Brain glucagon-like peptide 1 signaling controls the onset of high-fat diet-induced insulin resistance, and reduces energy expenditure
(2008) Endocrinology — Vol. 149, n° 10, p. 4768-4777 (2008)
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- Glucagon-like peptide-1 (GLP-1) is a peptide released by the intestine and the brain. We previously demonstrated that brain GLP-1 increases glucose-dependent hyperinsulinemia and insulin-resistance. These two features are major characteristics of the onset of type 2 diabetes. Therefore, we investigated whether blocking brain GLP-1 signaling would prevent high-fat diet (HFD)-induced diabetes in the mouse. Our data show that a one month chronic blockage of brain GLP-1 signaling by Exendin-9 (Ex9), totally prevented hyperinsulinemia and insulin-resistance in HFD mice. Furthermore, food intake was dramatically increased but body weight gain was unchanged, showing that brain GLP-1 controlled energy expenditure. Thermogenesis, glucose utilization, oxygen consumption, carbon dioxide production, muscle glycolytic respiratory index, UCP2 expression in muscle, and basal ambulatory activity were all increased by the Ex9 treatment. Thus we have demonstrated that in response to a high-fat diet, brain GLP-1 signaling induces hyperinsulinemia, insulin resistance, and decreases energy expenditure by reducing metabolic thermogenesis and ambulatory activity.
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Knauf, C., Cani, P., Ait-Belgnaoui, A., Benani, A., Dray, C., Cabou, C., Colom, A., Uldry, M., Rastrelli, S., Sabatier, E., Godet, N., Waget, A., Pénicaud, L., Valet, P., & Burcelin, R. (2008). Brain glucagon-like peptide 1 signaling controls the onset of high-fat diet-induced insulin resistance, and reduces energy expenditure. Endocrinology, 149(10), 4768-4777. https://doi.org/10.1210/en.2008-0180 (Original work published 2008)