Astrocytic leptin-receptor knockout mice show partial rescue of leptin resistance in diet-induced obesity

1Pennsington Biomedical Research Center.
Journal of Applied Physiology (Impact Factor: 3.43). 01/2013; 114(6). DOI: 10.1152/japplphysiol.01499.2012
Source: PubMed

ABSTRACT To determine how astrocytic leptin signaling regulates the physiological response of mice to diet-induced obesity (DIO), we performed metabolic analyses and hypothalamic leptin signaling assays on astrocytic leptin receptor knockout (ALKO) mice in which astrocytes lack functional ObR signaling. ALKO mice and wildtype (WT) littermate controls were studied at different stages of DIO, with measurement of body weight, percent fat, metabolic activity, and biochemical parameters. When fed with regular chow, the ALKO mice had similar body weight, percent fat, food intake, heat dissipation, respiratory exchange ratio, and activity as their WT littermates. There was no change in blood concentrations of triglyceride, soluble leptin receptor (sObR), mRNA for leptin and uncoupling protein 1 (UCP1) in adipose tissue, and insulin sensitivity. Unexpectedly, in response to a high fat diet the ALKO mice had attenuated hyperleptinemia and sObR, a lower level of leptin mRNA in subcutaneous fat, and a paradoxical increase of UCP1 mRNA. Thus, ALKO mice did not show the worsening of obesity that occurs with normal WT mice as well as with the neuronal ObR mutation resulting in morbid obesity. The findings are consistent with a competing, counter-regulatory model between neuronal and astrocytic leptin signaling.

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