Neuronal deletion of Lepr elicits diabesity in mice without affecting cold tolerance or fertility

Julie E. McMinn, Shun Mei Liu, Hong Liu, Ioannis Dragatsis, Paula Dietrich, Thomas Ludwig, Carol N. Boozer, Streamson C. Chua

Research output: Contribution to journalArticle

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Abstract

Leptin signaling in the brain regulates energy intake and expenditure. To test the degree of functional neuronal leptin signaling required for the maintenance of body composition, fertility, and cold tolerance, transgenic mice expressing Cre in neurons (CaMKIIα-Cre) were crossed to mice carrying a floxed leptin receptor (Lepr) allele to generate mice with neuron-specific deletion of Lepr in ∼50% (C F/F mice) and ∼75% (C Δ17/F mice) of hypothalamic neurons. Leptin receptor (LEPR)-deficient mice (Δ17/ Δ17) with heat-shock-Cre-mediated global Lepr deletion served as obese controls. At 16 wk, male C F/F, C Δ17/F, and Δ17/Δ17 mice were 13.2 (P < 0.05), 45.0, and 55.9% (P < 0.001) heavier, respectively, than lean controls, whereas females showed 31.6, 68.8, and 160.7% increases in body mass (P < 0.001). Significant increases in total fat mass (CF/F: P < 0.01; C Δ17/F and Δ17/Δ17:P < 0.001 vs. sex-matched, lean controls), and serum leptin concentrations (P < 0.001 vs. controls) were present in proportion to Lepr deletion. Male C Δ17/F mice had significant elevations in basal serum insulin concentrations (P < 0.001 vs. controls) and were glucose intolerant, as measured by glucose tolerance test (AUC P < 0.01 vs. controls). In contrast with previous observations in mice null for LEPR signaling, C F/F and C Δ17/F mice were fertile and cold tolerant. These findings support the hypothesis that body weight, adiposity, serum leptin concentrations, and glucose intolerance are proportional to hypothalamic LEPR deficiency. However, fertility and cold tolerance remain intact unless hypothalamic LEPR deficiency is complete.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume289
Issue number3 52-3
DOIs
StatePublished - Sep 1 2005

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Leptin Receptors
Fertility
Leptin
Neurons
Serum
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Glucose Intolerance
Adiposity
Glucose Tolerance Test
Body Composition
Energy Intake
Energy Metabolism
Transgenic Mice
Area Under Curve
Shock
Hot Temperature
Fats
Alleles
Body Weight
Maintenance

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

Cite this

Neuronal deletion of Lepr elicits diabesity in mice without affecting cold tolerance or fertility. / McMinn, Julie E.; Liu, Shun Mei; Liu, Hong; Dragatsis, Ioannis; Dietrich, Paula; Ludwig, Thomas; Boozer, Carol N.; Chua, Streamson C.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 289, No. 3 52-3, 01.09.2005.

Research output: Contribution to journalArticle

McMinn, Julie E. ; Liu, Shun Mei ; Liu, Hong ; Dragatsis, Ioannis ; Dietrich, Paula ; Ludwig, Thomas ; Boozer, Carol N. ; Chua, Streamson C. / Neuronal deletion of Lepr elicits diabesity in mice without affecting cold tolerance or fertility. In: American Journal of Physiology - Endocrinology and Metabolism. 2005 ; Vol. 289, No. 3 52-3.
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