Obesity and elevated plasma leptin concentration in oMT1A-o growth hormone transgenic mice

Anita M. Oberbauer, Jonathan A. Runstadler, James D. Murray, Peter J Havel

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Objective: This study was undertaken to evaluate plasma leptin concentration in the regulatable ovine metallothionein-ovine growth hormone (oMT1a-oGH) transgenic (TG) mouse model of obesity. Research Methods and Procedures: Transgene stimulus (zinc) was provided at 21 days of age to male and female wild-type (WT) and TG mice. Plasma leptin concentrations were measured by radioimmunoassay at 42, 63, 84, and 105 days of age and from inactivated TG mice at 84 and 105 days. Results: WT and TG mice did not differ significantly in plasma leptin concentration at any of the ages examined (42, 63, 84, and 105 days), although females showed consistently higher plasma leptin concentrations than males regardless of genotype throughout the duration of the study. Male and female TG mice in which the transgene was inactivated at 63 days had a 1.5-fold to 3.5-fold increase in plasma leptin concentration over WT mice and continuously activated TG mice at 84 and 105 days of age. The elevated plasma leptin concentration seen in the inactivated TG mice at 84 and 105 days of age reflects the >300% increase in white adipose tissue seen in this model and correlated with all adipose depot weights and overall body lipid at these later ages. When plasma leptin was expressed per gram of total body fat, the leptin adjusted for body lipid was significantly higher in WT mice than either continuously activated TG or activated and then inactivated TG groups. Discussion: The inactivated TG mice in this study had higher plasma leptin levels with increasing total body adiposity, but the relative proportion of circulating leptin, on a total body lipid basis, was reduced when compared with the WT mice. This reduction was also observed in activated TG mice at the older ages. Although the absolute levels of circulating leptin were elevated in the inactivated TG animals, the amount of leptin produced per gram of fat was lowered. With the inactivation of the transgene, the leptin remained depressed after the removal of the elevated growth hormone. This represents a potential explanation for the ensuing hypertrophy of the fat depots and the abnormal phenotypic response of inactivated TG mice to elevated plasma leptin concentrations resulting in the development of obesity.

Original languageEnglish (US)
Pages (from-to)51-58
Number of pages8
JournalObesity Research
Volume9
Issue number1
StatePublished - Jan 2001

Fingerprint

Leptin
leptin
somatotropin
Transgenic Mice
Growth Hormone
obesity
Obesity
genetically modified organisms
mice
body fat
Transgenes
transgenes
Lipids
Sheep
Fats
sheep
White Adipose Tissue
white adipose tissue
transgenic animals
Genetically Modified Animals

Keywords

  • Adipocyte
  • Leptin
  • Preadipocyte

ASJC Scopus subject areas

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

Cite this

Obesity and elevated plasma leptin concentration in oMT1A-o growth hormone transgenic mice. / Oberbauer, Anita M.; Runstadler, Jonathan A.; Murray, James D.; Havel, Peter J.

In: Obesity Research, Vol. 9, No. 1, 01.2001, p. 51-58.

Research output: Contribution to journalArticle

Oberbauer, AM, Runstadler, JA, Murray, JD & Havel, PJ 2001, 'Obesity and elevated plasma leptin concentration in oMT1A-o growth hormone transgenic mice', Obesity Research, vol. 9, no. 1, pp. 51-58.
Oberbauer, Anita M. ; Runstadler, Jonathan A. ; Murray, James D. ; Havel, Peter J. / Obesity and elevated plasma leptin concentration in oMT1A-o growth hormone transgenic mice. In: Obesity Research. 2001 ; Vol. 9, No. 1. pp. 51-58.
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AB - Objective: This study was undertaken to evaluate plasma leptin concentration in the regulatable ovine metallothionein-ovine growth hormone (oMT1a-oGH) transgenic (TG) mouse model of obesity. Research Methods and Procedures: Transgene stimulus (zinc) was provided at 21 days of age to male and female wild-type (WT) and TG mice. Plasma leptin concentrations were measured by radioimmunoassay at 42, 63, 84, and 105 days of age and from inactivated TG mice at 84 and 105 days. Results: WT and TG mice did not differ significantly in plasma leptin concentration at any of the ages examined (42, 63, 84, and 105 days), although females showed consistently higher plasma leptin concentrations than males regardless of genotype throughout the duration of the study. Male and female TG mice in which the transgene was inactivated at 63 days had a 1.5-fold to 3.5-fold increase in plasma leptin concentration over WT mice and continuously activated TG mice at 84 and 105 days of age. The elevated plasma leptin concentration seen in the inactivated TG mice at 84 and 105 days of age reflects the >300% increase in white adipose tissue seen in this model and correlated with all adipose depot weights and overall body lipid at these later ages. When plasma leptin was expressed per gram of total body fat, the leptin adjusted for body lipid was significantly higher in WT mice than either continuously activated TG or activated and then inactivated TG groups. Discussion: The inactivated TG mice in this study had higher plasma leptin levels with increasing total body adiposity, but the relative proportion of circulating leptin, on a total body lipid basis, was reduced when compared with the WT mice. This reduction was also observed in activated TG mice at the older ages. Although the absolute levels of circulating leptin were elevated in the inactivated TG animals, the amount of leptin produced per gram of fat was lowered. With the inactivation of the transgene, the leptin remained depressed after the removal of the elevated growth hormone. This represents a potential explanation for the ensuing hypertrophy of the fat depots and the abnormal phenotypic response of inactivated TG mice to elevated plasma leptin concentrations resulting in the development of obesity.

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