Ten-year experience with pharmacogenetic testing for DPYD in a national cancer center in Italy: Lessons learned on the path to implementation.

Background: Awareness about the importance of implementing DPYD pharmacogenetics in clinical practice to prevent severe side effects related to the use of fluoropyrimidines has been raised over the years. Since 2012 at the National Cancer Institute, CRO-Aviano (Italy), a diagnostic DPYD genotyping service was set up. Purpose: This study aims to describe the evolution of DPYD diagnostic activity at our center over the last 10 years as a case example of a successful introduction of pharmacogenetic testing in clinical practice. Methods: Data related to the diagnostic activity of in-and out-patients referred to our service between January 2012 and December 2022 were retrieved from the hospital database. Results: DPYD diagnostic activity at our center has greatly evolved over the years, shifting gradually from a post-toxicity to a pre-treatment approach. Development of pharmacogenetic guidelines by national and international consortia, genotyping, and IT technology evolution have impacted DPYD testing uptake in the clinics. Our participation in a large prospective implementation study (Ubiquitous Pharmacogenomics) increased health practitioners' and patients' awareness of pharmacogenetic matters and provided additional standardized infrastructures for genotyping and reporting. Nationwide test reimbursement together with recommendations by regulatory agencies in Europe and Italy in 2020 definitely changed the clinical practice guidelines of fluoropyrimidines prescription. A dramatic increase in the number of pre-treatment DPYD genotyping and in the coverage of new fluoropyrimidine prescriptions was noticed by the last year of observation (2022). Conclusion: The long path to a successful DPYD testing implementation in the clinical practice of a National Cancer Center in Italy demonstrated that the development of pharmacogenetic guidelines and genotyping infrastructure standardization as well as capillary training and education activity for all the potential stakeholders are fundamental. However, only national health politics of test reimbursement and clear recommendations by drug regulatory agencies will definitely move the field forward.

Vermian subtentorial arteriovenous malformation supplied by the artery of Wollschlaeger and Wollschlaeger.

BACKGROUND: The artery of Wollschlaeger and Wollschlaeger is a tentorial branch of the superior cerebellar artery: due to its small diameter, it is not usually seen in normal angiograms except when enlarged in the setting of a dural AVF or tentorial meningioma. Its presence has been rarely described in the Literature. CASE REPORT: herein we describe the first ever reported case of a vermian subtentorial arteriovenous malformation supplied by the artery of Wollschlaeger and Wollschlaeger in 70 year old female patient. CONCLUSION: vermian subtentorial AVMs supplied by the artery of Wollschlaeger and Wollschlaeger are extremely rare vascular malformations. The presence of the artery of Wollschlaeger and Wollschlaeger must be carefully evaluated during preoperative surgical planning due to its key role in the supply of vascular malformation and to decrease the risk of intra operative bleeding during surgery.

Frequency shift algorithm: Application to a frequency-domain multiplexing readout of x-ray transition-edge sensor microcalorimeters.

In the frequency-domain multiplexing (FDM) scheme, transition-edge sensors (TESs) are individually coupled to superconducting LC filters and AC biased at MHz frequencies through a common readout line. To make efficient use of the available readout bandwidth and to minimize the effect of non-linearities, the LC resonators are usually designed to be on a regular grid. The lithographic processes, however, pose a limit on the accuracy of the effective filter resonance frequencies. Off-resonance bias carriers could be used to suppress the impact of intermodulation distortions, which, nonetheless, would significantly affect the effective bias circuit and the detector spectral performance. In this paper, we present a frequency shift algorithm (FSA) to allow off-resonance readout of TESs, while preserving the on-resonance bias circuit and spectral performance, demonstrating its application to the FDM readout of an x-ray TES microcalorimeter array. We discuss the benefits in terms of mitigation of the impact of intermodulation distortions at the cost of increased bias voltage and the scalability of the algorithm to multi-pixel FDM readout. We show that with FSA, in the multi-pixel and frequencies shifted on-grid, the line noises due to intermodulation distortion are placed away from the sensitive region in the TES response and the x-ray performance is consistent with the single-pixel, on-resonance level.

Performance and uniformity of a kilo-pixel array of Ti/Au transition-edge sensor microcalorimeters.

Uniform large transition-edge sensor (TES) arrays are fundamental for the next generation of x-ray space observatories. These arrays are required to achieve an energy resolution ΔE < 3 eV full width at half maximum (FWHM) in the soft x-ray energy range. We are currently developing x-ray microcalorimeter arrays for use in the future laboratory and space-based x-ray astrophysics experiments and ground-based spectrometers. In this contribution, we report on the development and the characterization of a uniform 32 × 32 pixel array with 140 × 30 µm2 Ti/Au TESs with the Au x-ray absorber. We report on extensive measurements on 60 pixels in order to show the uniformity of our large TES array. The averaged critical temperature is Tc = 89.5 ± 0.5 mK, and the variation across the array (∼1 cm) is less than 1.5 mK. We found a large region of detector's bias points between 20% and 40% of the normal-state resistance where the energy resolution is constantly lower than 3 eV. In particular, results show a summed x-ray spectral resolution ΔEFWHM = 2.50 ± 0.04 eV at a photon energy of 5.9 keV, measured in a single-pixel mode using a frequency domain multiplexing readout system developed at SRON/VTT at bias frequencies ranging from 1 MHz to 5 MHz. Moreover, we compare the logarithmic resistance sensitivity with respect to temperature and current (α and ß, respectively) and their correlation with the detector's noise parameter M, showing a homogeneous behavior for all the measured pixels in the array.

The problem with implementing fish farms in agricultural regions: A trial in a pampean pond highlights potential risks to both human and fish health.

The safety of creating fish farms in agricultural settings was evaluated by growing Piaractus mesopotamicus in a pond, while crops where cultivated in a nearby field under a pesticide application regime typical of the Pampa region. Atrazine, glyphosate and its metabolite, aminomethylphosphonic acid (AMPA), were detected in the water of the pond at concentrations ranging between 92 and 118 µg/L for atrazine, 12 and 221 µg/L for glyphosate and 21 and 117 µg/L for AMPA. Atrazine and malathion were detected in fish muscles at concentrations ranging between 70 and 105 µg/kg for atrazine and 8.6 and 23.7 µg/kg for malathion. Compared to fish raised in a pisciculture, fish from the agricultural pond presented reduced values of pack cell volume, hemoglobin, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration, together with significantly greater cholinesterase activity in both plasma and liver and reduced glutathione-S-transferase activity in the liver. A comet assay also demonstrated that P. mesopotamicus from the agricultural pond presented a significantly greater level of DNA damage in both erythrocytes and gill cells. Overall, the present study demonstrates that pisciculture ponds established in an agricultural setting may receive pesticides applied to nearby cultures and that these pesticides may be taken up by the fish and affect their physiology and health. The accumulation of pesticides residues in fish flesh may also present a risk to human consumers and should be closely controlled.

Sensitivity analysis of the Pesticide in Water Calculator model for applications in the Pampa region of Argentina.

Despite the widespread use of pesticides in the Pampa region of Argentina, mathematical models are rarely employed to predict pesticide fate due to the lack of regionally tested models and the absence of readily available databases to run such models. The objective of the current study was to perform a sensitivity analysis of the Pesticide in Water Calculator (PWC) model for the Pampa Region of Argentina. The sensitivity analysis was performed while simulating applications of 2,4-D (mobile, low Kd) and glyphosate (soil-binding, high Kd) in five localities of the Pampa region: Anguil, Paraná, Marcos Juárez, Pergamino and Tres Arroyos. The sensitivity of the various parameters involved in PWC modelling was evaluated though a two-steps sensitivity analysis which included a first screening of less sensitive parameters with Morris method, followed by a fully global sensitivity analysis of the remaining parameters using Sobol method. When ran under soil and climate conditions typical of the Pampa region of Argentina, PWC was most sensitive to 25% of the parameters evaluated. The sensitive parameters identified depended mainly on the nature of the pesticide molecule being modelled; the location and endpoint considered having much less influence on the sensitivity results. Sensitive parameters belonged to two main grand categories: (i) degradation rates of the pesticide in soil and water, and (ii) parameters descriptive of soil binding, runoff and erosion. The sensitivity analysis of the model PWC performed in the current study represents a crucial first step towards the development and expansion of probabilistic pesticide risk assessment in Argentina, and provides important parameterization criteria that will help obtaining more certain modelling results from PWC in Argentina and elsewhere.

Genome-wide association study of milk fatty acid composition in Italian Simmental and Italian Holstein cows using single nucleotide polymorphism arrays.

Bovine milk is important for human nutrition, but its fat content is often criticized as a risk factor in cardiovascular disease. Selective breeding programs could be used to alter the fatty acid (FA) composition of bovine milk to improve the healthiness of dairy products for human consumption. Here, we performed a genome-wide association study (GWAS) on bovine milk to identify genomic regions or specific genes associated with FA profile and to investigate genetic differences between the Italian Simmental (IS) and Italian Holstein (IH) breeds. To achieve this, we first characterized milk samples from 416 IS cows and 436 IH cows for their fat profile by gas chromatography. Subjects were genotyped with single nucleotide polymorphism array and a single-marker regression model for GWAS was performed. Our findings confirm previously reported quantitative trait loci strongly associated with bovine milk fat composition. More specifically, our GWAS results revealed significant signals on chromosomes Bos taurus autosome 19 and 26 for milk FA. Further analysis using a gene-centric approach and pathway meta-analysis identified not only some well-known genes underlying quantitative trait loci for milk FA components, such as FASN, SCD, and DGAT1, but also other significant candidate genes, including some with functional roles in pathways related to "Lipid metabolism." Highlighted genes related to FA profile include ECI2, PCYT2, DCXR, G6PC3, PYCR1, and ALG12 in IS, and CYP17A1, ACO2, PI4K2A, GOT1, GPT, NT5C2, PDE6G, POLR3H, and COX15 in IH. Overall, the breed-specific association outcomes reflect differences in the genetic backgrounds of the IS and IH breeds and their selective breeding histories.

Genome-wide association studies for seven production traits highlight genomic regions useful to dissect dry-cured ham quality and production traits in Duroc heavy pigs.

Protected designation of origin dry-cured hams are obtained from heavy pigs (slaughtered at about 160 kg of live weight). A specific breeding program designed to improve meat quality for this production has included as key traits the level of intermuscular fat between the leg muscles and ham weight loss during the seasoning period together with a balance between fat and lean cuts. In this study we carried out genome-wide association studies for seven traits used in the genetic merit of Italian Duroc heavy pigs, five related to meat and carcass quality traits (visible intermuscular fat, ham weight loss at first salting, backfat thickness, ham weight and lean cuts), and two related to performance and efficiency traits (average daily gain and feed : gain ratio). A total of 573 performance-tested pigs were genotyped with the Illumina PorcineSNP60 BeadChip and genome-wide association analyses were carried out using the Bayes B approach with the 1 Mb window option of GenSel and random residuals for each of the seven traits. Detected windows were supported by independent single nucleotide polymorphism analyses with a linear mixed model (LMM) approach on the same animals for the same traits. A total of 30 windows identifying different quantitative trait loci (QTL) were detected and among those, 27 were confirmed by LMM in one of these traits. Among the confirmed windows, three QTL were reported for visible intermuscular fat, seven for ham weight loss at first salting and five and four for backfat thickness and lean cut, respectively. A total of eight QTL were detected for the other production traits. No overlapping QTL were reported except for one window on porcine chromosome 10 between lean cuts and ham weight that contained the CACNB2 gene that has been already associated with loin marbling score in other Duroc pigs. Several regions contained genes that have been already associated with production traits in other pig breeds, including Duroc lines, related to fat deposition or muscle structure. This work reports, for the first time, genome-wide association study results for several traits in Italian Duroc heavy pigs. These results will be useful to dissect the genetic basis for dry-cured ham production traits that determine the total genetic merit index of Italian Duroc pigs.

Transcriptional profiling of swine mammary gland during the transition from colostrogenesis to lactogenesis using RNA sequencing.

BACKGROUND: Colostrum and milk are essential sources of antibodies and nutrients for the neonate, playing a key role in their survival and growth. Slight abnormalities in the timing of colostrogenesis/lactogenesis potentially threaten piglet survival. To further delineate the genes and transcription regulators implicated in the control of the transition from colostrogenesis to lactogenesis, we applied RNA-seq analysis of swine mammary gland tissue from late-gestation to farrowing. Three 2nd parity sows were used for mammary tissue biopsies on days 14, 10, 6 and 2 before (-) parturition and on day 1 after (+) parturition. A total of 15 mRNA libraries were sequenced on a HiSeq2500 (Illumina Inc.). The Dynamic Impact Approach and the Ingenuity Pathway Analysis were used for pathway analysis and gene network analysis, respectively. RESULTS: A large number of differentially expressed genes were detected very close to parturition (-2d) and at farrowing (+ 1d). The results reflect the extraordinary metabolic changes in the swine mammary gland once it enters into the crucial phases of lactogenesis and underscore a strong transcriptional component in the control of colostrogenesis. There was marked upregulation of genes involved in synthesis of colostrum and main milk components (i.e. proteins, fat, lactose and antimicrobial factors) with a pivotal role of CSN1S2, LALBA, WAP, SAA2, and BTN1A1. The sustained activation of transcription regulators such as SREBP1 and XBP1 suggested they help coordinate these adaptations. CONCLUSIONS: Overall, the precise timing for the transition from colostrogenesis to lactogenesis in swine mammary gland remains uncharacterized. However, our transcriptomic data support the hypothesis that the transition occurs before parturition. This is likely attributable to upregulation of a wide array of genes including those involved in 'Protein and Carbohydrate Metabolism', 'Immune System', 'Lipid Metabolism', 'PPAR signaling pathway' and 'Prolactin signaling pathway' along with the activation of transcription regulators controlling lipid synthesis and endoplasmic reticulum biogenesis and stress response.

MAP2 IHC detection: a marker of antigenicity in CNS tissues.

Immunohistochemistry (IHC) is used to detect antibody-specific antigens in tissues; the results depend on the ability of the primary antibodies to bind to their antigens. Therefore, results depend on the quality of preservation of the specimen. Many investigators have overcome the deleterious effects of over-fixation on the binding of primary antibodies to specimen antigens using IHC, but if the specimen is under-fixed or fixation is delayed, false negative results could be obtained despite certified laboratory practices. Microtubule-associated protein 2 (MAP2) is an abundant microtubule-associate protein that participates in the outgrowth of neuronal processes and synaptic plasticity; it is localized primarily in cell bodies and dendrites of neurons. MAP2 immunolabeling has been reported to be absent in areas of the entorhinal cortex and hippocampus of Alzheimer's disease brains that were co-localized with the dense-core type of amyloid plaques. It was hypothesized that the lack of MAP2 immunolabeling in these structures was due to the degradation of the MAP2 antigen by the neuronal proteases that were released as the neurons lysed leading to the formation of these plaques. Because MAP2 is sensitive to proteolysis, we hypothesized that changes in MAP2 immunolabeling may be correlated with the degree of fixation of central nervous system (CNS) tissues. We detected normal MAP2 immunolabeling in fixed rat brain tissues, but MAP2 immunolabeling was decreased or lost in unfixed and delayed-fixed rat brain tissues. By contrast, two ubiquitous CNS-specific markers, myelin basic protein and glial fibrillary acidic protein, were unaffected by the degree of fixation in the same tissues. Our observations suggest that preservation of various CNS-specific antigens differs with the degree of fixation and that the lack of MAP2 immunolabeling in the rat brain may indicate inadequate tissue fixation. We recommend applying MAP2 IHC for all CNS tissues as a pre-screen to assess the quality of the tissue preservation and to avoid potentially false negative IHC results.

Quantitative 177Lu SPECT imaging using advanced correction algorithms in non-reference geometry.

Peptide receptor therapy with 177Lu-labelled somatostatin analogues is a promising tool in the management of patients with inoperable or metastasized neuroendocrine tumours. The aim of this work was to perform accurate activity quantification of 177Lu in complex anthropomorphic geometry using advanced correction algorithms. Acquisitions were performed on the higher 177Lu photopeak (208keV) using a Philips IRIX gamma camera provided with medium-energy collimators. System calibration was performed using a 16mL Jaszczak sphere surrounded by non-radioactive water. Attenuation correction was performed using µ-maps derived from CT data, while scatter and septal penetration corrections were performed using the transmission-dependent convolution-subtraction method. SPECT acquisitions were finally corrected for dead time and partial volume effects. Image analysis was performed using the commercial QSPECT software. The quantitative SPECT approach was validated on an anthropomorphic phantom provided with a home-made insert simulating a hepatic lesion. Quantitative accuracy was studied using three tumour-to-background activity concentration ratios (6:1, 9:1, 14:1). For all acquisitions, the recovered total activity was within 12% of the calibrated activity both in the background region and in the tumour. Using a 6:1 tumour-to-background ratio the recovered total activity was within 2% in the tumour and within 5% in the background. Partial volume effects, if not properly accounted for, can lead to significant activity underestimations in clinical conditions. In conclusion, accurate activity quantification of 177Lu can be obtained if activity measurements are performed with equipment traceable to primary standards, advanced correction algorithms are used and acquisitions are performed at the 208keV photopeak using medium-energy collimators.

Gamma camera calibration and validation for quantitative SPECT imaging with (177)Lu.

Over the last years (177)Lu has received considerable attention from the clinical nuclear medicine community thanks to its wide range of applications in molecular radiotherapy, especially in peptide-receptor radionuclide therapy (PRRT). In addition to short-range beta particles, (177)Lu emits low energy gamma radiation of 113keV and 208keV that allows gamma camera quantitative imaging. Despite quantitative cancer imaging in molecular radiotherapy having been proven to be a key instrument for the assessment of therapeutic response, at present no general clinically accepted quantitative imaging protocol exists and absolute quantification studies are usually based on individual initiatives. The aim of this work was to develop and evaluate an approach to gamma camera calibration for absolute quantification in tomographic imaging with (177)Lu. We assessed the gamma camera calibration factors for a Philips IRIX and Philips AXIS gamma camera system using various reference geometries, both in air and in water. Images were corrected for the major effects that contribute to image degradation, i.e. attenuation, scatter and dead- time. We validated our method in non-reference geometry using an anthropomorphic torso phantom provided with the liver cavity uniformly filled with (177)LuCl3. Our results showed that calibration factors depend on the particular reference condition. In general, acquisitions performed with the IRIX gamma camera provided good results at 208keV, with agreement within 5% for all geometries. The use of a Jaszczak 16mL hollow sphere in water provided calibration factors capable of recovering the activity in anthropomorphic geometry within 1% for the 208keV peak, for both gamma cameras. The point source provided the poorest results, most likely because scatter and attenuation correction are not incorporated in the calibration factor. However, for both gamma cameras all geometries provided calibration factors capable of recovering the activity in anthropomorphic geometry within about 10% (range -11.6% to +7.3%) for acquisitions at the 208keV photopeak. As a general rule, scatter and attenuation play a much larger role at 113keV compared to 208keV and are likely to hinder an accurate absolute quantification. Acquisitions of only the (177)Lu main photopeak (208keV) are therefore recommended in clinical practice. Preliminary results suggest that the gamma camera calibration factor can be assessed with a standard uncertainty below (or of the order of) 3% if activity is determined with equipment traceable to primary standards, accurate volume measurements are made, and an appropriate chemical carrier is used to allow a homogeneous and stable solution to be used during the measurements.

MTHFR-1298 A>C (rs1801131) is a predictor of survival in two cohorts of stage II/III colorectal cancer patients treated with adjuvant fluoropyrimidine chemotherapy with or without oxaliplatin.

Adjuvant treatment based on fluoropyrimidines (FL) improves the prognosis of stage II/III colorectal cancer (CRC). Validated predictive/prognostic biomarkers would spare therapy-related morbidity in patients with a good prognosis. We compared the impact of a set of 22 FL-related polymorphisms with the prognosis of two cohorts of CRC patients treated with adjuvant FL with or without OXA, including a total of 262 cases. 5,10-Methylentetrahydrofolate reductase (MTHFR) MTHFR-1298 A>C (rs1801131) polymorphism had a concordant effect: MTHFR-rs1801131-1298CC genotype carriers had a worse disease free survival (DFS) in both the cohorts. In the pooled population MTHFR-rs1801131-1298CC carriers had also a worse overall survival. We computed a clinical score related to DFS including MTHFR-rs1801131, tumor stage, sex and tumor location, where rs1801131 is the most detrimental factor (hazard ratio=5.3, 95% confidence interval=2.2-12.9; P-value=0.0006). MTHFR-rs1801131 is a prognostic factor that could be used as an additional criteria for the choice of the proper adjuvant regimen in stage II/III colorectal cancer patients.

Technical note: Advantages and limitations of authenticating Palmera goat dairy products by pyrosequencing the melanocortin 1 receptor (MC1R) gene.

Inferring the breed of origin of dairy products can be achieved through molecular analysis of genetic markers with a population-specific pattern of segregation. The goal of the current work was to generate such markers in goats by resequencing several pigmentation genes [melanocortin 1 receptor (MC1R), v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT), tyrosinase (TYR), and tyrosinase-related protein 2 (TYRP2)]. This experiment revealed 10 single nucleotide polymorphisms (SNP), including 5 missense mutations and 1 nonsense mutation. These markers were genotyped in 560 goats from 18 breeds originally from Italy, the Iberian Peninsula, the Canary Islands, and North Africa. Although the majority of SNP segregated at moderate frequencies in all populations (including 2 additional markers that were used as a source of information), we identified a c.764G>A SNP in MC1R that displayed highly divergent allelic frequencies in the Palmera breed compared with the Majorera and Tinerfeña breeds from the Canary Islands. Thus, we optimized a pyrosequencing-based technique that allowed us to estimate, very accurately, the allele frequencies of this marker in complex DNA mixtures from different individuals. Once validated, we applied this method to generating breed-specific DNA profiles that made it possible to detect fraudulent cheeses in which Palmero cheese was manufactured with milk from Majorera goats. One limitation of this approach, however, is that it cannot be used to detect illegal manufacturing where Palmero dairy products are produced by mixing milk from Palmera and Majorera goats, because the c.764G>A SNP segregates in both breeds.

Genome-wide analysis of Italian sheep diversity reveals a strong geographic pattern and cryptic relationships between breeds.

Italy counts several sheep breeds, arisen over centuries as a consequence of ancient and recent genetic and demographic events. To finely reconstruct genetic structure and relationships between Italian sheep, 496 subjects from 19 breeds were typed at 50K single nucleotide polymorphism loci. A subset of foreign breeds from the Sheep HapMap dataset was also included in the analyses. Genetic distances (as visualized either in a network or in a multidimensional scaling analysis of identical by state distances) closely reflected geographic proximity between breeds, with a clear north-south gradient, likely because of high levels of past gene flow and admixture all along the peninsula. Sardinian breeds diverged more from other breeds, a probable consequence of the combined effect of ancient sporadic introgression of feral mouflon and long-lasting genetic isolation from continental sheep populations. The study allowed the detection of previously undocumented episodes of recent introgression (Delle Langhe into the endangered Altamurana breed) as well as signatures of known, or claimed, historical introgression (Merino into Sopravissana and Gentile di Puglia; Bergamasca into Fabrianese, Appenninica and, to a lesser extent, Leccese). Arguments that would question, from a genomic point of view, the current breed classification of Bergamasca and Biellese into two separate breeds are presented. Finally, a role for traditional transhumance practices in shaping the genetic makeup of Alpine sheep breeds is proposed. The study represents the first exhaustive analysis of Italian sheep diversity in an European context, and it bridges the gap in the previous HapMap panel between Western Mediterranean and Swiss breeds.

Tissue-specific downregulation of the adiponectin "system": possible implications for fat accumulation tendency in the pig.

Adiponectin's beneficial effects are mediated by the AdipoR1 and AdipoR2 receptors (AdipoRs). The pig is a good model to study complex disorders such as obesity. We analyzed the expression of adiponectin, AdipoRs and some key molecules of energy metabolism (AMP-activated protein kinase α [AMPKα], p38 mitogen-activated protein kinase [p38 MAPK], and PPARα) in 2 pig breeds that displayed an opposite genetic behavior for energy metabolism: Casertana (CE), a fat-type animal, and Large White (LW), a lean-type animal. Muscle, liver, visceral and subcutaneous adipose tissues, and brain tissues were examined. The AdipoRs cDNA sequences were identical in the 2 breeds. AdipoRs mRNA expression, measured in all tissues, was significantly lower only in the 2 adipose tissues of CE pigs (P < 0.05). The muscle expression of AdipoRs, AMPKα, p38 MAPK, and PPARα was lower in CE than in LW animals (P < 0.01, P < 0.05, P < 0.01, P < 0.01, respectively). In liver, no molecule differed between breeds. The expression of both AdipoRs in visceral and subcutaneous adipose tissues was lower in CE pigs (P < 0.01). In brain, AdipoR1 and AMPKα expression was lower in CE pigs (P < 0.01), whereas AdipoR2 tended to be lower in CE than LW pigs (P = 0.05). In conclusion, our results suggest that tissue-specific downregulation of Adiponectin, AdipoRs, and of the key molecules of energy metabolism may be associated with the tendency of CE pigs to accumulate fat.