Ablation of leptin signaling to somatotropes: Changes in metabolic factors that cause obesity

Noor Akhter, Angela K. Odle, Melody L. Allensworth-James, Anessa C. Haney, Mohsin M. Syed, Michael A. Cozart, Streamson C. Chua, Jr., Rhonda Kineman, Gwen V. Childs

Research output: Contribution to journalArticle

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Abstract

Mice with somatotrope-specific deletion of the Janus kinase binding site in leptin receptors are GH deficient as young adults and become obese by 6 months of age. This study focused on the metabolic status of young (3-4.5 month old) preobese mutant mice. These mutants had normal body weights, lean body mass, serum leptin, glucose, and triglycerides. Mutant males and females showed significantly higher respiratory quotients (RQ) and lower energy output, resulting from a higher volume of CO2 output and lower volume of O2 consumption. Deletion mutant females were significantly less active than controls; they had higher levels of total serum ghrelin and ate more food. Mutant females also had lower serum insulin and higher glucagon. In contrast, deletion mutant males were not hyperphagic, but they were more active and spent less time sleeping. Adiponectin and resistin, both products of adipocytes, were increased in male and female mutant mice. In addition, mutant males showed an increase in circulating levels of the potent lipogenic hormone, glucose-dependent insulinotropic peptide. Taken together, these results indicate that mutant mice may become obese due to a reduction in lipid oxidation and energy expenditure. This may stem from GH deficiency. Reduced fat oxidation and enhanced insulin sensitivity (in females) are directly related to GH deficiency in mutant mice because GH has been shown by others to increase insulin sensitivity and fat oxidation and reduce carbohydrate oxidation. Gender-dependent alterations in metabolic signals may further exacerbate the future obese phenotype and affect the timing of its onset. Females show a delay in onset of obesity, perhaps because of their low serum insulin, which is lipogenic, whereas young males already have higher levels of the lipogenic hormone, glucose-dependent insulinotropic peptide. These findings signify that leptin signals to somatotropes are vital for the normal metabolic activity needed to optimize body composition.

Original languageEnglish (US)
Pages (from-to)4705-4715
Number of pages11
JournalEndocrinology
Volume153
Issue number10
DOIs
StatePublished - Oct 1 2012

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Leptin
Obesity
Gastric Inhibitory Polypeptide
Serum
Insulin Resistance
Fats
Hormones
Insulin
Resistin
Janus Kinases
Leptin Receptors
Ideal Body Weight
Ghrelin
Adiponectin
Body Composition
Glucagon
Adipocytes
Energy Metabolism
Young Adult
Triglycerides

ASJC Scopus subject areas

  • Endocrinology

Cite this

Akhter, N., Odle, A. K., Allensworth-James, M. L., Haney, A. C., Syed, M. M., Cozart, M. A., ... Childs, G. V. (2012). Ablation of leptin signaling to somatotropes: Changes in metabolic factors that cause obesity. Endocrinology, 153(10), 4705-4715. https://doi.org/10.1210/en.2012-1331

Ablation of leptin signaling to somatotropes : Changes in metabolic factors that cause obesity. / Akhter, Noor; Odle, Angela K.; Allensworth-James, Melody L.; Haney, Anessa C.; Syed, Mohsin M.; Cozart, Michael A.; Chua, Jr., Streamson C.; Kineman, Rhonda; Childs, Gwen V.

In: Endocrinology, Vol. 153, No. 10, 01.10.2012, p. 4705-4715.

Research output: Contribution to journalArticle

Akhter, N, Odle, AK, Allensworth-James, ML, Haney, AC, Syed, MM, Cozart, MA, Chua, Jr., SC, Kineman, R & Childs, GV 2012, 'Ablation of leptin signaling to somatotropes: Changes in metabolic factors that cause obesity', Endocrinology, vol. 153, no. 10, pp. 4705-4715. https://doi.org/10.1210/en.2012-1331
Akhter N, Odle AK, Allensworth-James ML, Haney AC, Syed MM, Cozart MA et al. Ablation of leptin signaling to somatotropes: Changes in metabolic factors that cause obesity. Endocrinology. 2012 Oct 1;153(10):4705-4715. https://doi.org/10.1210/en.2012-1331
Akhter, Noor ; Odle, Angela K. ; Allensworth-James, Melody L. ; Haney, Anessa C. ; Syed, Mohsin M. ; Cozart, Michael A. ; Chua, Jr., Streamson C. ; Kineman, Rhonda ; Childs, Gwen V. / Ablation of leptin signaling to somatotropes : Changes in metabolic factors that cause obesity. In: Endocrinology. 2012 ; Vol. 153, No. 10. pp. 4705-4715.
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