title: Leptin signal transduction underlies the differential metabolic response of LEW and WKY rats to cafeteria diet.
abstract: Although the effect of genetic background on obesity-related phenotypes is well established, the main objective of this study is to determine the phenotypic responses to cafeteria diet (CAF) of two genetically distinct inbred rat strains and give insight into the molecular mechanisms that might be underlying. Lewis (LEW) and Wistar-Kyoto (WKY) rats were fed with either a standard or a CAF diet. The effects of the diet and the strain in the body weight gain, food intake, respiratory quotient, biochemical parameters in plasma as well as in the expression of genes that regulate leptin signalling were determined. Whereas CAF diet promoted weight gain in LEW and WKY rats, as consequence of increased energy intake, metabolic management of this energy surplus was significantly affected by genetic background. LEW and WKY showed a different metabolic profile, LEW rats showed hyperglycaemia, hypertriglyceridemia and high FFA levels, ketogenesis, high adiposity index and inflammation, but WKY did not. Leptin signalling, and specifically the LepRb-mediated regulation of STAT3 activation and Socs3 gene expression in the hypothalamus were inversely modulated by the CAF diet in LEW (upregulated) and WKY rats (downregulated). In the present study, we show evidence of gene-environment interactions in obesity exerted by differential phenotypic responses to CAF diet between LEW and WKY rats. Specifically, we found the leptin-signalling pathway as a divergent point between the strain-specific adaptations to diet.
authors.affiliation: MoBioFood Research Group. Department of Biochemistry and BiotechnologyUniversitat Rovira i Virgili, Campus Sescelades, C/Marcel.li Domingo, s/n, 43007 Tarragona, SpainImperial College LondonCentre of Complement and Inflammation Research, Du Cane Road, London W12 0NN, UKImperial College LondonMRC Clinical Sciences Centre, Hammersmith Hospital, Du Cane Road, London W12 0NN, UKDuke-NUS Graduate Medical School Singapore8 College Road, 169857 Singapore, Republic of Singapore.
authors.forename: N
authors.initials: N
authors.lastname: Martínez-Micaelo
authors.affiliation: MoBioFood Research Group. Department of Biochemistry and BiotechnologyUniversitat Rovira i Virgili, Campus Sescelades, C/Marcel.li Domingo, s/n, 43007 Tarragona, SpainImperial College LondonCentre of Complement and Inflammation Research, Du Cane Road, London W12 0NN, UKImperial College LondonMRC Clinical Sciences Centre, Hammersmith Hospital, Du Cane Road, London W12 0NN, UKDuke-NUS Graduate Medical School Singapore8 College Road, 169857 Singapore, Republic of Singapore.
authors.forename: N
authors.initials: N
authors.lastname: González-Abuín
authors.affiliation: MoBioFood Research Group. Department of Biochemistry and BiotechnologyUniversitat Rovira i Virgili, Campus Sescelades, C/Marcel.li Domingo, s/n, 43007 Tarragona, SpainImperial College LondonCentre of Complement and Inflammation Research, Du Cane Road, London W12 0NN, UKImperial College LondonMRC Clinical Sciences Centre, Hammersmith Hospital, Du Cane Road, London W12 0NN, UKDuke-NUS Graduate Medical School Singapore8 College Road, 169857 Singapore, Republic of Singapore.
authors.forename: A
authors.initials: A
authors.lastname: Ardévol
authors.affiliation: MoBioFood Research Group. Department of Biochemistry and BiotechnologyUniversitat Rovira i Virgili, Campus Sescelades, C/Marcel.li Domingo, s/n, 43007 Tarragona, SpainImperial College LondonCentre of Complement and Inflammation Research, Du Cane Road, London W12 0NN, UKImperial College LondonMRC Clinical Sciences Centre, Hammersmith Hospital, Du Cane Road, London W12 0NN, UKDuke-NUS Graduate Medical School Singapore8 College Road, 169857 Singapore, Republic of Singapore.
authors.forename: M
authors.initials: M
authors.lastname: Pinent
authors.affiliation: MoBioFood Research Group. Department of Biochemistry and BiotechnologyUniversitat Rovira i Virgili, Campus Sescelades, C/Marcel.li Domingo, s/n, 43007 Tarragona, SpainImperial College LondonCentre of Complement and Inflammation Research, Du Cane Road, London W12 0NN, UKImperial College LondonMRC Clinical Sciences Centre, Hammersmith Hospital, Du Cane Road, London W12 0NN, UKDuke-NUS Graduate Medical School Singapore8 College Road, 169857 Singapore, Republic of Singapore MoBioFood Research Group. Department of Biochemistry and BiotechnologyUniversitat Rovira i Virgili, Campus Sescelades, C/Marcel.li Domingo, s/n, 43007 Tarragona, SpainImperial College LondonCentre of Complement and Inflammation Research, Du Cane Road, London W12 0NN, UKImperial College LondonMRC Clinical Sciences Centre, Hammersmith Hospital, Du Cane Road, London W12 0NN, UKDuke-NUS Graduate Medical School Singapore8 College Road, 169857 Singapore, Republic of Singapore.
authors.forename: E
authors.initials: E
authors.lastname: Petretto
authors.affiliation: MoBioFood Research Group. Department of Biochemistry and BiotechnologyUniversitat Rovira i Virgili, Campus Sescelades, C/Marcel.li Domingo, s/n, 43007 Tarragona, SpainImperial College LondonCentre of Complement and Inflammation Research, Du Cane Road, London W12 0NN, UKImperial College LondonMRC Clinical Sciences Centre, Hammersmith Hospital, Du Cane Road, London W12 0NN, UKDuke-NUS Graduate Medical School Singapore8 College Road, 169857 Singapore, Republic of Singapore mteresa.blay@urv.cat jacques.behmoaras@csc.mrc.ac.uk.
authors.forename: J
authors.initials: J
authors.lastname: Behmoaras
authors.affiliation: MoBioFood Research Group. Department of Biochemistry and BiotechnologyUniversitat Rovira i Virgili, Campus Sescelades, C/Marcel.li Domingo, s/n, 43007 Tarragona, SpainImperial College LondonCentre of Complement and Inflammation Research, Du Cane Road, London W12 0NN, UKImperial College LondonMRC Clinical Sciences Centre, Hammersmith Hospital, Du Cane Road, London W12 0NN, UKDuke-NUS Graduate Medical School Singapore8 College Road, 169857 Singapore, Republic of Singapore mteresa.blay@urv.cat jacques.behmoaras@csc.mrc.ac.uk.
authors.forename: M
authors.initials: M
authors.lastname: Blay
mesh_terms: D050154:Adiposity; D000818:Animals; D004032:Diet; D004435:Eating; D004734:Energy Metabolism; D057140:Fast Foods / Q000009:adverse effects*; D059647:Gene-Environment Interaction; D005838:Genotype; D020738:Leptin / Q000502:physiology*; D008297:Male; D009765:Obesity / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D009929:Organ Size; D011917:Rats, Inbred Lew; D011921:Rats, Inbred WKY; D015398:Signal Transduction; D015430:Weight Gain
chemical_list: D020738:Leptin
keywords: LEW; SOCS3; WKY; cafeteria diet; inbred rats; leptin signalling