FOXOs transcription factors not only play key roles in glucose metabolism, muscle atrophy and energy homeostasis but also play crucial transcriptional regulatory roles in the cell's metabolism, orchestrating programs of gene expression that regulate cell apoptosis, cell-cycle progression and oxidative stress resistance. However, the specific function of FOXOs promoting fibroblasts proliferation and apoptosis are still unknown. Thus, we used the High-Resolution Melting (HRM) and RNA interference methods to detect SNPs and function. We found one SNP in the exon of FOXO1, three SNPs were identified in the exon of FOXO3, and three SNPs and production traits were significantly different. The siRNA sequence of yak FOXO1 and FOXO3 were transfected into the yak fibroblasts, and effects were detected by a series of assays to reveal the function in yak fibroblasts. The results demonstrated that down-regulated expression of FOXO1 and FOXO3 resulted in up-regulated the expression of BAX, Caspase9 and Caspase3, and down-regulated the expression level of anti-apoptotic gene of BCL2. The apoptotic situation was consistent with results of the flow cytometry and Tunel test cell cycle and cell vitality results revealed that knockdown FOXO1 and FOXO3 resulted in increased P27 expression level and decreased CyclinD1. Meanwhile, cell vitality was also decreased. These results demonstrated that FOXO1 and FOXO3 are two novel regulatory factors to suppress cells proliferation and promote cells apoptosis. Furthermore, these results provide evidence that FOXO1 and FOXO3 play a functional role in cell apoptosis.
We first conducted time-series analysis of mono- and dinucleotide composition for over 10,000 SARS-CoV-2 genomes, as well as over 1500 Zaire ebolavirus genomes, and found clear time-series changes in the compositions on a monthly basis, which should reflect viral adaptations for efficient growth in human cells. We next developed a sequence alignment free method that extensively searches for advantageous mutations and rank them in an increase level for their intrapopulation frequency. Time-series analysis of occurrences of oligonucleotides of diverse lengths for SARS-CoV-2 genomes revealed seven distinctive mutations that rapidly expanded their intrapopulation frequency and are thought to be candidates of advantageous mutations for the efficient growth in human cells.
BACKGROUND:The accurate identification of the exon/intron boundaries is critical for the correct annotation of genes with multiple exons. Donor and acceptor splice sites (SS) demarcate these boundaries. Therefore, deriving accurate computational models to predict the SS are useful for functional annotation of genes and genomes, and for finding alternative SS associated with different diseases. Although various models have been proposed for the in silico prediction of SS, improving their accuracy is required for reliable annotation. Moreover, models are often derived and tested using the same genome, providing no evidence of broad application, i.e. to other poorly studied genomes.RESULTS:With this in mind, we developed the Splice2Deep models for SS detection. Each model is an ensemble of deep convolutional neural networks. We evaluated the performance of the models based on the ability to detect SS in Homo sapiens, Oryza sativa japonica, Arabidopsis thaliana, Drosophila melanogaster, and Caenorhabditis elegans. Results demonstrate that the models efficiently detect SS in other organisms not considered during the training of the models. Compared to the state-of-the-art tools, Splice2Deep models achieved significantly reduced average error rates of 41.97% and 28.51% for acceptor and donor SS, respectively. Moreover, the Splice2Deep cross-organism validation demonstrates that models correctly identify conserved genomic elements enabling annotation of SS in new genomes by choosing the taxonomically closest model.CONCLUSIONS:The results of our study demonstrated that Splice2Deep both achieved a considerably reduced error rate compared to other state-of-the-art models and the ability to accurately recognize SS in other organisms for which the model was not trained, enabling annotation of poorly studied or newly sequenced genomes. Splice2Deep models are implemented in Python using Keras API; the models and the data are available at https://github.com/SomayahAlbaradei/Splice_Deep.git.
Mouse Ptchd3 (patched domain containing 3) was previously identified as a male germ-cell specific gene. The protein product of this gene has been found on the surface of mouse, rat and human sperm. Since Ptchd3 contains a conserved patched domain, we hypothesize that it functions as a membrane receptor for the hedgehog ligand. Herein, we used a Ptchd3 knockout mouse model to study its function in mouse development and spermatogenesis. We found that Ptchd3 knockout mice were born and lived normally. The fertility and sperm production of knockout males were not changed. Moreover, our data indicated that the expression levels of several hedgehog signaling genes were not affected in mutant testis. Taken together, these findings demonstrate that Ptchd3 is a non-essential gene in mouse development and spermatogenesis.
BACKGROUND:Human mesenchymal stromal cells (MSCs) phenotypically share their positive expression of the International Society for Cell and Gene Therapy (ISCT) markers CD73, CD90 and CD105 with fibroblasts. Fibroblasts are often co-isolated as an unwanted by-product from biopsy and they can rapidly overgrow the MSCs in culture. Indeed, many other surface markers have been proposed, though no unique MSC specific marker has been identified yet. Quantitative PCR (qPCR) is a precise, efficient and rapid method for gene expression analysis. To identify a marker suitable for accurate MSC characterisation, qPCR was exploited.METHODS AND RESULTS:Two commercially obtained bone marrow (BM) derived MSCs and an hTERT immortalised BM-MSC line (MSC-TERT) have been cultured for different days and at different oxygen levels before RNA extraction. Together with RNA samples previous extracted from umbilical cord derived MSCs and MSC-TERT cells cultured in 2D or 3D, this heterogeneous sample set was quantitatively analysed for the expression levels of 18 candidate MSC marker genes. The expression levels in MSCs were compared with the expression levels in fibroblasts to verify the differentiation capability of these genes between MSCs and fibroblasts. None of the ISCT markers could differentiate between fibroblasts and MSCs. A total of six other genes (ALCAM, CLIC1, EDIL3, EPHA2, NECTIN2, and TMEM47) were identified as possible biomarkers for accurate identification of MSCs.CONCLUSION:Justified by considerations on expression level, reliability and specificity, Activated-Leukocyte Cell Adhesion Molecule (ALCAM) was the best candidate for improving the biomarker set of MSC identification.
Post-fermentation fungal biomass waste provides a viable source for chitin. Cell wall chitin of filamentous fungi, and in particular its de-N-acetylated derivative chitosan, has a wide range of commercial applications. Although the cell wall of filamentous fungi comprises 10-30% chitin, these yields are too low for cost-effective production. Therefore, we aimed to identify the genes involved in increased chitin deposition by screening a collection of UV-derived cell wall mutants in Aspergillus niger. This screen revealed a mutant strain (RD15.4#55) that showed a 30-40% increase in cell wall chitin compared to the wild type. In addition to the cell wall chitin phenotype, this strain also exhibited sensitivity to SDS and produces an unknown yellow pigment. Genome sequencing combined with classical genetic linkage analysis identified two mutated genes on chromosome VII that were linked with the mutant phenotype. Single gene knockouts and subsequent complementation analysis revealed that an 8 bp deletion in NRRL3_09595 is solely responsible for the associated phenotypes of RD15.4#55. The mutated gene, which was named cwcA (cell wall chitin A), encodes an orthologue of Saccharomyces cerevisiae Bypass of ESS1 (BYE1), a negative regulator of transcription elongation. We propose that this conserved fungal protein is involved in preventing cell wall integrity signaling under non-inducing conditions, where loss of function results in constitutive activation of the cell wall stress response pathway, and consequently leads to increased chitin content in the mutant cell wall.
A previous autosomal STR study provided evidence of a connection between the ancient Soliga tribe at the southern tip of the Indian subcontinent and Australian aboriginal populations, possibly reflecting an eastbound coastal migration circa (15 Kya). The Soliga are considered to be among India's earliest inhabitants. In this investigation, we focus on the Y chromosomal characteristics shared between the Soliga population and other Indian tribes as well as western Eurasia and Sub-Saharan Africa groups. Some noteworthy findings of this present analysis include the following: The three most frequent haplogroups detected in the Soliga population are F*, H1 and J2. F*, the oldest (43 to 63 Kya), has a significant frequency bias in favor of Indian tribes versus castes. This observation coupled with the fact that Y-STR haplotypes shared with sub-Saharan African populations are found only in F* males of the Soliga, Irula and Kurumba may indicate a unique genetic connection between these Indian tribes and sub-Saharan Africans. In addition, our study suggests that haplogroup H is confined mostly to South Asia and immediate neighbors and the H1 network may indicate minimal sharing of Y-STR haplotypes among South Asian collections, tribal and otherwise. Also, J2, brought into India by Neolithic farmers, is present at a significantly higher frequency in caste versus tribal communities. This last observation may reflect the marginalization of Indian tribes to isolated regions not ideal for agriculture.
Mechanical loading-related strains trigger bone formation by osteoblasts while suppressing resorption by osteoclasts, uncoupling the processes of formation and resorption. Osteocytes may orchestrate this process in part by secreting sclerostin (SOST), which inhibits osteoblasts, and expressing receptor activator of nuclear factor-κB ligand (RANKL/TNFSF11) which recruits osteoclasts. Both SOST and RANKL are targets of the master osteoblastic transcription factor RUNX2. Subjecting human osteoblastic Saos-2 cells to strain by four point bending down-regulates their expression of SOST and RANKL without altering RUNX2 expression. RUNX2 knockdown increases basal SOST expression, but does not alter SOST down-regulation following strain. Conversely, RUNX2 knockdown does not alter basal RANKL expression, but prevents its down-regulation by strain. Chromatin immunoprecipitation revealed RUNX2 occupies a region of the RANKL promoter containing a consensus RUNX2 binding site and its occupancy of this site decreases following strain. The expression of epigenetic acetyl and methyl writers and readers was quantified by RT-qPCR to investigate potential epigenetic bases for this change. Strain and RUNX2 knockdown both down-regulate expression of the bromodomain acetyl reader BRD2. BRD2 and RUNX2 co-immunoprecipitate, suggesting interaction within regulatory complexes, and BRD2 was confirmed to interact with the RUNX2 promoter. BRD2 also occupies the RANKL promoter and its occupancy was reduced following exposure to strain. Thus, RUNX2 may contribute to bone remodeling by suppressing basal SOST expression, while facilitating the acute strain-induced down-regulation of RANKL through a mechanosensitive epigenetic loop involving BRD2.
Dehydrins (DHNs) play critical roles in plant adaptation to abiotic stresses. The objective of this study was to characterize DHNs in bermudagrass (Cynodon spp.). CdDHN4 gene was cloned from bermudagrass 'Tifway'. Two CdDHN4 transcripts were detected due to alternative splicing (the nonspliced CdDHN4-L and the spliced CdDHN4-S) and both the CdDHN4-S and CdDHN4-L proteins are YSK2-type DHNs, the Φ-segment is present in CdDHN4-L and absent in CdDHN4-S. Transgenic Arabidopsis thaliana expressing CdDHN4-L or CdDHN4-S exhibited improved tolerance to salt, osmotic, low temperature and drought stress compared to the wild type (WT). The two transgenic lines did not differ in salt or drought tolerance, while plants expressing CdDHN4-S grew better under osmotic stress than those expressing CdDHN4-L. Both transgenic lines exhibited reduced content of malondialdehyde (MDA) and reactive oxygen species (ROS); and higher antioxidant enzymatic activities than the wild type plants under salt or drought stress. CdDHN4-S exhibited a higher ROS-scavenging capacity than CdDHN4-L.
CircRNA (circular RNA) is a kind of closed circular structure of noncoding RNA molecules without 5' hat structure and 3' polyA, mainly located in the cytoplasm or stored in exosomes. It is not affected by RNA exonuclease, so it's stable and hard to be degraded. Proved to be widespread in a variety of eukaryotes, most circRNAs are cyclized by exons, some are lasso structures formed by intron cyclization. Recently, circRNAs have been demonstrated to play crucial roles in cardiomyocyte hypertrophy, fibrosis, autophagy and apoptosis, participating in the development of heart failure. There is increasing evidence that circRNAs may be a novel target for the treatment of heart failure.
Despite the progress made in AAV-based gene therapy targeting different organ systems, lung-targeted gene therapy using AAV vectors has not been effective, mostly due to the poor transduction and un-sustained gene expression in airway epithelium. Furthermore, concerns over possible harmful insertional mutagenesis seen in other cell types, particularly hepatocytes, raised a question about AAV safety. In this study, we evaluate the long-term persistence of this vector in mouse lungs and any possible harmful integration of these vectors into the host genome. AAV6 vectors expressing reporter gene (firefly luciferase) were delivered to the lungs of C57BL/6 mice through intra-tracheal intubation. Despite the large variation among individual animals, most animals had high and sustained luciferase activity with a peak from 2 to 3 weeks post-transduction before a significant decline between 15 and 19 weeks post-transduction. More importantly, even after its decline, most animals maintained detectable luciferase expression for 150 days or more, which was confirmed by post-necropsy qPCR analysis of luciferase gene expression. At the termination point of experiments, an average of one copy of AAV expression cassette per mouse genome was detected. We also found that partial overlaps between the AAV6 expression cassette and the mouse genome were distributed broadly with no apparent systematic preference in any mouse chromosomal map location. In summary, our data suggest that AAV6 mediated long-term gene expression in the lungs with no evidence of genomic integration, and thus, any insertional mutagenesis.
Black/African-American (B/AA) breast cancer patients tend to have more aggressive tumor biology compared to White/Caucasians. In this study, a variety of breast tumor molecular expression profiles of patients derived from the two racial groupings were investigated. Breast invasive carcinoma sample data (RNASeq version 2, Reverse Phase Protein Array, mutation, and miRSeq data) from the Cancer Genome Atlas were examined. The results affirm that B/AA patients are more likely than Caucasian patients to harbor the aggressive basal-like or the poor prognosis-associated HER2-enriched molecular subtypes of breast cancer. There is also a higher incidence of the triple-negative breast cancer (TNBC) among B/AA patients than the general population, a fact reflected in the mutation patterns of genes such as PIK3CA and TP53. Furthermore, an immortalization signature gene set, is enriched in samples from B/AA patients. Among stage III patients, TERT, DRAP1, and PQBP1, all members of the immortalization gene signature set, are among master-regulators with increased activity in B/AA patients. Master-regulators driving differences in expression profiles between the two groups include immortalization markers, senescence markers, and immune response and redox gene products. Differences in expression, between B/AA and Caucasian patients, of RB1, hsa-let-7a, E2F1, c-MYC, TERT, and other biomolecules appear to cooperate to enhance entry into the S-phase of the cell cycle in B/AA patients. Higher expression of miR-221, an oncomiR that facilitates entry into the cell cycle S-phase, is regulated by c-MYC, which is expressed more in breast cancer samples from B/AA patients. Furthermore, the cell migration- and invasion-promoting miRNA, miR-135b, has increased relative expression in B/AA patients. Knock down of the immortalization marker TERT inhibited triple-negative breast cancer cell lines (MDA-MB-231 and MDA-MB-468) cell viability and decreased expression of TERT, MYC and WNT11. For those patients with available survival data, prognosis of stage II patients 50 years of age or younger at diagnosis, was distinctly poorer in B/AA patients. Also associated with this subset of B/AA patients are missense mutations in HUWE1 and PTEN expression loss. Relative to Caucasian non-responders to endocrine therapy, B/AA non-responders show suppressed expression of a signature gene set on which biological processes including signaling by interleukins, circadian clock, regulation of lipid metabolism by PPARα, FOXO-mediated transcription, and regulation of TP53 degradation are over-represented. Thus, we identify molecular expression patterns suggesting diminished response to oxidative stress, changes in regulation of tumor suppressors/facilitators, and enhanced immortalization in B/AA patients are likely important in defining the more aggressive molecular tumor phenotype reported in B/AA patients.
Hyperglycemia activates innate leukocytes such as monocytes and induces pro-inflammatory cytokine expression, resulting in increased monocyte adhesion to aortic endothelial cells. In this study, we investigated whether high glucose and/or tumor necrosis factor (TNF) would enhance pro-inflammatory cytokine expression of tumor necrosis factor (TNF) and interleukin (IL)-1β (IL1B) by altering histone modifications in U937, a juvenile macrophage cell line. The mRNA levels of TNF and IL1B in U937 cells were significantly affected by glucose concentration and TNF treatment. Mono-methylated histone H3K4 signals around TNF and IL1B were lower in cells treated with high glucose compared with low glucose. Conversely, tri-methylated histone H3K4 and H3K36 signals were higher in cells treated with high glucose compared with low glucose. TNF treatment of U937 cells cultured in high glucose enhanced histone H3K36 tri-methylation, particularly around the gene regions of TNF and IL1B. Histone acetylation was induced by treatment with TNF in high-glucose medium. The induction of acetylation and tri-methylation of K4 and K36 of histone H3 around TNF and IL1B by treatment with high glucose and/or TNF was positively associated with the induction of these genes in juvenile macrophage U937 cells.
Breast cancer is the most common female malignancy and the major cause of cancer-related death in women. Long non-coding RNAs (lncRNAs), as oncogenic or tumor suppressor factor, involved in the development and progression of various cancers. In this study, we sought to investigate the function of lncRNA CBR3-AS1 in breast cancer. We evaluated the expression pattern of CBR3-AS1 in breast cancer tissues and cell lines, explored the correlation between CBR3-AS1 expression and the survival time of breast cancer patients, and probed the effect of CBR3-AS1 on tumor progression of breast cancer through loss-of-function and gain-of-function strategies. Our results showed that CBR3-AS1 was overexpressed in breast cancer tissues and cell lines and predicted the prognosis of breast cancer patients. And CBR3-AS1 exerted biological function as an oncogenic lncRNA, involved in the regulation of cell proliferation, colony formation, apoptosis and tumor growth in breast cancer. Taken together, CBR3-AS1 was up-regulated in breast cancer and promoted the risk of breast cancer. It may be a novel therapeutic target and potential prognostic marker for breast cancer.
Lem2 family proteins, i.e. the LAP2-Emerin-MAN1 (LEM) domain-containing nuclear envelope proteins, are well-conserved from yeasts to humans, both of which belong to the Opisthokonta supergroup. However, whether their homologs are present in other eukaryotic phylogenies remains unclear. In this study, we identified two Lem2 homolog proteins, which we named as Lem2 and MicLem2, in a ciliate Tetrahymena thermophila belonging to the SAR supergroup. Lem2 was localized to the nuclear envelope of the macronucleus (MAC) and micronucleus (MIC), while MicLem2 was exclusively localized to the nuclear envelope of the MIC. Immunoelectron microscopy revealed that Lem2 in T. thermophila was localized to both the inner and outer nuclear envelopes of the MAC and MIC, while MicLem2 was mostly localized to the nuclear pores of the MIC. Molecular domain analysis using GFP-fused protein showed that the N-terminal and luminal domains, including the transmembrane segments, are responsible for nuclear envelope localization. During sexual reproduction, enrichment of Lem2 occurred in the nuclear envelopes of the MAC and MIC to be degraded, while MicLem2 was enriched in the nuclear envelope of the MIC that escaped degradation. These findings suggest the unique characteristics of Tetrahymena Lem2 proteins. Our findings provide insight into the evolutionary divergence of nuclear envelope proteins.
Reverse-Transcription quantitative PCR (RT-qPCR) provides a valuable tool to study gene expression with exquisite sensitivity. To retain its inferential power, user-introduced technical variability must be reduced and accounted for. Selecting a set of stably expressed internal control genes (ICG), validated for each experimental condition/sample set, is widely accepted as a reliable way to normalize RT-qPCR data and account for said variability. Despite significant efforts in establishing standardized and resource-efficient normalization approaches, numerous recent reports have underlined deficiencies in the state of RT-qPCR normalization. Livestock science has benefitted tremendously from the use of RT-qPCR; however, the issue of lack of proper normalization likely affects this discipline as well. We thus decided to determine whether this is true, and to which extent. We conducted an in-depth analysis of all (225) RT-qPCR articles published in the six most prominent livestock journals in the field from 2013 to 2017. A quantitative scale was constructed, and values were assigned to each article based on the number of ICG used, the use of a publicly available algorithm to assess the reliability of ICG, and the reporting of pertinent information related to ICG (ranges from 0 = total noncompliance - to 100 = total compliance). Out of the surveyed group, only 10.7% of the publications obtained a score of 100, while the largest group (n = 158) was represented by articles that scored 0. Subdividing articles based on whether an algorithm to validate ICG was used (YAL) or not (NAL) revealed the use of a larger number of ICG to normalize RT-qPCR in the YAL group compared to NAL (1.4-fold more, 95% C.I.: 1.11-1.84) and was closer to the "gold standard" of three ICG. Using an algorithm also increased the diversity of ICG and significantly reduced the use of RNA18S, whose suitability as ICG has been thoroughly debated. These remarkably low normalization standards are likely to generate questionable results that can severely hinder the advance of transcriptomic studies in livestock science and related fields.
The paired-type homeodomain transcription factor Uncx is involved in multiple processes of embryogenesis in vertebrates. Reasoning that zebrafish genes uncx4.1 and uncx are orthologs of mouse Uncx, we studied their genomic environment and developmental expression. Evolutionary analyses indicate the zebrafish uncx genes as being paralogs deriving from teleost-specific whole-genome duplication. Whole-mount in situ mRNA hybridization of uncx transcripts in zebrafish embryos reveals novel expression domains, confirms those previously known, and suggests sub-functionalization of paralogs. Using genetic mutants and pharmacological inhibitors, we investigate the role of signaling pathways on the expression of zebrafish uncx genes in developing somites. In identifying putative functional role(s) of zebrafish uncx genes, we hypothesized that they encode transcription factors that coordinate growth and innervation of somitic muscles.
Vitiligo is the most common skin pigmentation disorder which affects around 1% of the population worldwide. The disease has complex pathogenesis and is of multifactorial etiology, that finally culminates in patchy depigmentation of skin. Genetic contribution to the disease is well studied, however the information about multiple associated genes and contributing variations are scattered across the literature. To address this complex disorder affecting the skin, we systematically cataloged the genes and variations by creating a Locus Specific Database for vitiligo called, “VitiVar”. This comprehensive resource houses manually curated 322 genes and 254 variations, from 202 articles indexed in PubMed. We applied an integrative approach to stratify genes and variations to facilitate dissection of vitiligo pathogenesis by layering it with expression status in specific constituent cell types of skin and in-house vitiligo expression data. Finally, we were able to demonstrate the utility of VitiVar by generating a vitiligo interactome using GeneMANIA and overlaying the vitiligo and cell type specific information. This interaction network yielded 20 new genes (apart from 322 VitiVar genes) of which we were able to prioritize IFI27 and IFI6 for further validation. This, thereby makes VitiVar a comprehensive integrative platform in unravelling disease biology by providing meaningful leads for functional interrogation. VitiVar is freely accessible to the research community for prioritizing and validating the candidate genes and variations (http://vitivar.igib.res.in/).
Epithelial-mesenchymal transition (EMT) symbolizes the predominant program of advanced-stage cancer, it is critical in cancer progression, metastasis, and chemotherapy resistance. In this study, the metastatic properties of nasopharyngeal carcinoma (NPC) cells were evaluated by morphological examination, wound healing assay, migration and invasion assay. Western blotting and qRT-PCR were used to ascertain the expression of markers which were associated with EMT. The effects of miR-205-5p on invasion, migration, EMT and proliferation of NPC cells were evaluated and the molecular mechanisms of their interaction were explored. In this study, we manifested firstly that the expression of miR-205-5p in cisplatin-resistant NPC cell line HNE1/DDP was obviously up-regulated than that in its parental cell line HNE1. Then we analyzed the specific role of miR-205-5p through functional assays by transfecting specific mimics and inhibitors. The results indicated that low expression of miR-205-5p restrained EMT progression of HNE1/DDP cells. Further studies on the mechanism of miR-205-5p manifested that PTEN was a downstream candidate gene of miR-205-5p, down-regulated PTEN expression could counteract the effect of miR-205-5p inhibitors, and the regulation of EMT by miR-205-5p on HNE1/DDP cells depended on the PI3K/AKT signaling pathway. Overall, our results indicated that miR-205-5p was targeting PTEN to regulate EMT through the PI3K/AKT pathway. This study will supply a new treatment target for advanced NPC.
BACKGROUND:Energy restriction induces adaptations in resting energy expenditure (REE) and physical activity; inter-individual variability could be ascribed to genetic predisposition. The aim was to examine if changes in REE and physical activity as a result of weight loss were affected by candidate single nucleotide polymorphisms (SNPs).METHODS:148 subjects (39 men, 109 women), mean ± SD age: 41 ± 9 year; body mass index (BMI): 31.9 ± 3.0 kg/m2, followed a very low energy diet for 8 weeks. SNPs were selected from six candidate genes: ADRB2, FTO, MC4R, PPARG2, PPARD and PPARGC1A. REE (ventilated hood) and physical activity (tri-axial accelerometer) were assessed before and after the diet. General linear modelling included gender, age and additional relevant covariates for all parameters.RESULTS:The heterozygotic genotype of FTO was associated with a higher amount of physical activity (1.71 Mcounts/d; CI 1.62-1.81) compared to the homozygotic major genotype (1.50 Mcounts/d; CI 1.40-1.59) (P < 0.001) while the homozygotic risk allele genotype was not different (1.56 Mcounts/d; CI 1.39-1.74) at baseline; moreover, a similar pattern was observed after energy restriction. Carrying the homozygotic minor genotype of ADRB2 was associated with a larger decrease in REE (P < 0.05) and greater adaptive thermogenesis (P < 0.05) after weight loss.CONCLUSION:Carrying the minor ADRB2 allele homozygous was associated with a larger diet induced metabolic adaptation in energy expenditure and suggest a central role for reduced lipid mobilization. Carrying the risk allele of FTO homozygous was not associated with lower physical activity at baseline or after weight loss. Heterozygous carriers of one FTO risk allele showed greater physical activity before and after weight loss which might protect them in part from the higher obesity risk associated with FTO.
