Nocturnal red light application affects defence-related enzymes in wheat, in particular antioxidants and glutathione transferases (GSTs), which are crucial for successful plant defence. In our study, we sought to answer the question of whether night-time illumination during anthesis induces detectable changes in the infection responses of wheat cultivars with different levels of Fusarium resistance. To address this question, we investigated a range of factors from yield parameters and membrane status to changes in enzyme activities and gene expression and its regulation. Nocturnal red light treatment increased the activities of superoxide dismutase, catalase, guaiacol-dependent peroxidase and GSTs. In parallel with increased activity of detoxification enzymes, a higher grain yield was observed in the more resistant wheat line during infection by Fusarium graminearum. Notably, GSTs, which are typically down-regulated in darkness, were strongly up-regulated by red light at night in the more susceptible cultivar, especially TaGSTU1B and TaGSTF5. In addition, an exceptionally high and light-dependent transcriptional activity of TaGSTF5 was detected in the sensitive line. Sequence analysis of the regulatory region of TaGSTF5 identified an additional GATA box, a circadian regulatory element, which may be responsible for the increased transcript levels. These results suggest that nocturnal red light can effectively enhance antioxidant and GST activity as part of the defence of wheat against Fusarium head blight, but this depends on the Fusarium resistance of the selected wheat genotypes.

Fusarium head blight is one of the greatest threats to global wheat production. Despite the special attention paid by researchers to resistance genetics, the stability of resistance and the expression of its epidemiological relationships have not been tested in depth. As most studies only present data on visual symptoms, in this study, we present data from four experiments. Here, 15-40 genotypes were tested with four and eight isolates (inocula) in 3-4-year experiments, with 32, 24, 36, and 12 epidemic situations used to determine the disease index (DI), Fusarium-damaged kernels (FDKs), and DON. All genotypes were tested for stability by the variance across epidemics, and the b value of the linear function was considered. Both indices were suitable for measuring stability/instability, but the variance results were more closely correlated with the experimental data than the b value, known as the stability index (SI). The use of variance is recommended due to its simplicity and reliability. In the first test, the rate of maximum/minimum variance for DI, FDK, and DON differed 15-, 20-, and 120-fold, respectively. In the second test, the same rates were 200, 400, and over 4000, with the other tests exhibiting similar tendencies. The traits differ, the epidemics vary, and a dependence on resistance level can be proven. The genotype ranking varies strongly in different epidemics, with approximately 50% of the correlations between variety responses being insignificant. Therefore, many epidemics are needed to obtain a reliable picture of the adaptation ability of the resistance traits and their stability. Approximately 25% of the genotypes tested belong to the most stable group. About 35% were discarded, and in the 40% medium, we observed both highly unstable and moderately stable genotypes. Principal component analysis (PCA) of the three traits in the experiments showed a confirmatory, nearly uniform distribution of genotypes, with a different footprint or "identity card" present for each genotype. The genotypes for the traits belong to one or two groups, although sometimes individual genotypes seem to be independent. No strict rule was found. This underlines the necessity of considering the plant's traits (Di, FDK, and DON) in resistance testing. Highly resistant winter wheat lines could also be bred with very low variance and SI values and very high stability (SI values lower than 0.3). Of the traits, DON is the most important. With this methodology, variety registration also becomes possible. The epidemiological aspect has a decisive role in resistance studies, and without identifying stability in FHB resistance, no food safety estimates can be made.

While the potential of adipocyte thermogenesis in influencing metabolic diseases is well-recognized, its precise regulatory mechanisms remain elusive. To address this, we explore the complex network of transcription factors (TFs) governing the human UCP1 gene, a central player in thermogenesis, to shed light on regulatory processes driving human fat cell phenotypes. By employing computational analyses, we screen UCP1 ortholog and paralog promoters across humans, mice and rats to uncover conserved and species-specific regulatory elements. Leveraging transcriptomic data, chipSeq results and AdioNET phenotyping we delineate TFs potentially bind to the human UCP1 promoter. Significant sequence variation is revealed in the enhancer regions of UCP1s, characterised by the absence of large segments in the rodent genome, potentially influenced by the presence/absence of repetitive elements. Furthermore, our analyses identify species-specific regulatory hotspots mostly recognized by homeodomain family TFs providing the potential for the formation of enhanceosomes with nearby TFs. Exploring phylogenetically conserved regulatory elements reveals TFs exhibiting binding sites across species and UCP paralogs assigning again homeodomain family TFs among others, and bHLH TFs, respectively. These results potentially advance our understanding of thermogenic fat cell development and offer new targets for intervention in metabolic disorders.### Competing Interest StatementThe authors have declared no competing interest.

The endogenous stress metabolite β-aminobutyric acid (BABA) primes plants for enhanced resistance against abiotic and biotic stress by activating a complex phytohormone signaling network that includes abscisic acid (ABA), jasmonic acid (JA), salicylic acid (SA), and ethylene (ET). In this study, through stringent filtering, we identify 14 master regulatory transcription factors (TFs) from the DOF, AHL, and ERF families that potentially regulate the biosynthesis and signaling of these phytohormones. Transcriptional analysis of BABA-treated Arabidopsis thaliana and Hordeum vulgare suggests that DOF family TFs play a crucial role in stress response regulation in both species. BABA treatment in A. thaliana upregulates the TFs MNB1A and PBF and enhances the expression of the genes ICS1, EDS5, and WIN3 in the SA biosynthesis pathway, potentially boosting NPR1 and PR1 in the SA signaling pathway. Conversely, in H. vulgare, the BABA-induced upregulation of TF DOF5.8 may negatively regulate SA biosynthesis by downregulating ICS1, EDS5, and PR1. Additionally, in A. thaliana, BABA triggers the expression of TF PBF, which may result in the decreased expression of MYC2, a key gene in JA signaling. In contrast, H. vulgare exhibits increased expression of ERF2 TF, which could positively regulate the JA biosynthesis genes LOX and Tify9, along with the COI1 and JAZ genes involved in the JA signaling pathway. These findings offer new perspectives on the transcriptional regulation of phytohormones during plant priming.

Toxigenic fungi are among the most significant disease-causing agents in wheat. DON is the most common Fusarium mycotoxin, and for a long time, it was the only toxin researched. However, multitoxin data from wheat samples have drawn attention to the fact that much more toxins can be involved in the wheat toxin story than we supposed earlier. For resistance breeding, we need a more detailed approach to identify toxins that occur above the limit and identify the source of the fungal species that produces them. This study analyzed local wheat varieties for fungal infections and natural multitoxin contamination. Eighteen winter wheat genotypes were tested for fungal contaminations across three different locations in 2021 and 2022. Fourteen different mycotoxins—deoxynivalenol, aflatoxins (B1, B2, G1, and G2), fumonisins (B1 and B2), sterigmatocystin, ochratoxin A, zearalenone, T-2, HT-2, and diacetoxyscirpenol—were analyzed using HPLC/triple-quad MS. Toxigenic species such as Fusarium, Aspergillus, and Penicillium had low rates of occurrence, but the toxin contamination was often surprisingly high. Many samples without corresponding fungal infections were also identified as containing mycotoxins. Therefore, the identified fungal infection is less useful for forecasting toxin level. In conclusion, mycotoxin contamination is decisive. Most samples were contaminated by one or more mycotoxins. Although the mycotoxin concentrations typically remained below EU limits, some samples exhibited higher levels, particularly aflatoxins and Ht-2 toxin. Significant variations were observed across year, location, and genotype. For several toxins, significant genotype differences were identified, supporting the hypothesis that resistance may be a useful and suitable control measure. Stability of toxin contamination across years and locations is a very valuable trait; genotypes were identified with low toxin levels and stability (low variance) to all mycotoxins tested. It seems that, in addition to DON, more attention should be given to aflatoxin B1, B2, and G1, which provided similar concentrations. The HT-2 toxin was present in many samples surpassing EU limits. This is the first report on the dangerous occurrence of preharvest-origin aflatoxins and the HT-2 toxin of wheat in Hungary.

All major ear rots (F. graminearum, F. verticillioides, and Aspergillus flavus) and their toxins are present in maize of preharvest origin in Hungary. Resistance can be an important tool in reducing the infection and toxin contamination from these rots in maize. Previous results identified resistance differences in maize hybrids that were suitable for use in evaluating their risk from toxigenic fungi and their toxins. During the tests, two methodical improvements were achieved: the use of three isolates of the fungus secured and a more precise estimation of resistance to ear rots and their resistance to toxin accumulation or overproduction. The improvement in sampling and the tests of subsamples made the evaluation for the statistics much more exact. This way, we were able to reduce the Within value, providing a statistically more reliable method of evaluation. Earlier data had confirmed that toxin contamination could not be predicted well from visual ear rot severity data. Contradictory results for hybrid ranking were often identified between isolates. The resistance to disease and toxin contamination is not generally valid. The new suggested methodology compares the performance of hybrids in a large number of epidemic situations to identify adaptable hybrids that can respond to diverse conditions; therefore, the stability of resistance and toxin response is decisive information to evaluate risk analyses. The increased number of disease toxin data allowed for lower LSD 5% values for toxins, a much finer analysis of toxin overproduction and underproduction, and a wider database for stability analyses. This way, we obtained important additional separated information about resistance to accumulation of toxins and about maize resistance to these pathogens that is suitable to provide much more reliable testing than was possible until now. Globally, about 50–100 million metric tons can be saved by excluding susceptible hybrids from commercial production.

AbstractThe acreage of English walnut (Juglans regia L.) is constantly expanding in Hungary, due to the favorable climatic conditions and economic importance. Last years, serious damage was reported from several orchards with high percentage of rotted, moldy kernels. The aim of this research was to identify the pathogens at different growth stages. Fungi were cultured from the spotty, shriveled and rotted kernels, and monosporic isolates were identified based on morphological characters and molecular markers (ITS region and tef1 locus sequences). Botryosphaeria dothidea and Diaporthe eres were identified in high proportion from symptomatic kernels. These species were also isolated from different parts of walnut trees in different seasons. D. eres was detected in a high proportion from asymptomatic buds in March, while the presence of both species was observed in symptomatic husks with Overnight Freezing-Incubation Technique (ONFIT) in June. Their optimal growth temperature defined to be between 20–25 °C, and the growth of D. eres isolates was completely inhibited at 35 °C.

During recent decades there has been an upsurge of studies exploring the nature and conditions of human love. This article examines an original and consciously Christian approach by the Hungarian-French philosopher, Miklos Veto, who builds his innovative account of love on trinitarian foundations (Court traite sur l'amour, L'Harmattan, 2020). His 'expanded' metaphysics lays bare the theological content of philosophical assumptions, and it also rethinks traditional theological themes in a novel conceptual way. Our survey proceeds in three consecutive steps. First, it reflects on the overall shape of Veto's project and on his distinctive view of the relationship between the philosophical and the theological enterprise. Second, it investigates some key concepts of Veto's (uncompleted) philosophy of God and central elements of his conception of divine love. Third, it examines Veto's phenomenological analyses of various forms of human love in order to outline the pivotal building blocks of his novel approach, which, however, provokes further questions and invites one to revitalise both the theological and the philosophical quest for a better understanding of this ceaselessly intriguing topic.

Resistance to toxigenic fungi and their toxins in maize is a highly important research topic, as mean global losses are estimated at about 10% of the yield. Resistance and toxin data of the hybrids are mostly not given, so farmers are not informed about the food safety risks of their grown hybrids. According to the findings aflatoxin regularly occurs at preharvest in Hungary and possibly other countries in the region can be jeopardized. We tested, with an improved methodology (two isolates, three pathogens, and a toxin control), 18 commercial hybrids (2017–2020) for kernel resistance (%), and for toxin contamination separately by two–two isolates of F. graminearum, F. verticillioides (mg/kg), and A. flavus (μg/kg). The preharvest toxin contamination was measured in the controls. Highly significant kernel resistance and toxin content differences were identified between hybrids to the different fungi. Extreme high toxin production was found for each toxic species. Only about 10–15% of the hybrids showed higher resistance to the fungal species tested and lower contamination level of their toxins. The lacking correlations between resistance to different fungi and toxins suggest that resistance to different fungi and response to toxin contamination inherits independently, so a toxin analysis is necessary. For safety risk estimation, separated artificial and natural kernel infection and toxin data are needed against all pathogens. Higher resistance to A. flavus and F. verticillioides stabilizes or improves feed safety in hot and dry summers, balancing the harmful effect of climate changes. Resistance and toxin tests during variety registration is an utmost necessity. The exclusion of susceptible or highly susceptible hybrids from commercial production results in reduced toxin contamination.

Fusarium graminearum and F. culmorum cause the most widespread wheat disease Fusarium head blight (FHB). The present study describes that the Fusarium inoculation of the wheat spikes caused systemic changes in the key elements of the antioxidant/detoxification defence system in the flag leaf during the grain filling period in wheat lines differing in biotic stress susceptibility to explore changes in some components of the response. According to our data, the inoculation with both F. graminearum and F. culmorum at the anthesis changed significantly the activities of superoxide dismutase (SOD) and guaiacol peroxidase (POD) enzymes, as well as the glutathione transferase (GST) activity in the flag leaves of the selected wheat lines approx. two weeks later after the infection. In silico approach supported the expressional up-regulation of various GST genes upon Fusarium infection. Based on our results, GST sequences TaGSTF26 and TaGSTU120 were among the series of important stress response genes, which were transcriptionally up-regulated, thus possibly playing a role in the systemic response to Fusarium infection, where TaGSTF26 might have an important role in the successful defence. These GSTs can serve as effective markers of the detoxification process for breeders and plant protection in the future.

Mycotoxins originating in the preharvest period represent a less studied research problem, even though they are of the utmost practical significance in maize production, determining marketability (within EU limits), and storage ability, competitiveness, and profit rate. In this study, 18–23 commercial hybrids were tested between 2014 and 2021. Natural infection from Fusarium spp. was higher than 1.5%, and for Aspergillus spp. this was normally 0.01% or 0, much lower than would be considered as severe infection. In spite of this, many hybrids provided far higher toxin contamination than regulations allow. The maximum preharvest aflatoxin B1 was in 2020 (at 2286 μg/kg), and, in several cases, the value was higher than 1000 μg/kg. The hybrid differences were large. In Hungary, the presence of field-originated aflatoxin B1 was continuous, with three AFB1 epidemics in the 8 years. The highest DON contamination was in 2014 (at 27 mg/kg), and a detectable DON level was found in every hybrid. FUMB1+B2 were the highest in 2014 (at 45.78 mg/kg). At these low infection levels, correlations between visual symptoms and toxin contaminations were mostly non-significant, so it is not feasible to draw a conclusion about toxin contamination from ear rot coverage alone. The toxin contamination of hybrids for a percentage of visual infection is highly variable, and only toxin data can decide about food safety. Hybrids with no visual symptoms and high AFB1 contamination were also identified. Preharvest control, including breeding and variety registration, is therefore of the utmost importance to all three pathogens. Even natural ear rot and toxin data do not prove differences in resistance, so a high ear rot or toxin contamination level should be considered as a risk factor for hybrids. The toxin control of freshly harvested grain is vital for separating healthy and contaminated lots. In addition, proper growing and storage conditions must be ensured to protect the feed safety of the grain.

Toxigenic potential of four and one isolate of A. alternata and A. tenuissima, respectively, on durum wheat cultivar Dusan (Triticum durum L.) and common wheat cultivar Barbee (T. vulgare L.) were tested. Three different wheat / isolate genotype combinations were used for artificial inoculation of grains under laboratory conditions and toxins production. Alternaria toxins alternariol (AOH), alternariol monomethyl ether (AME), tentoxin (TEN), tenuazonic acid (TeA) and altenuen (ALT) concentrations were determined by LC-MS/MS. Cultivar Barbee proved to be a more suitable substrate for toxin production, whereby AOH, AME and TeA were present in highest concentrations. These results underline the possibility of fungal infection and mycotoxin production by Alternaria species in field and under storage conditions. Further research is needed for official regulation of ac?ceptable levels of Alternaria mycotoxins in food and feed.

Thermogenic brown and beige adipocytes might open up new strategies in combating obesity. Recent studies in rodents and humans have indicated that these adipocytes release cytokines, termed "batokines". Irisin was discovered as a polypeptide regulator of beige adipocytes released by myocytes, primarily during exercise. We performed global RNA sequencing on adipocytes derived from human subcutaneous and deep-neck precursors, which were differentiated in the presence or absence of irisin. Irisin did not exert an effect on the expression of characteristic thermogenic genes, while upregulated genes belonging to various cytokine signaling pathways. Out of the several upregulated cytokines, CXCL1, the highest upregulated, was released throughout the entire differentiation period, and predominantly by differentiated adipocytes. Deep-neck area tissue biopsies also showed a significant release of CXCL1 during 24 h irisin treatment. Gene expression data indicated upregulation of the NFκB pathway upon irisin treatment, which was validated by an increase of p50 and decrease of IκBα protein level, respectively. Continuous blocking of the NFκB pathway, using a cell permeable inhibitor of NFκB nuclear translocation, significantly reduced CXCL1 release. The released CXCL1 exerted a positive effect on the adhesion of endothelial cells. Together, our findings demonstrate that irisin stimulates the release of a novel adipokine, CXCL1, via upregulation of NFκB pathway in neck area derived adipocytes, which might play an important role in improving tissue vascularization.

Gibberella ear rot (GER) is an important fungal ear pathogen of maize that causes ear rot and toxin contamination. Most previous works have only dealt with the visual symptoms, but not with the toxins of GER. As food and feed safety rankings depend on toxin contamination, including deoxynivalenol (DON), without toxins, nothing can be said about the risks involved in food and feed quality. Therefore, three susceptible, three medium-susceptible, and three medium-resistant mother lines were crossed with three testers with differing degrees of resistance and tested between 2017–2020. Two plot replicates and two fungal strains were used separately. The highest heterosis was found at the GER% with a 13% increase across 27 hybrids, including 7 hybrids showing negative heterosis (a higher hybrid performance above the parental mean), with a variance ranging between 63.5 and −55.4. For DON, the mean heterosis was negative at −35%, and only 10 of the 27 hybrids showed a positive heterosis. The mean heterosis for DON contamination, at 1% GER, was again negative (−19.6%, varying between 85% and 224%). Only 17 hybrids showed heterosis, while that of the other 17 was rated higher than the parental mean. A positive significant correlation was found only for GER% and DON; the other factors were not significant. Seven hybrids were identified with positive (2) or negative (5) heterosis for all traits, while the rest varied. For DON and GER, only 13 provided identical (positive or negative) heteroses. The majority of the hybrids appeared to diverge in the regulation of the three traits. The stability of GER and DON (variance across eight data sets) did not agree—only half of the genotypes responded similarly for the two traits. The genetic background for this trait is unknown, and there was no general agreement between traits. Thus, without toxin analyses, the evaluation of food safety is not possible. The variety in degrees of resistance to toxigenic fungi and resistance to toxin accumulation is an inevitable factor.

Mycotoxin contamination of maize often raises risks for human and animal health. The most frequently detected mycotoxins in maize are trichothecenes, fumonisins, and aflatoxin. A total number of 17,011 maize samples were tested by SGS for their mycotoxin content between 2012 and 2017. The toxin results clearly show that the southern areas of the country had higher levels of toxin contamination than the average. According to the dataset, aflatoxin contamination has become regular but the appearance of fumonisins was also more frequent. Deoxynivalenol toxin accumulation in crops can also reach dangerous levels under favorable ecological conditions. The fluctuation between years and regisons is decisively shaped by the weather conditions. However, the two pathogens with less virulence ( Fusarium verticillioides and Aspergillus flavus ) must be taken into account and the contribution of insect pests. 72.63% of the total fumonisin concentration was defined as fumonisin B 1 , 20.34% as fumonisin B 2 , and 7.03% as fumonisin B 3 . The correlations between the three fumonisins analogs were higly significant ( P = 0.001), and correlation coefficient varied between 0.961 and 0.998 across the six years of evaluation. This is the first complex evaluation of deoxynivalenol, fumonisin, and aflatoxin contamination of maize samples in Hungary.

Aspergillus strains were isolated from Hungarian mills in order to get information on the appearance of sterigmatocystin (ST) producing moulds, whose presence has never been demonstrated in Hungary. Fungal isolates were classified into nine morphotypes, sections Nigri , Nidulantes , Versicolores (two morphotypes), Circumdati , Flavi (two morphotypes), Clavati and Terrei by classical mycological assays. ST producing strains could be classified into section Versicolores . ST production of the isolates was assessed by liquid and solid phase growth experiments and compared to ST producing reference strains: Aspergillus pepii SzMC 22332, Aspergillus versicolor SzMC 22333, Aspergillus griseoaurantiacus SzMC 22334 and Aspergillus nidulans RDIT9.32. Four of our isolates marked as Km11, Km14, Km26 and Km31 showed ST production in liquid medium. ST production on solid phase corn grit substrate was measured after three weeks of incubation, and Km26 isolate proved to be the most prominent with a toxin concentration of 277.1 μg g −1 , surpassing all reference strains. The toxin-producing ability of Km26 isolate was also tested in a field experiment, where corn was infected. By the end of the experiment, ST level of 19.56 μg kg −1 was measured in infected corn. Molecular taxonomic identification of the Km26 strain was performed using internal transcribed spacer (ITS), calmodulin and tubulin sequence analyses. Based on these studies, strain Km26 was identified as Aspergillus creber . Here we report that an ST-producing A. creber strain has appeared in Hungary, and the Km26 strain is the first known extreme ST-producing mould in this country. As a result of climate change, aflatoxin B1 producing Aspergillus flavus strains have appeared in Hungary in the last decade. As strain Km26 is the only A. creber isolate in Hungary so far, there is no sign of mass prevalence, and due to the lower temperature optimum of the species compared to A. flavus , its appearance is probably not related to climate change.

Fusarium head blight (FHB), primarily caused by a fungal plant pathogen Fusarium graminearum, is a devastating disease of wheat and other cereals. FHB reduces yield, but also the quality and feeding value of the crop. The fungus produces the mycotoxin deoxynivalenol (DON) that poses a significant threat to the health of domestic animals and humans. In 2019 Fusarium epidemic occurred not only the southern and eastern parts of Hungary, but affected other area of Central Europe. The mycotoxin patterns varied tremendously, depending on the geographic area, different resistance levels of wheat genotypes, weather and soil conditions and cropping factors. In this survey 192 samples of different bread wheat (Triticum aestivum L.) genotypes from three geographically different regions were tested for DON toxin contamination by HPLC-MS method. Average levels of mycotoxin contamination 3.80 mg/kg; it is three times higher than the European maximum limit for unprocessed cereals intended for human consumption. The content range is very wide (0.15 – 20.71 mg/kg), 76% of the samples exceeded the EU risk threshold level.

Brown and beige adipocytes dissipate energy by uncoupling protein 1 (UCP1)‐dependent and UCP1‐independent thermogenesis, which may be utilized to develop treatments against obesity. We have found that mRNA and protein expression of the alanine/serine/cysteine transporter‐1 (ASC‐1) was induced during adipocyte differentiation of human brown‐prone deep neck and beige‐competent subcutaneous neck progenitors, and SGBS preadipocytes. cAMP stimulation of differentiated adipocytes led to elevated uptake of serine, cysteine, and glycine, in parallel with increased oxygen consumption, augmented UCP1‐dependent proton leak, increased creatine‐driven substrate cycle‐coupled respiration, and upregulation of thermogenesis marker genes and several respiratory complex subunits; these outcomes were impeded in the presence of the specific ASC‐1 inhibitor, BMS‐466442. Our data suggest that ASC‐1‐dependent consumption of serine, cysteine, and glycine is required for efficient thermogenic stimulation of human adipocytes.

BACKGROUND:Recently, ProFAT and BATLAS studies identified brown and white adipocytes marker genes based on analysis of large databases. They offered scores to determine the thermogenic status of adipocytes using the gene-expression data of these markers. In this work, we investigated the functional context of these genes.RESULTS:Gene Set Enrichment Analyses (KEGG, Reactome) of the BATLAS and ProFAT marker-genes identified pathways deterministic in the formation of brown and white adipocytes. The collection of the annotated proteins of the defined pathways resulted in expanded white and brown characteristic protein-sets, which theoretically contain all functional proteins that could be involved in the formation of adipocytes. Based on our previously obtained RNA-seq data, we visualized the expression profile of these proteins coding genes and found patterns consistent with the two adipocyte phenotypes. The trajectory of the regulatory processes could be outlined by the transcriptional profile of progenitor and differentiated adipocytes, highlighting the importance of suppression processes in browning. Protein interaction network-based functional genomics by STRING, Cytoscape and R-Igraph platforms revealed that different biological processes shape the brown and white adipocytes and highlighted key regulatory elements and modules including GAPDH-CS, DECR1, SOD2, IL6, HRAS, MTOR, INS-AKT, ERBB2 and 4-NFKB, and SLIT-ROBO-MAPK. To assess the potential role of a particular protein in shaping adipocytes, we assigned interaction network location-based scores (betweenness centrality, number of bridges) to them and created a freely accessible platform, the AdipoNET ( https//adiponet.com ), to conveniently use these data. The Eukaryote Promoter Database predicted the response elements in the UCP1 promoter for the identified, potentially important transcription factors (HIF1A, MYC, REL, PPARG, TP53, AR, RUNX, and FoxO1).CONCLUSION:Our integrative approach-based results allowed us to investigate potential regulatory elements of thermogenesis in adipose tissue. The analyses revealed that some unique biological processes form the brown and white adipocyte phenotypes, which presumes the existence of the transitional states. The data also suggests that the two phenotypes are not mutually exclusive, and differentiation of thermogenic adipocyte requires induction of browning as well as repressions of whitening. The recognition of these simultaneous actions and the identified regulatory modules can open new direction in obesity research.

White adipocytes contribute to energy storage, accumulating lipid droplets, whereas brown and beige adipocytes mainly function in dissipating energy as heat primarily via the action of uncoupling protein 1 (UCP1). Bone morphogenic protein 7 (BMP7) was shown to drive brown adipocyte differentiation in murine interscapular adipose tissue. Here, we performed global RNA-sequencing and functional assays on adipocytes obtained from subcutaneous (SC) and deep-neck (DN) depots of human neck and differentiated with or without BMP7. We found that BMP7 did not influence differentiation but upregulated browning markers, including UCP1 mRNA and protein in SC and DN derived adipocytes. BMP7 also enhanced mitochondrial DNA content, levels of oxidative phosphorylation complex subunits, along with PGC1α and p-CREB upregulation, and fragmentation of mitochondria. Furthermore, both UCP1-dependent proton leak and UCP1-independent, creatine-driven substrate cycle coupled thermogenesis were augmented upon BMP7 addition. The gene expression analysis also shed light on the possible role of genes unrelated to thermogenesis thus far, including ACAN, CRYAB, and ID1, which were among the highest upregulated ones by BMP7 treatment in both types of adipocytes. Together, our study shows that BMP7 strongly upregulates thermogenesis in human neck area derived adipocytes, along with genes, which might have a supporting role in energy expenditure.