Hypothalamic neurogenesis is not required for the improved insulin sensitivity following exercise training
- Melissa L. Borg,
- Moyra Lemus,
- Alex Reichenbach,
- Ahrathy Selathurai,
- Brian J. Oldfield,
- Zane B. Andrews and
- Matthew J. Watt
- Corresponding author: Matthew J. Watt, Email:
Neurons within the hypothalamic arcuate nucleus (ARC) are important regulators of energy balance. Recent studies suggest that neurogenesis in the ARC is an important regulator of body mass in response to pharmacological stressors. Regular exercise training improves insulin action and is a primary treatment modality for obesity and type 2 diabetes. We examined whether exercise training causes hypothalamic neurogenesis and whether this contributes to exercise-induced improvements in insulin action. Acute exercise in adult mice induced a pro-neurogenic transcriptional program involving growth factors, cell proliferation and neurogenic regulators in the hypothalamus. Daily exercise training for 7 days increased hypothalamic cell proliferation 3.5-fold above sedentary mice, and exercise-induced cell proliferation was maintained in diet-induced obese mice. Colocalization studies indicated negligible neurogenesis in the ARC of sedentary or exercise-trained mice. Blocking cell proliferation via administration of the mitotic blocker cytosine-1-β-D-arabinofuranoside (AraC) did not affect food intake or body mass in obese mice. While four weeks of exercise training improved whole-body insulin sensitivity compared with sedentary mice, insulin action was not affected by AraC administration. These data suggest that regular exercise training induces significant non-neuronal cell proliferation in the hypothalamus of obese mice, but this proliferation is not required for enhanced insulin action.
- Received November 19, 2013.
- Accepted May 29, 2014.
- © 2014 by the American Diabetes Association.
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