title: Characterization of TGF-β expression and signaling profile in the adipose tissue of rats fed with high-fat and energy-restricted diets.
abstract: Transforming growth factor beta (TGF-β) plays an important role in the pathogenesis of obesity, influencing the release of inflammation mediators and promoting remodeling and collagen deposition in the adipose tissue (AT). In this context, this work aims to elucidate whether TGF-β and Smad-dependent or Smad-independent signaling pathways contribute to regional differentiation of AT in high-fat diet (HFD) and energy-restricted (ER) rat models. For this, TGF-β, TGF-β receptors I and II, PAI-1 and GLUT4 mRNA levels were quantified by real-time PCR, and western blotting assays allowed the semiquantification of TGF-β and proteins from Smad3, ERK1/2 and Akt signaling pathways in subcutaneous and visceral (epididymal, retroperitoneal and mesenteric) fat depots from control, HFD and ER-treated rats. HFD was associated to increased levels of TGF-β and PAI-1 mRNA in epididymal and retroperitoneal visceral fat depots, while ER diet induced a reduction of TGF-β mRNA levels in mesenteric, but surprisingly an increase in retroperitoneal fat. Regarding the different signaling pathways, contrarily to what was found for Smad3, activation of ERK1/2 and Akt in response to HFD was detected in all the visceral but not in subcutaneous fat depots. ER-treated rats presented a more heterogeneous signaling response, as well as decreased TGF-β receptors expression, in the different visceral fat depots. In conclusion, subcutaneous and visceral AT respond differently to distinct diet patterns regarding TGF-β expression and activated signaling pathways. Furthermore, the present study points that visceral AT should not be understood as a homogeneous entity since that response also varied in the different fat depots.
authors.affiliation: Department of Experimental Biology, Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-450, Porto, Portugal; Center for Health Technology and Services Research (CINTESIS), Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-450, Porto, Portugal; Laboratory of Immunology, Basic and Clinical Immunology Unit, Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319, Porto, Portugal.
authors.forename: Bernardo
authors.initials: B
authors.lastname: Sousa-Pinto
authors.affiliation: Department of Experimental Biology, Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-450, Porto, Portugal.
authors.forename: Laura
authors.initials: L
authors.lastname: Gonçalves
authors.affiliation: Department of Experimental Biology, Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-450, Porto, Portugal; Instituto de Investigação e Inovação em Saúde (I3S), Rua Alfredo Allen 208, 4200-135, Porto, Portugal.
authors.forename: Adriana R
authors.initials: AR
authors.lastname: Rodrigues
authors.affiliation: Department of Experimental Biology, Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-450, Porto, Portugal; Instituto de Investigação e Inovação em Saúde (I3S), Rua Alfredo Allen 208, 4200-135, Porto, Portugal; Faculty of Biotechnology, Portuguese Catholic University, Rua Arquiteto Lobão Vital, 4202-401, Porto, Portugal; Hospital CUF Porto, Estrada da Circunvalação 14341, 4100-180, Porto, Portugal.
authors.forename: Inês
authors.initials: I
authors.lastname: Tomada
authors.affiliation: Department of Experimental Biology, Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-450, Porto, Portugal; Instituto de Investigação e Inovação em Saúde (I3S), Rua Alfredo Allen 208, 4200-135, Porto, Portugal.
authors.forename: Henrique
authors.initials: H
authors.lastname: Almeida
authors.affiliation: Department of Experimental Biology, Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-450, Porto, Portugal; Instituto de Investigação e Inovação em Saúde (I3S), Rua Alfredo Allen 208, 4200-135, Porto, Portugal.
authors.forename: Delminda
authors.initials: D
authors.lastname: Neves
authors.affiliation: Department of Experimental Biology, Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-450, Porto, Portugal; Instituto de Investigação e Inovação em Saúde (I3S), Rua Alfredo Allen 208, 4200-135, Porto, Portugal; Faculty of Nutrition and Food Sciences, University of Porto, Rua Dr. Roberto Frias, 4200-465, Porto, Portugal. Electronic address: agouveia@med.up.pt.
authors.forename: Alexandra M
authors.initials: AM
authors.lastname: Gouveia
mesh_terms: D050154:Adiposity; D000818:Animals; D018752:Diet, Fat-Restricted; D059305:Diet, High-Fat / Q000009:adverse effects; D004041:Dietary Fats / Q000009:adverse effects; D005395:Fish Oils / Q000627:therapeutic use*; D005786:Gene Expression Regulation; D050152:Intra-Abdominal Fat / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009765:Obesity / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009928:Organ Specificity; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D015398:Signal Transduction; D050151:Subcutaneous Fat / Q000378:metabolism* / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D004041:Dietary Fats; D005395:Fish Oils; D018125:Receptors, Transforming Growth Factor beta; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1; C494920:Akt1 protein, rat; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; C000625843:Tgfbr1 protein, rat; C029310:lard
keywords: Adipose tissue; Energy restriction; High-fat diet; Obesity; Signaling pathways; Transforming growth factor beta