title: Divergent responses to thermogenic stimuli in BAT and subcutaneous adipose tissue from interleukin 18 and interleukin 18 receptor 1-deficient mice.
abstract: Brown and beige adipocytes recruitment in brown (BAT) or white adipose tissue, mainly in the inguinal fat pad (iWAT), meet the need for temperature adaptation in cold-exposure conditions and protect against obesity in face of hypercaloric diets. Using interleukin18 (Il18) and Il18 receptor 1- knockout (Il18r1-KO) mice, this study aimed to investigate the role of IL18 signaling in BAT and iWAT activation and thermogenesis under both stimuli. Il18-KO, extremely dietary obesity-prone as previously described, failed to develop diet-induced thermogenesis as assessed by BAT and iWAT Ucp1 mRNA levels. Overweight when fed standard chow but not HFD, HFD-fed Il18r1-KO mice exhibited increased iWAT Ucp1 gene expression. Energy expenditure was reduced in pre-obese Il18r1-KO mice and restored upon HFD-challenge. Cold exposure lead to similar results; Il18r1-KO mice were protected against acute body temperature drop, displaying a more brown-like structure, alternative macrophage activation and thermogenic gene expression in iWAT than WT controls. Opposite effects were observed in Il18-KO mice. Thus, Il18 and Il18r1 genetic ablation disparate effects on energy homeostasis are likely mediated by divergent BAT responses to thermogenic stimuli as well as iWAT browning. These results suggest that a more complex receptor-signaling system mediates the IL18 adipose-tissue specific effects in energy expenditure.
authors.affiliation: Department of Physiology/Research Center of Molecular Medicine and Chronic Diseases (CIMUS). University of Santiago de Compostela.|Instituto de Investigación Sanitaria de Santiago de Compostela, Santiago de Compostela, Spain.|CIBER Fisiopatología Obesidad y Nutrición (CB06/03), Instituto de Salud Carlos III (ISCIII), Ministerio de Economía y Competitividad (MINECO), Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Pazos
authors.affiliation: Department of Physiology/Research Center of Molecular Medicine and Chronic Diseases (CIMUS). University of Santiago de Compostela.|Instituto de Investigación Sanitaria de Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Lima
authors.affiliation: Department of Physiology/Research Center of Molecular Medicine and Chronic Diseases (CIMUS). University of Santiago de Compostela.|Instituto de Investigación Sanitaria de Santiago de Compostela, Santiago de Compostela, Spain.|CIBER Fisiopatología Obesidad y Nutrición (CB06/03), Instituto de Salud Carlos III (ISCIII), Ministerio de Economía y Competitividad (MINECO), Spain.
authors.forename: Sulay
authors.initials: S
authors.lastname: Tovar
authors.affiliation: Department of Physiology/Research Center of Molecular Medicine and Chronic Diseases (CIMUS). University of Santiago de Compostela.|Instituto de Investigación Sanitaria de Santiago de Compostela, Santiago de Compostela, Spain.|CIBER Fisiopatología Obesidad y Nutrición (CB06/03), Instituto de Salud Carlos III (ISCIII), Ministerio de Economía y Competitividad (MINECO), Spain.
authors.forename: David
authors.initials: D
authors.lastname: González-Touceda
authors.affiliation: Department of Physiology/Research Center of Molecular Medicine and Chronic Diseases (CIMUS). University of Santiago de Compostela.|Instituto de Investigación Sanitaria de Santiago de Compostela, Santiago de Compostela, Spain.|CIBER Fisiopatología Obesidad y Nutrición (CB06/03), Instituto de Salud Carlos III (ISCIII), Ministerio de Economía y Competitividad (MINECO), Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Diéguez
authors.affiliation: Department of Physiology/Research Center of Molecular Medicine and Chronic Diseases (CIMUS). University of Santiago de Compostela.|Instituto de Investigación Sanitaria de Santiago de Compostela, Santiago de Compostela, Spain.|CIBER Fisiopatología Obesidad y Nutrición (CB06/03), Instituto de Salud Carlos III (ISCIII), Ministerio de Economía y Competitividad (MINECO), Spain.
authors.forename: María C
authors.initials: MC
authors.lastname: García
mesh_terms: D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000473:pathology*; D000818:Animals; D003080:Cold Temperature; D059305:Diet, High-Fat; D004734:Energy Metabolism; D015870:Gene Expression; D020382:Interleukin-18 / Q000008:administration & dosage / Q000172:deficiency*; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D053724:Receptors, Interleukin-18 / Q000172:deficiency*; D050151:Subcutaneous Fat / Q000502:physiology*; D022722:Thermogenesis / Q000235:genetics
chemical_list: D020382:Interleukin-18; D053724:Receptors, Interleukin-18