA, in muscle and fat. Increased levels of UDP-N-acetylglucosamine, the principal end-product of the hexosamine pathway were seen in transgenic fat, consistent with the overexpression of GFA. After overnight fasting, the transgenic mice were hyperleptinemic compared to littermate controls (4.5 ± 0.5 ng/ml in transgenic, 2.8 ± 0.2 in control, p = 0.005) despite equal body weights. In the random-fed state, the leptin levels of control mice increased to 4.1 ± 0.5 ng/ml (p = 0.01) whereas the leptin levels in the transgenics did not increase any further (3.7 ± 0.4 ng/ml). Leptin mRNA levels were also increased in transgenic fat (2.7 ± 0.6 in transgenic compared to 0.8 ± 0.2 in control, arbitrary units normalized to actin, p < 0.007). Despite increased leptin, the transgenic animals did not have lower body fat content. We conclude that hexosamine flux in fat regulates leptin synthesis and secretion.

Original languageEnglish
Pages (from-to)1999-2002
Number of pages4
JournalEndocrinology
Volume141
Issue number6
DOIs
StatePublished - 2000

Fingerprint

Hexosamines
Leptin
Transgenic Mice
Fats
Uridine Diphosphate N-Acetylglucosamine
Messenger RNA
Genetically Modified Animals
Glucosamine
Adipocytes
Muscle Cells
Adipose Tissue
Actins
Fasting
Body Weight
Insulin
Food
Muscles

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Hexosamines stimulate leptin production in transgenic mice. / Mcclain, Donald A.; Alexander, Thomas; Cooksey, Robert C.; Considine, Robert.

In: Endocrinology, Vol. 141, No. 6, 2000, p. 1999-2002.

Research output: Contribution to journalArticle

Mcclain, DA, Alexander, T, Cooksey, RC & Considine, R 2000, 'Hexosamines stimulate leptin production in transgenic mice', Endocrinology, vol. 141, no. 6, pp. 1999-2002. https://doi.org/10.1210/en.141.6.1999
Mcclain, Donald A. ; Alexander, Thomas ; Cooksey, Robert C. ; Considine, Robert. / Hexosamines stimulate leptin production in transgenic mice. In: Endocrinology. 2000 ; Vol. 141, No. 6. pp. 1999-2002.
@article{5f40de84b9944854a4bdc7069fd2a3b5,
title = "Hexosamines stimulate leptin production in transgenic mice",
abstract = "Hexosamine flux has been shown to mediate aspects of nutrient sensing in insulin sensitive tissues and has been hypothesized to represent a satiety signal that results in shunting of fuel toward storage as fat. It has been recently reported that in vitro treatment of fat and muscle cells with hexosamines and acute glucosamine infusion in intact rats stimulate leptin secretion. In order to investigate the effects of chronic, physiologic increases in hexosamine flux on leptin we have examined leptin mRNA and serum leptin in mice overexpressing the rate-limiting enzyme for hexosamine synthesis, GFA, in muscle and fat. Increased levels of UDP-N-acetylglucosamine, the principal end-product of the hexosamine pathway were seen in transgenic fat, consistent with the overexpression of GFA. After overnight fasting, the transgenic mice were hyperleptinemic compared to littermate controls (4.5 ± 0.5 ng/ml in transgenic, 2.8 ± 0.2 in control, p = 0.005) despite equal body weights. In the random-fed state, the leptin levels of control mice increased to 4.1 ± 0.5 ng/ml (p = 0.01) whereas the leptin levels in the transgenics did not increase any further (3.7 ± 0.4 ng/ml). Leptin mRNA levels were also increased in transgenic fat (2.7 ± 0.6 in transgenic compared to 0.8 ± 0.2 in control, arbitrary units normalized to actin, p < 0.007). Despite increased leptin, the transgenic animals did not have lower body fat content. We conclude that hexosamine flux in fat regulates leptin synthesis and secretion.",
author = "Mcclain, {Donald A.} and Thomas Alexander and Cooksey, {Robert C.} and Robert Considine",
year = "2000",
doi = "10.1210/en.141.6.1999",
language = "English",
volume = "141",
pages = "1999--2002",
journal = "Endocrinology",
issn = "0013-7227",
publisher = "The Endocrine Society",
number = "6",

}

TY - JOUR

T1 - Hexosamines stimulate leptin production in transgenic mice

AU - Mcclain, Donald A.

AU - Alexander, Thomas

AU - Cooksey, Robert C.

AU - Considine, Robert

PY - 2000

Y1 - 2000

N2 - Hexosamine flux has been shown to mediate aspects of nutrient sensing in insulin sensitive tissues and has been hypothesized to represent a satiety signal that results in shunting of fuel toward storage as fat. It has been recently reported that in vitro treatment of fat and muscle cells with hexosamines and acute glucosamine infusion in intact rats stimulate leptin secretion. In order to investigate the effects of chronic, physiologic increases in hexosamine flux on leptin we have examined leptin mRNA and serum leptin in mice overexpressing the rate-limiting enzyme for hexosamine synthesis, GFA, in muscle and fat. Increased levels of UDP-N-acetylglucosamine, the principal end-product of the hexosamine pathway were seen in transgenic fat, consistent with the overexpression of GFA. After overnight fasting, the transgenic mice were hyperleptinemic compared to littermate controls (4.5 ± 0.5 ng/ml in transgenic, 2.8 ± 0.2 in control, p = 0.005) despite equal body weights. In the random-fed state, the leptin levels of control mice increased to 4.1 ± 0.5 ng/ml (p = 0.01) whereas the leptin levels in the transgenics did not increase any further (3.7 ± 0.4 ng/ml). Leptin mRNA levels were also increased in transgenic fat (2.7 ± 0.6 in transgenic compared to 0.8 ± 0.2 in control, arbitrary units normalized to actin, p < 0.007). Despite increased leptin, the transgenic animals did not have lower body fat content. We conclude that hexosamine flux in fat regulates leptin synthesis and secretion.

AB - Hexosamine flux has been shown to mediate aspects of nutrient sensing in insulin sensitive tissues and has been hypothesized to represent a satiety signal that results in shunting of fuel toward storage as fat. It has been recently reported that in vitro treatment of fat and muscle cells with hexosamines and acute glucosamine infusion in intact rats stimulate leptin secretion. In order to investigate the effects of chronic, physiologic increases in hexosamine flux on leptin we have examined leptin mRNA and serum leptin in mice overexpressing the rate-limiting enzyme for hexosamine synthesis, GFA, in muscle and fat. Increased levels of UDP-N-acetylglucosamine, the principal end-product of the hexosamine pathway were seen in transgenic fat, consistent with the overexpression of GFA. After overnight fasting, the transgenic mice were hyperleptinemic compared to littermate controls (4.5 ± 0.5 ng/ml in transgenic, 2.8 ± 0.2 in control, p = 0.005) despite equal body weights. In the random-fed state, the leptin levels of control mice increased to 4.1 ± 0.5 ng/ml (p = 0.01) whereas the leptin levels in the transgenics did not increase any further (3.7 ± 0.4 ng/ml). Leptin mRNA levels were also increased in transgenic fat (2.7 ± 0.6 in transgenic compared to 0.8 ± 0.2 in control, arbitrary units normalized to actin, p < 0.007). Despite increased leptin, the transgenic animals did not have lower body fat content. We conclude that hexosamine flux in fat regulates leptin synthesis and secretion.

UR - http://www.scopus.com/inward/record.url?scp=0034456222&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034456222&partnerID=8YFLogxK

U2 - 10.1210/en.141.6.1999

DO - 10.1210/en.141.6.1999

M3 - Article

C2 - 10830282

AN - SCOPUS:0034456222

VL - 141

SP - 1999

EP - 2002

JO - Endocrinology

JF - Endocrinology

SN - 0013-7227

IS - 6

ER -