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From Activation to Inactivation: Computational Investigation of Lytic Polysaccharide Monooxygenase Mechanisms
No full textLytiske polysaccharidmonooxygenaser (LPMO’er) er kobberafhængige enzymer, der fremmer nedbrydningen af ellers svært nedbrydelige polysaccharider via. oxidativ kemi. Derved spiller LPMO’er en central rolle i omdannelsen af lignocellulosisk biomasse til biobrændstof. På trods af deres industrielle relevans er flere mekanistiske aspekter af LPMO-katalyse endnu uafklarede. Denne afhandling adresserer disse åbne spørgsmål, primært ved hjælp af ‘quantum mechanics/molecular mechanics’ (QM/MM) metoder.Den første del af arbejdet fokuserer på identiteten og aktiveringsmekanismerne for LPMO’ens co-substrat. Ved at anvende udvidede QM-regioner vises det, at hydrogenperoxid (H2O2 ) snarere end molekylært ilt (O2 ) er det katalytisk relevante co-substrat i LPMO’en fra Lentinus similis (LsAA9A): Dannelsen af et reaktivt [CuO]+ via H2O2 er både termodynamisk og kinetisk muligt, i modsætning til den O2 -baserede reaktionsvej. I modsætning til tidligere teoretiske studier, der understøttede begge mekanismer, stemmer disse resultater overens med nyere eksperimentelle fund. En opfølgende undersøgelse fokuserede på betydningen af enzymets dynamik under reaktionen mellem [CuO]+ og substratet. Simuleringer med klassisk molekylær dynamik (MD) og QM/MM-beregninger viser, at barriererne for denne reaktion varierer markant afhængigt af substratets positionering, hvilket understreger betydningen af strukturel dynamik for reaktiviteten og forklarer uoverensstemmelser i tidligere beregningsstudier. Den anden del af arbejdet omhandler LPMO’ers inaktivering pga. oxidation af den kobberkoordinerende histidin. Vores QM/MM beregninger viser, at det reaktive [CuO]+-intermediat kan forårsage histidinoxidation. En kendt post-translationel methylering af His1 (som ofte ses i LPMO’er fra svampe) øger moderat reaktionsbarrieren for oxidation af den kobberkoordinerende histidin, hvilket indikerer en potentiel beskyttende effekt. Derudover foreslås det, at en konserveret tyrosin tæt på det aktive site deltager i en beskyttelsesmekanisme ved at danne et radikal, der forhindrer skade på de kobberkoordinerende histidiner. Undersøgelser af to forskellige LPMO’er viser, at dannelsen af tyrosylradikaler er væsentligt mere favorabel end histidinoxidation, uanset hvilken LPMO vi ser på; dette er i overensstemmelse med nyere eksperimentelle resultater, der viser, at LPMO’er uden dette tyrosin er mere tilbøjelige til inaktivering. Samlet set giver disse studier værdifuld mekanistisk indsigt i både produktive og inaktiverende reaktioner i LPMO’er og understreger den afgørende betydning af præcise beregningsmetoder for forståelsen af enzymkatalyse.Lytic polysaccharide monooxygenases (LPMOs) are copper-dependent enzymes that boost the degradation of recalcitrant polysaccharides through oxidative cleavage and play a key role in lignocellulosic biomass conversion into biofuel. Despite their industrial relevance, several mechanistic aspects of LPMO catalysis and self-inactivation remain unresolved. This thesis addresses these open questions, primarily using quantum mechanics/molecular mechanics (QM/MM) methods.The first part of this work focuses on the identity and activation mechanisms of the LPMO co-substrate. By employing extended QM regions and the Big-QM approach, it is shown that hydrogen peroxide (H2O2 ) rather than molecular oxygen (O2 ) is the catalytically relevant co-substrate for substrate oxidation in the LPMO from Lentinus similis (LsAA9A). The formation of the commonly proposed reactive [CuO]+ species via H2O2 is both thermodynamically and kinetically viable, in contrast to the O2 -driven pathway. Unlike previous theoretical studies that supported both mechanisms, these results align with recent experimental findings. The influence of enzyme–substrate conformation on the hydrogen atom abstraction (HAA), which was suggested as the rate-limiting step of the substrate oxidation reaction, was investigated in a follow-up study. Classical molecular dynamics (MD) simulations in combination with QM/MM calculations reveal that HAA barriers vary strongly with substrate positioning, emphasising the role of structural dynamics in determining reactivity and explaining discrepancies in previous computational studies.The second part of this work focuses on LPMO self-oxidation, particularly of the coppercoordinating histidine brace. QM/MM calculations show that the highly reactive [CuO]+ intermediate can trigger histidine oxidation, a process known to contribute to enzyme self-inactivation. Post-translational methylation of His1, commonly found in fungal LPMOs, moderately increases the barrier for this reaction, indicating a potential protective effect. Additionally, a conserved active-site tyrosine is proposed to participate in a protective mechanism by forming a tyrosyl radical, which may help prevent oxidative damage to critical catalytic residues. Investigations on two different LPMOs demonstrate that tyrosyl radical formation is significantly more favourable than histidine oxidation, aligning with recent experimental findings showing that LPMOs lacking this tyrosine are more prone to self-oxidation.Together, these studies offer valuable mechanistic insights into both the productive and self-damaging chemistry of LPMOs, emphasising the critical role of accurate computational modeling in understanding enzyme catalysis
Public service users’ responses to performance information:Bayesian learning or motivated reasoning?
No full textAlthough performance information is widely promoted to improve the accountability of public service provision, behavioral research has revealed that motivated reasoning leads recipients to update their beliefs inaccurately. However, the reasoning processes of service users have been largely neglected. We develop a theory of public service users' motivated reasoning about performance information stemming from their identification with the organization providing their services. We address a significant challenge to studying motivated reasoning - that widely used existing research designs cannot rule out alternative cognitive explanations, especially Bayesian learning, such that existing findings could be driven by strong prior beliefs rather than biased processing of new information. We use a research design incorporating Bayesian learning as a benchmark to identify departures from accuracy motivated reasoning process. We assess the empirical implications of the theory using a preregistered information provision experiment among parents with children using public schools. To assess their identity-based motivated reasoning, we provide them with noisy, but true, performance information about their school. Overall, we find no evidence of directionally motivated reasoning. Instead, parents change their beliefs in response to performance feedback in a way that largely reflects conservative Bayesian learning. Performance reporting to service users is less vulnerable to motivational biases in this context than suggested by the general literature on motivated reasoning. Furthermore, exploratory findings show that performance information can correct erroneous beliefs among misinformed service users, suggesting that investment in reporting performance to service users is worthwhile to inform their beliefs and improve accountability.</p
Assembling intelligence in United Nations peacekeeping: between transformation and path dependency
No full textThis article traces the evolution of intelligence in United Nations peacekeeping through a practice-based assemblage lens. We address a gap in the literature by transcending the focus on 'peacekeeping intelligence' as merely an evolving policy instrument. Instead, we employ an 'analytic of assemblage' that reveals the intrinsic ambiguity of both the concept of peacekeeping intelligence, and the related competing perspectives as well as forms of expertise among stakeholders. We select the United Nations Operation in the Congo (ONUC, 1960-1964), the United Nations Stabilization Mission in Haiti (MINUSTAH, 2004-2017), and the United Nations Multidimensional Integrated Stabilization Mission in Mali (MINUSMA, 2013-2023) as cases to reconstruct the historical evolution of intelligence within peacekeeping. Our analysis reveals profound tensions between efforts to transform intelligence for broader goals like the protection of civilians, on the one hand, and the persistent dominance of military knowledge and tactical priorities in its implementation, on the other. We convey the enduring predominance of military priorities shaping intelligence practices across spatio-temporal contexts, grounded in historical legacies of doctrinal developments, training and regional collaborations. The analysis thereby highlights the interplay between contingency and the influence of enduring power structures in shaping the evolving peacekeeping assemblage. This offers a perspective that links assemblage approaches with the analysis of not only emergence but also path dependency influenced by historical and geopolitical contexts and suggests that strengthening such analytical link holds wider potential for advancing contributions of assemblage approaches to critical security studies.</p
Two-dimensional MXenes:A route from synthesis to applications in self-powered IoT devices
No full textIn recent times, self-powered autonomous electronic devices, equipped with energy scavenging from ambient sources, have surged in portable and wearable electronics due to their compact multifunctional nature. The discovery of two-dimensional MXene materials further revolutionizes energy harvesting and conversion with distinctive optoelectronic, electrochemical, and mechanical properties. MXenes show significant promise in enhancing the performance, durability, and versatility of IoT devices, providing advantages over other two-dimensional materials in terms of conductivity, surface area, chemical stability, fabrication simplicity, compatibility, and biocompatibility. This review contextualizes the preparation and synthesis routes of MXene together with its symbiotic contribution to harnessing energy from available sources in the environment. Commencing with an in-depth analysis of the synthesis approaches and their tailored characteristics of MXene for energy capture, the study subsequently delves into the synergistic role of MXene across diverse energy sources, encompassing solar, triboelectric, thermoelectric, piezoelectric, salinity-gradient, and electrokinetic. Ultimately, the review underscores imminent challenges and prospects, envisioning the complete harnessing of MXene's potential in energy harvesting. This succinct review is anticipated to enhance comprehension of MXene and its composites, thus paving the way for pioneering MXene material innovations and processing techniques in energy harvesting advancement.</p
Sustainability Discourses in the Leadership and Management Literature: A Critical Review
No full textThis review advances a critical discussion of prevalent sustainability discourses in the leadership and management literature. Since the 1990s, ecocentric approaches to management have been discussed in opposition to anthropocentric (human centered) management theory. However, limited attention has been given, so far, to clarifying how sustainability discourses have influenced the literature of leadership and management. The influence of rights-based United Nations Sustainable Development dating back to the Brundtland report in 1987 is widely recognized, as are business and technology-based discourses in sustainability (ecological modernism). Such discourses are united in a belief in green growth. However, a literature review shows that critical sustainability discourses about limits to growth, planetary boundaries and the need for degrowth, as well as ecocentric discourses, are only marginally present in the literature on leadership and management. In view of the need for leadership to address the “polycrisis” of entangled environmental and social crises, we problematize the lack of critical sustainability discourses in the leadership and management literature.</p
Relink Programmes:Impact of Reengagement on Linkage to Care Across 82 006 People With Hepatitis C
No full textBACKGROUND AND AIMS: A major barrier to hepatitis C virus (HCV) elimination is the failure to ensure that individuals complete the HCV care cascade after they test positive for HCV RNA and/or antibody. Microelimination programmes support protocols that reengage patients with care/treatment. We describe 18 microelimination programmes aimed at identifying persons who were diagnosed but untreated/not cured and reconnecting them to care. Here, we report the programmes' effectiveness, identify key challenges and suggest best practices for future initiatives.METHODS: Pooled and individual programme data (available as of 31 January 2024) were assessed. Each programme had a retrospective phase in which medical/laboratory records were searched within a specified date range for patients who were positive for HCV antibody and/or RNA at last testing. In a prospective phase, programmes attempted to reengage these patients with care.RESULTS: Across the 18 programmes worldwide, 82 006 individuals were identified as eligible for follow-up. Overall, 21 235 people were selected for attempted contact, and 5308 were relinked to care. In 17 programmes reporting treatment data, 51% (1513 of 2976) of relinked patients initiated treatment. Four programmes used innovative care models and achieved treatment initiation rates ≥ 80%. Amongst patients with results available, 89% (643 of 722) who initiated treatment achieved HCV cure. Challenges included the inability to contact people and missed appointments.CONCLUSION: Systematic screening of medical/laboratory records was effective in identifying patients who had been lost to follow-up, and the use of innovative care models, such as test-and-treat or decentralised approaches, resulted in higher treatment numbers.</p
Fibrinogen in individuals with obesity and steatotic liver disease
No full textBaggrund: Fedme er stigende på verdensplan og er forbundet med en række affølgesygdomme. Den hepatiske manifestation af fedme er metaboliskdysfunktionsassocieret steatotisk leversygdom (MASLD), som opstår som følge affedtophobning, der skader hepatocytterne. MASLD har et bredt sygdomsspektrum, derspænder fra simpel steatose til metabolisk dysfunktionsassocieret steatohepatitis (MASH). I de mere fremskredne stadier udvikles fibrose, som potentielt kan føre til cirrose oghepatocellulært karcinom. Studier i mus har vist, at en variation i koagulationskaskadensnøgleprotein, fibrinogen, er forbundet med udviklingen af fedme og MASLD baseret på enkronisk lav grad af inflammation, hvor fibrinogen interagerer med leukocytter og fibrin(ogen)aflejres i væv. Det er ukendt, hvordan naturligt forekommende fibrinogenvarianter samtdannelsen af fibrin i plasma og væv er relateret til fedme og MASLD hos mennesker.Formål: At udvikle en præcis og sensitiv metode (ELISA, enzyme-linked immunosorbent assay) til måling af humant fibrinogen γ’. At undersøge, i et klinisk studie, hvordan plasmaniveauer af fibrinogen γ’ og to andre fibrinogenvarianter (fibrinogen αE og sialyleret fibrinogen) sammen med egenskaber af ex vivo dannede fibrinclots og fibrindannelse ilevervæv er associeret med sværhedsgraden af fedme, MASLD og fibrose. Desuden varformålet at undersøge ændringer i fibrinogenvarianter og fibrinmålinger to år efter bariatriskkirurgi sammenlignet med en ikke-kirurgisk kontrolgruppe.Hypotese: Plasmaniveauer af fibrinogenvarianter samt fibrinclottets egenskaber ogfibrinaflejringer i levervæv er associeret med sværhedsgraden af fedme og MASLD, og dissevariable ændres signifikant to år efter bariatrisk kirurgi som udtryk for metabolisk oginflammatorisk forbedring.Metoder: Til udviklingen af fibrinogen γ’ ELISA blev der genereret musemonoklonaleantistoffer specifikt rettet mod den C-terminale del af fibrinogen γ’. Assayet blev valideretmed hensyn til nøjagtighed, sensitivitet og præcision. I det kliniske studie blev 195 personermed BMI>35 kg/m2inkluderet, hvoraf en undergruppe på 93 personer enten gennemgikbariatrisk kirurgi (n=35) eller fungerede som ikke-kirurgisk kontrolgruppe (n=58) og blev fulgt i to år. Blodprøver og leverbiopsier blev indsamlet ved baseline og to år efter kirurgi (kirurgisk gruppe) eller ca. 2,5 år efter baseline (kontrolgruppe). Derudover blev derindsamlet blodprøver fra en normalvægtig referencegruppe bestående af 120 raskebloddonorer. Fibrinogenvarianter blev målt i plasma ved hjælp af ELISA, og fibrinclottenesegenskaber blev undersøgt ved turbiditet. Sværhedsgraden af MASLD og fibrose blevvurderet ud fra levervævsprøverne, og hos tre personer med meget forskellig BMI blevvævsprøverne immunhistokemisk farvet for fibrin med et monoklonalt fibrinspecifiktantistof.Resultater: Der blev produceret specifikke monoklonale antistoffer mod fibrinogen γ’, som blev implementeret i ELISA’en. Præcision af fibrinogen γ’ ELISA var 7%. Absolutte niveauer affibrinogenvarianter (fibrinogen γ’, fibrinogen αE og sialyleret fibrinogen) samt fibrinclotegenskaber som Vmax, fiberdiameter, og maksimal absorbans (MA) var højere hos personer med et BMI>45 kg/m2 sammenlignet med personer med et BMI<40 kg/m2, mens det modsatte blev observeret for fibrinclottets lyse og fiberdensitet. Absolutte og relative niveauer af fibrinogen αE steg med sværhedsgraden af MASLD, mens Vmax, fiberdiameter og MA var lavere hos personer med MASH sammenlignet med personer uden MASLD. Absolutte og relative niveauer af fibrinogen γ’ faldt med stigende sværhedsgrad af fibrose. Efter bariatrisk kirurgi var niveauerne af sialyleret fibrinogen, Vmax, fiberdiameter og MA lavere, mens relative niveauer af fibrinogenvarianter, fibrinclottets lyse og fiberdensitet var højere sammenlignet med kontrolgruppen. Intensiteten af fibrinfarvning i levervævsprøverne var stigende med sværhedsgraden af fedme, men der var ingen sammenhæng med graden af MASLD og ikke en klar tendens til faldende intensitet efter bariatrisk kirurgi. Absolutte niveauer af alle tre fibrinogenvarianter, relative niveauer af sialyleret fibrinogen samt fibrinclotegenskaberne Vmax, fiberdiameter og MA var højere hos personer med fedme sammenlignet med normalvægtige bloddonorer. Relative niveauer af fibrinogen γ’ og fibrinogen αE, fibrinclottets lyse og fiberdensitet var lavere i fedmegruppen.Konklusion: Der blev udviklet en præcis og sensitiv ELISA til måling af fibrinogen γ’. Fedme og MASLD ændrer profilerne for fibrinogenvarianter og fibrindannelse, hvilket antyder, at disse biomarkører enten afspejler sygdommens sværhedsgrad eller spiller en mekanistisk rolle i udviklingen af fedme og MASLD.Background: Obesity is increasing worldwide and is associated with several comorbidities. The hepatic manifestation of obesity is metabolic dysfunction-associated steatotic liver disease (MASLD), which is a consequence of fat accumulation causing damage tohepatocytes. MASLD has a broad disease spectrum from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH). In the more advanced stages, fibrosis develops, which might eventually lead to cirrhosis and hepatocellular carcinoma. Studies in mice link variations of the key protein of the coagulation cascade, fibrinogen, to the development of obesity and MASLD based on low-grade inflammation involving interaction of fibrinogen with leukocytes and tissue fibrin(ogen) depositions. It is unknown how naturally occurring fibrinogen variants and plasma and tissue fibrin formation associate with obesity and MASLD in humans.Objectives: To develop a precise and sensitive enzyme-linked immunosorbent assay (ELISA) for human fibrinogen γ’ and to investigate, in a clinical study, how plasma levels of fibrinogen γ’ and two other fibrinogen variants (fibrinogen αE and sialylated fibrinogen)together with plasma fibrin clot characteristics and hepatic tissue fibrin formation associate with obesity, MASLD, and fibrosis severity. Further, to examine changes in fibrinogen variants and fibrin measures 2 years after bariatric surgery compared to the results in a nonsurgical control group.Hypothesis: The hypothesis is that plasma levels of fibrinogen variants, as well as plasma fibrin clot characteristics and hepatic tissue fibrin deposition, are associated with the severity of obesity and MASLD, and that these variables undergo significant changes 2 years after bariatric surgery, reflecting metabolic and inflammatory restoration.Methods: For the development of the fibrinogen γ’ ELISA, C-terminal fibrinogen γ’ specific mouse monoclonal antibodies were generated. Validation of the assay included measures of accuracy, sensitivity, and precision. In the clinical study, we included 195 individuals with a BMI>35 kg/m2, from which a subgroup of 93 individuals, who either underwent bariatric surgery (n=35) or served as a non-surgical control group (n=58), were followed for 2 years. Blood samples and liver biopsies were obtained at baseline and 2 years post-surgery (surgerygroup) or approximately 2.5 years after baseline examination (control group). Further, bloodsamples were obtained from a normal-weight reference group consisting of 120 healthyblood donors. Fibrinogen variants were measured in plasma using ELISAs, and plasma fibrinclot characteristics were studied by turbidity. Hepatic tissue samples were scored for MASLDand fibrosis severity, and in a pilot study of three individuals who differed greatly in BMI, thetissue samples were immunohistochemically stained for fibrin using a monoclonal fibrin-specific antibody.Results: Highly specific fibrinogen γ’ monoclonal antibodies were produced and applied inthe fibrinogen γ’ ELISA. Precision of the fibrinogen γ’ assay was 7%. Absolute levels offibrinogen variants (fibrinogen γ’, fibrinogen αE, and sialylated fibrinogen) and the plasma fibrin clot characteristics Vmax, fiber diameter, and maximum absorbance (MA) were higher in individuals with a BMI>45 kg/m2 compared to individuals with a BMI<40 kg/m2, while the opposite was observed for clot lysis and fiber density. Absolute and relative levels of fibrinogen αE increased with the MASLD severity, whereas Vmax, fiber diameter, and MA were lower in individuals with MASH compared to individuals with no MASLD. Absolute and relative levels of fibrinogen γ’ decreased with the severity of fibrosis. After bariatric surgery, sialylated fibrinogen levels, Vmax, fiber diameter, and MA were lower, while relative levels of fibrinogen variants, clot lysis, and fiber density were higher compared with the control group. The intensity of fibrin staining in hepatic tissue samples increased with obesity severity, but was not clearly associated with MASLD or reduced after bariatric surgery and the accompanying weight loss. Absolute levels of all three fibrinogen variants, relative levels of sialylated fibrinogen, and the fibrin clot characteristics Vmax, fiber diameter, and MA were all higher in individuals with obesity compared to the normal-weight blood donors. Relative levels of fibrinogen γ’ and fibrinogen αE, clot lysis, and fiber density were lower in the obesity cohort.Conclusions: A precise and sensitive ELISA was developed for fibrinogen γ’. Obesity and MASLD alter fibrinogen variant and fibrin formation profiles suggesting that fibrinogen variants and fibrin formation serve as biomarkers for severity of metabolic disease or are mechanistically involved in the development of obesity and MASLD
Shifting responsibility to the workers –interpretations of work environment regulation in Greenlandic companies
Full text linkHow do managers and workers make sense of reflexive work environment regulation with relatively abstract formulation of duties for risk assessment and division of responsibility? This question is little studied in research and we contribute to the answer by examining responses to work environment regulation in Greenland. The country is undergoing rapid modernization with a transition from a culture rooted in hunting and fishing to one based on salaried employment. A key milestone in this process is the establishment of Greenlandic Self-Government but work environment regulation remains under Danish jurisdiction. Consequently, companies in Greenland face the challenge of implementing legislation developed for the Danish labour market. We have through in depth case studies investigated how Greenlandic managers and workers interpret the reflexive regulatory requirements for risk assessment and employer responsibility. The results show that they tend to minimize risk and consider the responsibility rather opaque. Managers shift responsibility to workers when they delegate work tasks, and the workers accept this responsibility. Subsequently, if an accidents do occur, workers attribute the accidents to their own failed behaviour. In an era of increasing globalization and growing political pressure for regulation, the implications of this study extend beyond Greenland by showing the constraints for implementation of requirements from the reflexive regulation dominating Europe. We expect similar sensemaking challenges to be present in other resource constrained contexts. For practice the study indicates the need for regulators and employers to tailor work environment regulation and management to the specific labour market and cultural context
Challenges in Revealing Readable Text from Fragments Hidden in Book Bindings:A Case Study from the Herlufsholm Collection
No full textManuscript fragments repurposed in book bindings contain valuable historical text, yet reading these hidden texts presents significant challenges. Multispectral and hyperspectral imaging (MSI and HSI), followed by spectral unmixing, are commonly used to enhance text visibility. However, additional layers of paper make the recovery process particularly difficult. The resulting text images are often blurry and unrecognizable to both human experts and Optical Character Recognition (OCR) systems. Furthermore, the problem is compounded by the lack of sufficient representative data for training deep learning-based restoration models. In this paper, we systematically examine the challenges of recovering readable text images from bookbinding fragments, with a focus on fragments on Herlufsholm 24.1 as a case study. These fragments are part of the Herlufsholm Collection at the University Library of Southern Denmark. We begin with a comparative analysis of MSI and HSI to evaluate their effectiveness in revealing text, highlighting their respective advantages and limitations. To assess the impact of overlaid materials, we conduct a controlled experiment using artificial samples, capturing hyperspectral images of both covered and uncovered text. Additionally, we analyze blur maps to investigate whether the observed blurriness is uniform and whether common models, such as Gaussian blur, adequately represent it. Finally, we explore the effectiveness of existing deblurring models, identifying key limitations, and discussing potential strategies for improving text readability. This study provides a structured analysis of the obstacles at each stage of the process, from imaging to post-processing and deblurring, offering insight into the best practice for recovering text hidden in bindings
BMAL2 controls adipose tissue inflammation and metabolic adaptation during obesity
Full text linkContemporary lifestyle modifications such as changes in nutritional and sleep/wake rhythms increase the risk of metabolic and inflammatory complications linked to obesity, including type 2 diabetes (T2D) and metabolic dysfunction-associated steatohepatitis (MASH). BMAL2 (Brain and Muscle ARNT Like Protein 2) is a transcription factor belonging to the circadian clock transcriptional feedback loop which synchronizes internal biological rhythms to environment. In humans, reduced expression in white adipose tissue (WAT) and specific polymorphisms of BMAL2 are associated with obesity and T2D. In this study we report that Bmal2 deletion in mice leads to increased body weight gain during diet-induced obesity. Loss of BMAL2 triggers the inflammatory response by increasing Tnfα expression and modifying adipocyte progenitor fate. This results in reduced lipid storage capacity within the WAT and increased ectopic storage in the liver. These functional and structural alterations culminate in the onset of hepatic steatosis and insulin resistance in liver and WAT. Overall, our investigations underscore the role of BMAL2 in the development and function of adipocytes, as well as in their inflammatory potential within the WAT. Our findings contribute to the understanding of the role of circadian clock genes in obesity and interconnected metabolic complications.</p