title: Intestinal PPARγ signalling is required for sympathetic nervous system activation in response to caloric restriction.
abstract: Nuclear receptor PPARγ has been proven to affect metabolism in multiple tissues, and has received considerable attention for its involvement in colon cancer and inflammatory disease. However, its role in intestinal metabolism has been largely ignored. To investigate this potential aspect of PPARγ function, we submitted intestinal epithelium-specific PPARγ knockout mice (iePPARγKO) to a two-week period of 25% caloric restriction (CR), following which iePPARγKO mice retained more fat than their wild type littermates. In attempting to explain this discrepancy, we analysed the liver, skeletal muscle, intestinal lipid trafficking, and the microbiome, none of which appeared to contribute to the adiposity phenotype. Interestingly, under conditions of CR, iePPARγKO mice failed to activate their sympathetic nervous system (SNS) and increase CR-specific locomotor activity. These KO mice also manifested a defective control of their body temperature, which was overly reduced. Furthermore, the white adipose tissue of iePPARγKO CR mice showed lower levels of both hormone-sensitive lipase, and its phosphorylated form. This would result from impaired SNS signalling and possibly cause reduced lipolysis. We conclude that intestinal epithelium PPARγ plays an essential role in increasing SNS activity under CR conditions, thereby contributing to energy mobilization during metabolically stressful episodes.
authors.affiliation: Lee Kong Chian School of Medicine, Nanyang Technological University, The Academia, 20 College Road, 169856, Singapore.|Center for Integrative Genomics, University of Lausanne, Genopode, 1015 Lausanne, Switzerland.
authors.forename: Kalina
authors.initials: K
authors.lastname: Duszka
authors.affiliation: Center for Integrative Genomics, University of Lausanne, Genopode, 1015 Lausanne, Switzerland.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Picard
authors.affiliation: Integrative Toxicology and Metabolism, ToxAlim, Research Center in Food Toxicology, National Institute for Agricultural Research (INRA), 180 Chemin de Tournefeuille, 31300 Toulouse, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Ellero-Simatos
authors.affiliation: Lee Kong Chian School of Medicine, Nanyang Technological University, The Academia, 20 College Road, 169856, Singapore.
authors.forename: Jiapeng
authors.initials: J
authors.lastname: Chen
authors.affiliation: Institute of Food Research, Norwich Science Park, Norwich, Norfolk, NR47UA, UK.
authors.forename: Marianne
authors.initials: M
authors.lastname: Defernez
authors.affiliation: Lee Kong Chian School of Medicine, Nanyang Technological University, The Academia, 20 College Road, 169856, Singapore.
authors.forename: Eeswari
authors.initials: E
authors.lastname: Paramalingam
authors.affiliation: Institute of Food Research, Norwich Science Park, Norwich, Norfolk, NR47UA, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Pigram
authors.affiliation: Center for Integrative Genomics, University of Lausanne, Genopode, 1015 Lausanne, Switzerland.
authors.forename: Liviu
authors.initials: L
authors.lastname: Vanoaica
authors.affiliation: INRA, UMR 1331 Toxalim, Research Centre in Food Toxicology, Axiom Platform, 180 chemin de Tournefeuille, 31027 Toulouse Cedex, France.|Toulouse University, INP, Toxalim, UMR 1331, 31027 Toulouse Cedex, France.|MetaToul-MetaboHUB, National Infrastructure of Metabolomics &Fluxomics, 31027 Toulouse Cedex, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Canlet
authors.affiliation: Department of Laboratory Medicine (LABMED), Division of Clinical Chemistry, and Department of Medicine, Metabolism Unit, Karolinska Institutet at Karolinska Universitetssjukhuset Huddinge, SE-14186, Stockholm, Sweden.
authors.forename: Paolo
authors.initials: P
authors.lastname: Parini
authors.affiliation: Institute of Food Research, Norwich Science Park, Norwich, Norfolk, NR47UA, UK.
authors.forename: Arjan
authors.initials: A
authors.lastname: Narbad
authors.affiliation: Integrative Toxicology and Metabolism, ToxAlim, Research Center in Food Toxicology, National Institute for Agricultural Research (INRA), 180 Chemin de Tournefeuille, 31300 Toulouse, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Guillou
authors.affiliation: Lee Kong Chian School of Medicine, Nanyang Technological University, The Academia, 20 College Road, 169856, Singapore.|Center for Integrative Genomics, University of Lausanne, Genopode, 1015 Lausanne, Switzerland.
authors.forename: Bernard
authors.initials: B
authors.lastname: Thorens
authors.affiliation: Lee Kong Chian School of Medicine, Nanyang Technological University, The Academia, 20 College Road, 169856, Singapore.|Center for Integrative Genomics, University of Lausanne, Genopode, 1015 Lausanne, Switzerland.|Integrative Toxicology and Metabolism, ToxAlim, Research Center in Food Toxicology, National Institute for Agricultural Research (INRA), 180 Chemin de Tournefeuille, 31300 Toulouse, France.
authors.forename: Walter
authors.initials: W
authors.lastname: Wahli
mesh_terms: D052436:Adipose Tissue, White / Q000378:metabolism; D050154:Adiposity / Q000502:physiology; D000818:Animals; D031204:Caloric Restriction / Q000379:methods; D007413:Intestinal Mucosa / Q000378:metabolism; D008066:Lipolysis / Q000502:physiology; D008099:Liver / Q000378:metabolism; D008124:Locomotion / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000378:metabolism*
chemical_list: D047495:PPAR gamma