Intestinal PPARgamma signaling is required for sympathetic nervous system activation in response to caloric restriction

Duszka K., Picard A., Ellero-Simatos S., Chen J., Defernez M., Paramalingam E., Pigram A., Vanoaica L., Canlet C., Parini P., Narbad A., Guillou H., Thorens B., Wahli W.. (2016)

Scientific Reports, 6, 36937

Intestinal PPARgamma is known for its role in the prevention of colon cancer and inflammatory diseases. However, little is known on its intestinal metabolic functions. To unveil such roles, we submitted intestinal epithelium-specific PPARgamma knockout mice (iePPARgammaKO) to a two week long 25% caloric restriction. Under this condition, iePPARgammaKO mice retain more fat than their wild type (WT) littermates. To explain this adiposity difference between the two genotypes, we compared liver, skeletal muscle, intestinal lipid trafficking, and the microbiome of iePPARgammaKO and WT animals. None of these seemed to contribute to the adiposity phenotype in the CR iePPARgammaKO mice. Interestingly however, CR iePPARgammaKO mice failed to activate the sympathetic nervous system (SNS) and to increase CR-specific locomotor activity. These mice also showed defective control of lowering their body temperature. We conclude that intestinal epithelium PPARgamma plays an essential role in increasing SNS activity under CR conditions, thereby contributing to energy mobilization when calorie intake is reduced.

Scientific Reports, 6, 36937

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