CELL AND MOLECULAR PHYSIOLOGY Sequential changes in the expression of genes involved in lipid metabolism in adipose tissue and liver in response to fasting M. Palou & T. Priego & J. Sánchez & E. Villegas & A. M. Rodríguez & A. Palou & C. Picó Received: 11 September 2007 / Revised: 27 December 2007 / Accepted: 16 January 2008 / Published online: 21 May 2008 # Springer-Verlag 2008 Abstract The aim of this study was to provide a sequential analysis of the expression patterns of key genes involved in lipid metabolism in white adipose tissue (WAT) and liver and their relationship with blood parameters in response to fasting. Adult male rats were studied under different feeding conditions: feeding state, after 4, 8, or 24 h fasting, and after 3 h refeeding after 8 h fasting. Blood parameters and the expression of genes involved in lipogenesis and lipolysis in WAT and liver were analyzed. mRNA levels of genes involved in lipogenesis in liver (SREBP1c, FAS, and GPAT) had already decreased after 4 h fasting, as well as those of PPARgamma in WAT, whereas the decrease in SREBP1c, FAS, GPAT, and GLUT4 mRNA levels in WAT was observed after 8 h. Concerning lipolytic and fatty-acid- oxidation-related genes, liver PPARalpha, FGF21, CPT1, and PDK4 mRNA levels increased after 8 h fasting and those of ACOX1 after 24 h, and in WAT, ATGL, and CPT1 mRNA levels were greater after 24 h. Three hours refeeding increased the expression levels of PPARgamma in WAT, SREBP1c in both liver and WAT, and GPAT in liver, and decreased the expression levels of PPARalpha, CPT1, and PDK4 in liver. These results give new insight into the different adaptive time course response to fasting in the expression of genes involved in lipid metabolism, thus pointing out the very rapid response of lipogenic genes, particularly in liver, and the later response of lipolytic genes, particularly in WAT. Keywords Metabolism . Lipolysis . Liver . Adipose tissue . Gene expression Introduction Animals undergo different adaptations to face changes in nutrient availability under the habitual food intake/fasting patterns of feeding, allowing the maintenance of energy homeostasis [12, 28]. Higher animals, under fed conditions, preferentially burn carbohydrate to generate ATP, and surplus carbohydrate is converted into fatty acids (FA), which are then stored as triacylglycerides (TG) in the white adipose tissue (WAT). When glucose availability is low during periods of starvation, there is a gradual shift in fuel utilization to almost exclusively fat. Thus, the TG stored in WAT are hydrolyzed to non-esterified (or free) fatty acids (NEFA), which are mobilized into plasma to reach liver where they play a major role in energy production [15, 35]. The maintenance of nutrient homeostasis under feeding/ fasting conditions and the metabolic response to these situations involve hormonal and metabolic adaptations, which are accompanied by changes in gene expression. Both the WAT and the liver play a key role in the maintenance of nutrient homeostasis. FA released from WATare not only the main fuel for mitochondrial oxidation under fasting conditions but have also been identified as Pflugers Arch - Eur J Physiol (2008) 456:825–836 DOI 10.1007/s00424-008-0461-1 M. Palou : T. Priego : J. Sánchez : E. Villegas : A. M. Rodríguez : A. Palou : C. Picó Biología Molecular, Nutrición y Biotecnología (Nutrigenómica), Universidad de las Islas Baleares (UIB), Palma de Mallorca, Spain M. Palou : T. Priego : J. Sánchez : E. Villegas : A. M. Rodríguez : A. Palou : C. Picó CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto Salud Carlos III, Palma de Mallorca, Spain A. Palou (*) Edificio Mateu Orfila, Universidad de las Islas Baleares, Cra. Valldemossa Km 7.5, Palma de Mallorca 07122, Spain e-mail: andreu.palou@uib.es