Neuronal deletion of Lepr elicits diabesity in mice without affecting cold tolerance or fertility
| Autor: | Streamson C. Chua, Paula Dietrich, Shun Mei Liu, Hong Liu, Carol N. Boozer, Thomas Ludwig, Julie E. McMinn, Ioannis Dragatsis |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Male
medicine.medical_specialty DNA Complementary Pro-Opiomelanocortin Physiology Ratón Endocrinology Diabetes and Metabolism media_common.quotation_subject Transgene Hypothalamus Adipokine Adipose tissue Mice Transgenic Receptors Cell Surface Fertility Biology Diabetes Mellitus Experimental Eating Mice Adipose Tissue Brown Physiology (medical) Internal medicine medicine Animals Neuropeptide Y Obesity Receptor media_common Mice Knockout Neurons Leptin receptor Leptin Body Weight Adaptation Physiological Arginine Vasopressin Cold Temperature Endocrinology Receptors Leptin Female |
| Zdroj: | American Journal of Physiology-Endocrinology and Metabolism. 289:E403-E411 |
| ISSN: | 1522-1555 0193-1849 |
| Popis: | 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 ( C F/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. |
| Databáze: | OpenAIRE |
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