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Mol Metab. 2014 Oct 16;4(1):58-63. doi: 10.1016/j.molmet.2014.10.001. eCollection 2015 Jan.

Evidence for a novel functional role of astrocytes in the acute homeostatic response to high-fat diet intake in mice.

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Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, 702 Light Hall, 2213 Garland Ave, Nashville, TN 37232, USA.
Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine, 1161 21st Ave. South, Suite T-1217 MCN, Nashville, TN 37232, USA.
Department of Cancer Biology, Vanderbilt University Medical Center, 691 Preston Research Building, 2220 Pierce Ave, Nashville, TN 37232, USA.



Introduction of a high-fat diet to mice results in a period of voracious feeding, known as hyperphagia, before homeostatic mechanisms prevail to restore energy intake to an isocaloric level. Acute high-fat diet hyperphagia induces astrocyte activation in the rodent hypothalamus, suggesting a potential role of these cells in the homeostatic response to the diet. The objective of this study was to determine physiologic role of astrocytes in the acute homeostatic response to high-fat feeding.


We bred a transgenic mouse model with doxycycline-inducible inhibition of NFkappaB (NFκB) signaling in astrocytes to determine the effect of loss of NFκB-mediated astrocyte activation on acute high-fat hyperphagia. ELISA was used to measure the levels of markers of astrocyte activation, glial-fibrillary acidic protein (GFAP) and S100B, in the medial basal hypothalamus.


Inhibition of NFκB signaling in astrocytes prevented acute high-fat diet-induced astrocyte activation and resulted in a 15% increase in caloric intake (P < 0.01) in the first 24 h after introduction of the diet.


These data reveal a novel homeostatic role for astrocytes in the acute physiologic regulation of food intake in response to high-fat feeding.


Astrocyte; CNS, central nervous system; Food intake; GFAP, glial-fibrillary acidic protein; Glia; HFD, high-fat diet; High-fat diet; Hypothalamus; MBH, medial basal hypothalamus; NFκB, nuclear factor kappa B; Nuclear factor-kappaB

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