Hepatic danger signaling triggers TREM2+ macrophage induction and drives steatohepatitis via MS4A7-dependent inflammasome activation.

Metabolic dysfunction-associated steatohepatitis (MASH), formerly known as nonalcoholic steatohepatitis (NASH), is an advanced stage of metabolic fatty liver disease. The pathogenic mechanisms of MASH center on hepatocyte injury and the ensuing immune response within the liver microenvironment. Recent work has implicated TREM2+ macrophages in various disease conditions, and substantial induction of TREM2+ NASH-associated macrophages (NAMs) serves as a hallmark of metabolic liver disease. Despite this, the mechanisms through which NAMs contribute to MASH pathogenesis remain poorly understood. Here, we identify membrane-spanning 4-domains a7 (MS4A7) as a NAM-specific pathogenic factor that exacerbates MASH progression in mice. Hepatic MS4A7 expression was strongly induced in mouse and human MASH and associated with the severity of liver injury. Whole-body and myeloid-specific ablation of Ms4a7 alleviated diet-induced MASH pathologies in male mice. We demonstrate that exposure to lipid droplets (LDs), released upon injury of steatotic hepatocytes, triggered NAM induction and exacerbated MASH-associated liver injury in an MS4A7-dependent manner. Mechanistically, MS4A7 drove NLRP3 inflammasome activation via direct physical interaction and shaped disease-associated cell states within the liver microenvironment. This work reveals the LD-MS4A7-NLRP3 inflammasome axis as a pathogenic driver of MASH progression and provides insights into the role of TREM2+ macrophages in disease pathogenesis.

Simultaneous Determination of One-Carbon Folate Metabolites and One-Carbon-Related Amino Acids in Biological Samples Using a UHPLC-MS/MS Method.

One-carbon folate metabolites and one-carbon-related amino acids play an important role in human physiology, and their detection in biological samples is essential. However, poor stability as well as low concentrations and occurrence in different species in various biological samples make their quantification very challenging. The aim of this study was to develop a simple, fast, and sensitive ultra-high-performance liquid chromatography MS/MS (UHPLC-MS/MS) method for the simultaneous quantification of various one-carbon folate metabolites (folic acid (FA), tetrahydrofolic acid (THF), p-aminobenzoyl-L-glutamic acid (pABG), 5-formyltetrahydrofolic acid (5-CHOTHF), 5-methyltetrahydrofolic acid (5-CH3THF), 10-formylfolic acid (10-CHOFA), 5,10-methenyl-5,6,7,8-tetrahydrofolic acid (5,10-CH+-THF), and 4-α-hydroxy-5-methyltetrahydrofolate (hmTHF)) and one-carbon-related amino acids (homocysteine (Hcy), methionine (Met), S-ade-L-homocysteine (SAH), and S-ade-L-methionine (SAM)). The method was standardized and validated by determining the selectivity, carryover, limits of detection, limits of quantitation, linearity, precision, accuracy, recovery, and matrix effects. The extraction methods were optimized with respect to several factors: protease-amylase treatment on embryos, deconjugation time, methanol precipitation, and proteins' isoelectric point precipitation on the folate recovery. Ten one-carbon folate metabolites and four one-carbon-related amino acids were detected using the UHPLC-MS/MS technique in various biological samples. The measured values of folate in human plasma, serum, and whole blood (WB) lay within the concentration range for normal donors. The contents of each analyte in mouse plasma were as follows: pABG (864.0 nmol/L), 5-CH3THF (202.2 nmol/L), hmTHF (122.2 nmol/L), Met (8.63 µmol/L), and SAH (0.06 µmol/L). The concentration of each analyte in mouse embryos were as follows: SAM (1.09 µg/g), SAH (0.13 µg/g), Met (16.5 µg/g), 5,10-CH+THF (74.3 ng/g), pABG (20.6 ng/g), and 5-CH3THF (185.4 ng/g). A simple and rapid sample preparation and UHPLC-MS/MS method was developed and validated for the simultaneous determination of the one-carbon-related folate metabolites and one-carbon-related amino acids in different biological samples.

Myeloid-specific ablation of Basp1 ameliorates diet-induced NASH in mice by attenuating pro-inflammatory signaling.

BACKGROUND AND AIMS: NASH represents a severe stage of fatty liver disease characterized by hepatocyte injury, inflammation, and liver fibrosis. Myeloid-derived innate immune cells, such as macrophages and dendritic cells, play an important role in host defense and disease pathogenesis. Despite this, the nature of transcriptomic reprogramming of myeloid cells in NASH liver and its contribution to disease progression remain incompletely defined. APPROACH AND RESULTS: In this study, we performed bulk and single-cell RNA sequencing (sc-RNA seq) analysis to delineate the landscape of macrophage and dendritic cell transcriptomes in healthy and NASH livers. Our analysis uncovered cell type-specific patterns of transcriptomic reprogramming on diet-induced NASH. We identified brain-abundant membrane-attached signal protein 1 (Basp1) as a myeloid-enriched gene that is markedly induced in mouse and human NASH liver. Myeloid-specific inactivation of Basp1 attenuates the severity of diet-induced NASH pathologies, as shown by reduced hepatocyte injury and liver fibrosis in mice. Mechanistically, cultured macrophages lacking Basp1 exhibited a diminished response to pro-inflammatory stimuli, impaired NLRP3 inflammasome activation, and reduced cytokine secretion. CONCLUSIONS: Together, these findings uncover Basp1 as a critical regulator of myeloid inflammatory signaling that underlies NASH pathogenesis.

Exit wave function reconstruction from two defocus images using neural network.

Wave function reconstruction from one or two defocus images is promising for live atomic resolution imaging in transmission electron microscopy. However, a robust and accurate reconstruction method we still need more attention. Here, we present a neural-network-based wave function reconstruction method, EWR-NN, that enables accurate wave function reconstruction from only two defocus images. Results from both simulated and two different experimental defocus series show that the EWR-NN method has better performance than the widely-used iterative wave function reconstruction (IWFR) method. Influence of image number, defocus deviation, residual image shifts and noise level were considered to validate the performance of EWR-NN under practical conditions. It is seen that these factors will not influence the arrangement of atom columns in the reconstructed phase images, while they can alter the absolute values of all-atom columns and degrade the contrast of the phase images.

Advanced electrocatalytic redox processes for environmental remediation of halogenated organic water pollutants.

Halogenated organic compounds are widespread, and decades of heavy use have resulted in global bioaccumulation and contamination of the environment, including water sources. Here, we introduce the most common halogenated organic water pollutants, their classification by type of halogen (fluorine, chlorine, or bromine), important policies and regulations, main applications, and environmental and human health risks. Remediation techniques are outlined with particular emphasis on carbon-halogen bond strengths. Aqueous advanced redox processes are discussed, highlighting mechanistic details, including electrochemical oxidations and reductions of the water-oxygen system, and thermodynamic potentials, protonation states, and lifetimes of radicals and reactive oxygen species in aqueous electrolytes at different pH conditions. The state of the art of aqueous advanced redox processes for brominated, chlorinated, and fluorinated organic compounds is presented, along with reported mechanisms for aqueous destruction of select PFAS (per- and polyfluoroalkyl substances). Future research directions for aqueous electrocatalytic destruction of organohalogens are identified, emphasizing the crucial need for developing a quantitative mechanistic understanding of degradation pathways, the improvement of analytical detection methods for organohalogens and transient species during advanced redox processes, and the development of new catalysts and processes that are globally scalable.

Antibacterial activity and improvement of the oxidative stability of soybean oil by 4-hydroxybenzyl isothiocyanate from white mustard seeds.

4-Hydroxybenzyl isothiocyanate (4-HBITC) is one of the most important secondary metabolite products in white mustard seeds. The antibacterial activity and inhibition of lipid oxidation of 4-HBITC were investigated. The results indicated that 4-HBITC had a significant antibacterial effect on Escherichia coli, Staphylococcus aureus, and Salmonella typhimurium, and its effect on gram-positive bacteria was superior to that on gram-negative bacteria. The combination of 4-HBITC with citric acid or ascorbic acid had a better antibacterial effect than adding them alone. The antibacterial mechanism of 4-HBITC to affect the metabolic activity rather than the integrity or the permeability of cell membranes was identified. In addition, white mustard seed extract which contains 4-HBITC was found to extend the oxidative stability of soybean oil, and this effect was also improved after the combination of 4-HBITC with citric acid. These results indicated that 4-HBITC and white mustard seed extract have potential for application as a natural preservatives in food and for improving the oxidative stability of edible oils.

Analysis of the Scale of Global Human Needs and Opportunities for Sustainable Catalytic Technologies.

We analyzed the enormous scale of global human needs, their carbon footprint, and how they are connected to energy availability. We established that most challenges related to resource security and sustainability can be solved by providing distributed, affordable, and clean energy. Catalyzed chemical transformations powered by renewable electricity are emerging successor technologies that have the potential to replace fossil fuels without sacrificing the wellbeing of humans. We highlighted the technical, economic, and societal advantages and drawbacks of short- to medium-term decarbonization solutions to gauge their practicability, economic feasibility, and likelihood for widespread acceptance on a global scale. We detailed catalysis solutions that enhance sustainability, along with strategies for catalyst and process development, frontiers, challenges, and limitations, and emphasized the need for planetary stewardship. Electrocatalytic processes enable the production of solar fuels and commodity chemicals that address universal issues of the water, energy and food security nexus, clothing, the building sector, heating and cooling, transportation, information and communication technology, chemicals, consumer goods and services, and healthcare, toward providing global resource security and sustainability and enhancing environmental and social justice. Supplementary Information: The online version contains supplementary material available at 10.1007/s11244-023-01799-3.

Hepatic mitochondrial NAD + transporter SLC25A47 activates AMPKα mediating lipid metabolism and tumorigenesis.

BACKGROUND AIMS: SLC25A47 was initially identified as a mitochondrial HCC-downregulated carrier protein, but its physiological functions and transport substrates are unknown. We aimed to investigate the physiological role of SLC25A47 in hepatic metabolism. APPROACH RESULTS: In the treatment of hepatocytes with metformin, we found that metformin can transcriptionally activate the expression of Slc25a47 , which is required for AMP-activated protein kinase α (AMPKα) phosphorylation. Slc25a47 -deficient mice had increased hepatic lipid content, triglycerides, and cholesterol levels, and we found that Slc25a47 deficiency suppressed AMPKα phosphorylation and led to an increased accumulation of nuclear SREBPs, with elevated fatty acid and cholesterol biosynthetic activities. Conversely, when Slc25a47 was overexpressed in mouse liver, AMPKα was activated and resulted in the inhibition of lipogenesis. Moreover, using a diethylnitrosamine-induced mouse HCC model, we found that the deletion of Slc25a47 promoted HCC tumorigenesis and development through the activated mammalian target of rapamycin cascade. Employing homology modeling of SLC25A47 and virtual screening of the human metabolome database, we demonstrated that NAD + was an endogenous substrate for SLC25A47, and the activity of NAD + -dependent sirtuin 3 declined in Slc25a47 -deficient mice, followed by inactivation of AMPKα. CONCLUSIONS: Our findings reveal that SLC25A47, a hepatocyte-specific mitochondrial NAD + transporter, is one of the pharmacological targets of metformin and regulates lipid homeostasis through AMPKα, and may serve as a potential drug target for treating NAFLD and HCC.

Recurrent Neural Networks for Snapshot Compressive Imaging.

Conventional high-speed and spectral imaging systems are expensive and they usually consume a significant amount of memory and bandwidth to save and transmit the high-dimensional data. By contrast, snapshot compressive imaging (SCI), where multiple sequential frames are coded by different masks and then summed to a single measurement, is a promising idea to use a 2-dimensional camera to capture 3-dimensional scenes. In this paper, we consider the reconstruction problem in SCI, i.e., recovering a series of scenes from a compressed measurement. Specifically, the measurement and modulation masks are fed into our proposed network, dubbed BIdirectional Recurrent Neural networks with Adversarial Training (BIRNAT) to reconstruct the desired frames. BIRNAT employs a deep convolutional neural network with residual blocks and self-attention to reconstruct the first frame, based on which a bidirectional recurrent neural network is utilized to sequentially reconstruct the following frames. Moreover, we build an extended BIRNAT-color algorithm for color videos aiming at joint reconstruction and demosaicing. Extensive results on both video and spectral, simulation and real data from three SCI cameras demonstrate the superior performance of BIRNAT.

Deep learning enabled reflective coded aperture snapshot spectral imaging.

Coded aperture snapshot spectral imaging (CASSI) can acquire rich spatial and spectral information at ultra-high speed, which shows extensive application prospects. CASSI innovatively employed the idea of compressive sensing to capture the spatial-spectral data cube using a monochromatic detector and used reconstruction algorithms to recover the desired spatial-spectral information. Based on the optical design, CASSI currently has two different implementations: single-disperser (SD) CASSI and dual-disperser (DD) CASSI. However, SD-CASSI has poor spatial resolution naturally while DD-CASSI increases size and cost because of the extra prism. In this work, we propose a deep learning-enabled reflective coded aperture snapshot spectral imaging (R-CASSI) system, which uses a mask and a beam splitter to receive the reflected light by utilizing the reflection of the mask. The optical path design of R-CASSI makes the optical system compact, using only one prism as two dispersers. Furthermore, an encoder-decoder structure with 3D convolution kernels is built for the reconstruction, dubbed U-net-3D. The designed U-net-3D network achieves both spatial and spectral consistency, leading to state-of-the-art reconstruction results. The real data is released and can serve as a benchmark dataset to test new reconstruction algorithms.

Employment of cold atmospheric plasma in chilled chicken breasts and the analysis of microbial diversity after the shelf-life storage.

Cold atmospheric plasma, featured as a non-thermal food processing technology has gained prominent attention for its practical application. The demand for chilled chicken has increased rapidly due to its nutritious value. However, chilled chicken often suffers from a short shelf life due to its susceptibility to spoilage. In this study, air- and nitrogen plasma were applied to investigate microbial inactivation effects and shelf-life extension of chilled chicken. Meanwhile, the microbial diversity of chicken breasts after air and nitrogen-CAP treatment and at the end of shelf-life was analyzed. Results illustrated that the inactivation effects of air plasma were more potent than that of nitrogen plasma, while nitrogen plasma could better maintain the sensory properties. Also, further investigation illustrated that air- and nitrogen-CAP could change the microbial community significantly. Both treatment time and working gases were essential experimental parameters that affected the microbial community composition.

Subcellular inactivation mechanisms of Pseudomonas aeruginosa treated by cold atmospheric plasma and application on chicken breasts.

As a novel microbe inactivation strategy, cold atmospheric plasma (CAP) technology has attracted great attractions in the past two decades. This study demonstrated that the CAP treatment was a robust inactivation approach for P. aeruginosa. Air and nitrogen-CAP achieved 100 % inactivation efficiency in 5 and 9 min, respectively. Furthermore, the inactivation mechanisms were explained by measuring several physicochemical indexes, including the characteristics of bacterial suspension, cell membrane integrity, cell viability, and the concentration of intracellular substances. The possible inactivation mechanisms might be that the RONS generated by air and nitrogen attacked the cell envelope, resulted in the leakage of intracellular substances; meanwhile, RONS also destroyed the intracellular anti-oxidative system, accelerated the oxidative stress and disrupted the intracellular redox homeostasis, subsequently the death of the cells. Moreover, the inactivation application in chicken breasts proved CAP could be a novel sanitizing process in practical industries.

Neuregulin 4 suppresses NASH-HCC development by restraining tumor-prone liver microenvironment.

The mammalian liver comprises heterogeneous cell types within its tissue microenvironment that undergo pathophysiological reprogramming in disease states, such as non-alcoholic steatohepatitis (NASH). Patients with NASH are at an increased risk for the development of hepatocellular carcinoma (HCC). However, the molecular and cellular nature of liver microenvironment remodeling that links NASH to liver carcinogenesis remains obscure. Here, we show that diet-induced NASH is characterized by the induction of tumor-associated macrophage (TAM)-like macrophages and exhaustion of cytotoxic CD8+ T cells in the liver. The adipocyte-derived endocrine factor Neuregulin 4 (NRG4) serves as a hormonal checkpoint that restrains this pathological reprogramming during NASH. NRG4 deficiency exacerbated the induction of tumor-prone liver immune microenvironment and NASH-related HCC, whereas transgenic NRG4 overexpression elicited protective effects in mice. In a therapeutic setting, recombinant NRG4-Fc fusion protein exhibited remarkable potency in suppressing HCC and prolonged survival in the treated mice. These findings pave the way for therapeutic intervention of liver cancer by targeting the NRG4 hormonal checkpoint.

Simultaneous illumination and imaging based on a single multimode fiber.

Due to the small core diameter, a single-core multimode fiber (MMF) has been extensively investigated for endoscopic imaging. However, an extra light path is always utilized for illumination in MMF imaging system, which takes more space and is inapplicable in practical endoscopy imaging. In order to make the imaging system more practical and compact, we proposed a dual-function MMF imaging system, which can simultaneously transmit the illumination light and the images through the same imaging fiber. Meanwhile, a new deep learning-based encoder-decoder network with full-connected (FC) layers was designed for image reconstruction. We conducted an experiment of transmitting images via a 1.6 m long MMF to verify the effectiveness of the dual-function MMF imaging system. The experimental results show that the proposed network achieves the best reconstruction performance compared with the other four networks on different datasets. Besides, it is worth mentioning that the cropped speckle patterns can still be used to reconstruct the original images, which helps to reduce the computing complexity significantly. We also demonstrated the ability of cross-domain generalization of the proposed network. The proposed system shows the potential for more compact endoscopic imaging without external illumination.

Effect of Emulsion Particle Size on the Encapsulation Behavior and Oxidative Stability of Spray Microencapsulated Sweet Orange Oil (Citrus aurantium var. dulcis).

Three different feed emulsions of different particle sizes were mixed with a modified starch and maltodextrin and spray dried to make a large (LP), small (SP), and nano-size encapsulated powder (NP), respectively. Emulsion size, oil content, loading capacity (LC), encapsulation efficiency (EE), water content, aw, scanning electron microscopy (SEM), glass transition temperature (Tg), as well as d-limonene release characteristic and limonene oxide formation rate during 37 °C and various aw storage were determined. With the increase of the feed emulsion size, the reconstituted emulsion size of the LP tended to increase and change to a bimodal distribution. The surface oil content increased with the increasing size of the reconstituted emulsion, and the opposite was true for EE. The smaller the reconstituted emulsion size, the higher Tg during a low aw condition. The Tg of the LP, SP and NP were 62, 88, and 100 °C, respectively, and NP > SP > LP. The release and the oxidative rate of d-limonene was the lowest for the NP and then increased for the SP and LP. The release and oxidative rates increased with the elevation of aw and peaked at 0.33. The powder surface morphological structure was intact, the spray-dried powder was more stable, and microstructure changed from a glass state to a rubbery state during storage.

Optimized Extraction and Characterization of Folates From Date Palm Fruits and Their Tracking During Fruits Wine Fermentation.

Folates belong to the essential B vitamins group and participate in one-carbon metabolism. Date palm fruits (Phoenix dactilyfera L. family Arecaceae) are consumed by millions of people and are good sources of folates. To date, no detailed study has been carried out on suitable methods for folate extraction from date palm fruits. In the present study, an experimental design using response surface methodology (RSM) was used to maximize the extraction yield of folates from date palm fruits by including enzymatic depectinization. By applying this new strategy and a UHPLC-MS/MS technique for analysis, total folate and different folate vitamers of three cultivars of date palm fruits (Muzafti, Zahdi, and Rubai), brewer's yeast, and fermented date wine were analyzed. The optimized extraction conditions of folates from date palm fruits were found to be a pectinase activity of 47.7 U, an incubation temperature of 40°C, and an incubation time of 38 min, which yielded a total folate content of 191-301 µg/100 g. In brewer's yeast, the extracted total folate content was very high (4,870 µg/100 g), and, in the resulting date wine, it reached a maximum of 700 µg/L on the fifth day. The predominant folate vitamers in date fruit and fruit wine were 5-formyltetrahydrofolate (5-CHO-THF) and 5-methyltetrahydrofolate (5-CH3-THF). During date palm fruit fermentation for up to 8 days, the 5-CHO-THF content gradually decreased by 20%, while 5-CH3-THF increased linearly from day 1 to day 5 (y = 0.058 x + 0.0284, R 2 = 0.9614). This study shows that date palm fruit and fruit wine are excellent sources of folate, and further study can be focused on different methods to improve folate stability during wine storage.

SLC22A14 is a mitochondrial riboflavin transporter required for sperm oxidative phosphorylation and male fertility.

Ablation of Slc22a14 causes male infertility in mice, but the underlying mechanisms remain unknown. Here, we show that SLC22A14 is a riboflavin transporter localized at the inner mitochondrial membrane of the spermatozoa mid-piece and show by genetic, biochemical, multi-omic, and nutritional evidence that riboflavin transport deficiency suppresses the oxidative phosphorylation and reprograms spermatozoa energy metabolism by disrupting flavoenzyme functions. Specifically, we find that fatty acid ß-oxidation (FAO) is defective with significantly reduced levels of acyl-carnitines and metabolites from the TCA cycle (the citric acid cycle) but accumulated triglycerides and free fatty acids in Slc22a14 knockout spermatozoa. We demonstrate that Slc22a14-mediated FAO is essential for spermatozoa energy generation and motility. Furthermore, sperm from wild-type mice treated with a riboflavin-deficient diet mimics those in Slc22a14 knockout mice, confirming that an altered riboflavin level causes spermatozoa morphological and bioenergetic defects. Beyond substantially advancing our understanding of spermatozoa energy metabolism, our study provides an attractive target for the development of male contraceptives.

Snapshot multispectral endomicroscopy.

Multispectral endomicroscopy provides tissue functional information in addition to structural information for accurate disease diagnosis. In this Letter, we propose a snapshot multispectral endomicroscope that employs a fiber bundle to deliver an in-body tissue spatial-spectral datastream to an external compressive spectral imager. Equipped with an end-to-end deep-learning-based reconstruction algorithm, we are able to capture tissue multispectral data in video rates and reconstruct high-resolution multispectral images with up to 24 spectral channels in near-real time.

Light-Driven Intramolecular C-N Cross-Coupling via a Long-Lived Photoactive Photoisomer Complex.

Reported herein is a visible-light-driven intramolecular C-N cross-coupling reaction under mild reaction conditions (metal- and photocatalyst-free, at room temperature) via a long-lived photoactive photoisomer complex. This strategy was used to rapidly prepare the N-substituted polycyclic quinazolinone derivatives with a broad substrate scope (>50 examples) and further exploited to synthesize the natural products tryptanthrin, rutaecarpine, and their analogues. The success of gram-scale synthesis and solar-driven transformation, as well as promising tumor-suppressing biological activity, proves the potential of this strategy for practical applications. Mechanistic investigations, including control experiments, DFT calculations, UV-vis spectroscopy, EPR, and X-ray single-crystal structure of the key intermediate, provides insight into the mechanism.

Organic cation transporter 3 (Oct3) is a distinct catecholamines clearance route in adipocytes mediating the beiging of white adipose tissue.

Beiging of white adipose tissue (WAT) is a particularly appealing target for therapeutics in the treatment of metabolic diseases through norepinephrine (NE)-mediated signaling pathways. Although previous studies report NE clearance mechanisms via SLC6A2 on sympathetic neurons or proinflammatory macrophages in adipose tissues (ATs), the low catecholamine clearance capacity of SLC6A2 may limit the cleaning efficiency. Here, we report that mouse organic cation transporter 3 (Oct3; Slc22a3) is highly expressed in WAT and displays the greatest uptake rate of NE as a selective non-neural route of NE clearance in white adipocytes, which differs from other known routes such as adjacent neurons or macrophages. We further show that adipocytes express high levels of NE degradation enzymes Maoa, Maob, and Comt, providing the molecular basis on NE clearance by adipocytes together with its reuptake transporter Oct3. Under NE administration, ablation of Oct3 induces higher body temperature, thermogenesis, and lipolysis compared with littermate controls. After prolonged cold challenge, inguinal WAT (ingWAT) in adipose-specific Oct3-deficient mice shows much stronger browning characteristics and significantly elevated expression of thermogenic and mitochondrial biogenesis genes than in littermate controls, and this response involves enhanced ß-adrenergic receptor (ß-AR)/protein kinase A (PKA)/cyclic adenosine monophosphate (cAMP)-responsive element binding protein (Creb) pathway activation. Glycolytic genes are reprogrammed to significantly higher levels to compensate for the loss of ATP production in adipose-specific Oct3 knockout (KO) mice, indicating the fundamental role of glucose metabolism during beiging. Inhibition of ß-AR largely abolishes the higher lipolytic and thermogenic activities in Oct3-deficient ingWAT, indicating the NE overload in the vicinity of adipocytes in Oct3 KO adipocytes. Of note, reduced functional alleles in human OCT3 are also identified to be associated with increased basal metabolic rate (BMR). Collectively, our results demonstrate that Oct3 governs ß-AR activity as a NE recycling transporter in white adipocytes, offering potential therapeutic applications for metabolic disorders.