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19 pages, 4784 KB  
Article
Uncoupling Protein 1 Promotes Nile Tilapia Resistance to Acute Cold Stress by Regulating Liver Metabolism
by Meiqing Li, Jirong Jia, Chenguang Liu, Ran Cai, Yang Yu, Xiaozheng Yu, Wei Feng, Caiyun Sun and Wensheng Li
Metabolites 2025, 15(10), 668; https://doi.org/10.3390/metabo15100668 (registering DOI) - 13 Oct 2025
Abstract
Background: Low temperature stress is a major environmental challenge affecting the growth, metabolism, and survival of many aquaculture species, including Nile tilapia (Oreochromis niloticus). Understanding the molecular mechanisms underlying cold tolerance is therefore essential for improving fish resilience and aquaculture [...] Read more.
Background: Low temperature stress is a major environmental challenge affecting the growth, metabolism, and survival of many aquaculture species, including Nile tilapia (Oreochromis niloticus). Understanding the molecular mechanisms underlying cold tolerance is therefore essential for improving fish resilience and aquaculture sustainability. Methods: In the present study, an acute cold stress model of Nile tilapia (Oreochromis niloticus) was established and it was found that uncoupling protein 1 (UCP1) was involved in the acute cold stress process of tilapia. Results: The upregulation of UCP1 in the liver under cold stimulation was regulated by stress hormones such as cortisol and adrenaline. UCP1 has a short half-life and is degraded by proteasomes. In tilapia primary hepatocytes, the addition of adrenergic receptor agonists resulted in mitochondrial membrane potential decreasing, while UCP1 siRNA transfection inhibited mitochondrial membrane potential. Biochemical characteristics indicate that UCP1 is a channel protein that mediates proton leakage. In addition, feeding and intraperitoneal injection of mitochondrial uncoupling agent BAM15 can alleviate the low-temperature stress of tilapia. Conclusions: UCP1 helps maintain the metabolic homeostasis of tilapia under acute cold stimulation and provides new insights into the mechanisms of cold resistance as well as potential treatment strategies in fish. Full article
(This article belongs to the Special Issue Nutrition, Metabolism and Physiology in Aquatic Animals)
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22 pages, 10124 KB  
Article
Cold Exposure Induces Swine Brown Adipocytes to Display an Island-like Distribution with Atypical Characteristics
by Zhenhua Guo, Lei Lv, Hong Ma, Liang Wang, Bo Fu, Fang Wang, Shuo Yang, Di Liu and Dongjie Zhang
Int. J. Mol. Sci. 2025, 26(20), 9871; https://doi.org/10.3390/ijms26209871 (registering DOI) - 10 Oct 2025
Viewed by 93
Abstract
The original purpose of this study was to compare human and pig scRNA-seq data to determine why pigs do not have brown adipocytes. However, during the experiment, we identified brown adipocytes in pigs. Therefore, we aimed to confirm that these adipocytes were brown [...] Read more.
The original purpose of this study was to compare human and pig scRNA-seq data to determine why pigs do not have brown adipocytes. However, during the experiment, we identified brown adipocytes in pigs. Therefore, we aimed to confirm that these adipocytes were brown adipocytes via a comparative analysis using typical mouse brown adipose tissue sections. We found that swine brown adipocytes were distributed in an island-like pattern, with three typical characteristics: (1) numerous mitochondria and small lipid droplets, (2) a cellular volume smaller than that of white adipocytes, and (3) expression of specific marker genes (EBF2 and ATP2B4). The expression levels of the thermogenesis-related genes UCP2/3 were not significantly increased. Thus, we conducted ceRNA network analysis, revealing that high expression of the key microRNA miR-10383 increased the thermogenic efficiency of UCP3 in the cold exposure group. In addition, the epigenetic memory of UCP3 was disrupted. Chromatin accessibility and Whole-Transcriptome Sequencing of Groin Adiposesibility results revealed peaks in the promoter regions of the UCP2/3 genes. In our discussion of the study’s limitations, we explain how to repeat the experiment to significantly increase the UCP2/3 protein content. This study fills a research gap regarding brown fat in pigs and can provide a reference for future studies on fat metabolism. Full article
(This article belongs to the Section Molecular Biology)
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11 pages, 270 KB  
Article
Impact of Two Surgical Techniques for Umbilical Hernia Repair, With and Without Peritoneal Opening, on Pain Response, Sedation, and Oxidative Stress in Calves
by Claudia Interlandi, Filippo Spadola, Fabio Bruno, Giuseppe Bruschetta, Francesco Macrì, Andrea Spadaro, Giovanni Barone and Giovanna Lucrezia Costa
Vet. Sci. 2025, 12(10), 963; https://doi.org/10.3390/vetsci12100963 - 9 Oct 2025
Viewed by 194
Abstract
This study aimed to compare effects on homeostasis and postoperative outcomes of two surgical techniques for umbilical hernia repair in calves. Fifty-two calves were enrolled and randomly assigned to two groups: Group A (open technique) and Group C (closed technique). This was a [...] Read more.
This study aimed to compare effects on homeostasis and postoperative outcomes of two surgical techniques for umbilical hernia repair in calves. Fifty-two calves were enrolled and randomly assigned to two groups: Group A (open technique) and Group C (closed technique). This was a prospective controlled clinical trial. Sedation was induced with romifidine, and butorphanol. Cardiopulmonary parameters, sedation scores, and body temperature were recorded at multiple perioperative timepoints (T0–T8). Postoperative pain was assessed using the UNESP-Botucatu UCPS-IV scale. Oxidative stress was evaluated by measuring serum malondialdehyde (MDA) and plasma serotonin (5-HT) concentrations at T0 and 36 h postoperatively T9. Physiological parameters remained within normal limits in both groups. Postoperative pain scores were significantly lower in Group C than in Group A (p < 0.001), with later onset of rescue analgesia 40 vs. 30 min post-standing, respectively, p < 0.001. MDA levels increased postoperatively in both groups, with a greater rise in Group A (p < 0.001), 5-HT decreased in Group A and increased in Group C (p = 0.020). The closed surgical technique for umbilical hernia repair, avoiding peritoneal opening, was associated with reduced postoperative pain and oxidative stress, suggesting it is a less invasive than the open surgical technique. Full article
17 pages, 987 KB  
Article
Bioemulsifier Produced by Aspergillus niger UCP 1064 Isolated from Caatinga Soil as a Promising Molecule for Scaled-Up Pharmaceutical Applications
by Uiara Maria de Barros Lira Lins, Rosileide Fontenele da Silva Andrade and Galba Maria de Campos-Takaki
Fermentation 2025, 11(10), 562; https://doi.org/10.3390/fermentation11100562 - 29 Sep 2025
Viewed by 475
Abstract
This study presents the production, characterization, and potential pharmaceutical application of a bioemulsifier synthesized by Aspergillus niger UCP 1064 by submerged fermentation using agro-industrial residues (cassava wastewater and soluble starch). The compound exhibited a high emulsification index (EI24 > 88%) against hydrophobic [...] Read more.
This study presents the production, characterization, and potential pharmaceutical application of a bioemulsifier synthesized by Aspergillus niger UCP 1064 by submerged fermentation using agro-industrial residues (cassava wastewater and soluble starch). The compound exhibited a high emulsification index (EI24 > 88%) against hydrophobic substrates, effectively reduced surface tension, and remained stable across a wide range of pH (2–12), temperatures (5–100 °C), and salinity levels (0–20% NaCl). Microscopic analysis confirmed the formation of stable oil-in-water (O/W) emulsions, while biochemical tests identified the compound as a glycolipoprotein. Rheological assays demonstrated a significant reduction in oil viscosity, enhancing fluidity. Through factorial design and response surface methodology, production conditions were optimized, achieving yields of up to 3.18 g/L. A theoretical scale-up indicated technical feasibility for pharmaceutical applications; however, challenges such as process reproducibility, sterility, and regulatory compliance persist. These findings highlight the bioemulsifier’s potential as a sustainable and biocompatible alternative for drug delivery systems. Full article
(This article belongs to the Special Issue Scale-Up Challenges in Microbial Fermentation)
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34 pages, 4897 KB  
Article
Long-Term Effects of Stress During Adolescence on the Sex-Dependent Responses of Thyroid Axis and Target Tissues to Exercise in Male and Female Wistar Rats
by Marco Parra-Montes de Oca, Lorraine Jaimes-Hoy, Karen Garduño, Rodrigo García-Herrera, Jean-Louis Charli and Patricia Joseph-Bravo
Int. J. Mol. Sci. 2025, 26(19), 9425; https://doi.org/10.3390/ijms26199425 - 26 Sep 2025
Viewed by 263
Abstract
The response of the hypothalamic–pituitary–thyroid (HPT) axis to energy demands is perturbed by previous chronic stress perceived during the neonatal or adult periods. We examined the effects of chronic variable stress (CVS) during adolescence on the responses of the HPT axis and target [...] Read more.
The response of the hypothalamic–pituitary–thyroid (HPT) axis to energy demands is perturbed by previous chronic stress perceived during the neonatal or adult periods. We examined the effects of chronic variable stress (CVS) during adolescence on the responses of the HPT axis and target tissues of adult rats to 14 days of voluntary wheel running (Ex) or pair-feeding (PF) to match the reduced food intake of exercised rats. CVS increased the expression of Gr in the paraventricular nucleus (PVN) and of Npy in the mediobasal hypothalamus (MBH) in males; serum corticosterone concentration increased (1.5×), MBH Dio2 and PVN Trh decreased (40%) in both sexes, serum fT4 increased only in males, while T3 and fT3 increased (2×) in females. Exercise decreased Cort and increased PVN Trh expression only in males. In both sexes, it increased MBH Pomc and Dio2 (2×), skeletal muscle Dio2 and Pgc1a (2×), inguinal and perigonadal white adipose tissue (WAT) Adrb3, Dio2, Pparg, Hsl (1.5×), and brown adipose tissue Adrb3, Dio2, and Ucp1. All exercise-induced changes were repressed in CVS-Ex, except Hsl in inguinal WAT of both sexes, or BAT Dio2 in females, which, in contrast, was stimulated (1.5×). PF had lower values than sedentary in most parameters. These results support the idea that adolescent stress affects adult metabolic and neuroendocrine responses to exercise in a sex-specific manner. Full article
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13 pages, 675 KB  
Article
Nano-Encapsulated Berberine Is a Potential Therapeutic Agent for Adipose Tissue Browning in C57BL/6J Mice
by Aslıhan Alpaslan, Kübra Uçar Baş, Elif Didem Örs Demet, Dilem Tuğal Aslan, Tuba Reçber, Süleyman Can Öztürk, Tugba Gulsun, Mustafa Çelebier and Zeynep Göktaş
Medicina 2025, 61(10), 1738; https://doi.org/10.3390/medicina61101738 - 24 Sep 2025
Viewed by 314
Abstract
Background and Objectives: Berberine is a promising phytochemical for obesity prevention due to its effects on adipogenesis and adipose tissue browning. Despite the benefits shown in cell studies, the clinical use of berberine is limited because of its low stability and bioavailability. Materials [...] Read more.
Background and Objectives: Berberine is a promising phytochemical for obesity prevention due to its effects on adipogenesis and adipose tissue browning. Despite the benefits shown in cell studies, the clinical use of berberine is limited because of its low stability and bioavailability. Materials and Methods: Our study aimed to investigate the effects of intravenous liposomal and free berberine on body weight and adipose tissue browning in C57BL/6J mice. The mice were divided into two main groups for obesity prevention and treatment: the prevention group received treatment with a high-fat diet for 10 weeks; the recovery group received treatment after 10 weeks on a high-fat diet. Treatments included liposomal berberine (10 mcM), free berberine (10 mcM), and void nano-encapsule, and PBS was used as a control. Results: Berberine did not affect body weight in the prevention group. In the treatment group, nano-berberine reduced weight gain, while free berberine caused weight loss (p < 0.05). PRDM16 and CIDEA expressions in white and brown adipose tissues were higher in the berberine-treated groups (p < 0.05). No changes were observed in UCP1, PGC1α, C/EBPβ, and FABP4 expressions. The protein concentrations of UCP1, PGC1α, and PPARγ did not change. Conclusions: The effects of liposomal berberine on gene expression and protein concentrations were not different from the free form, but the nano form had higher stability. Full article
(This article belongs to the Section Pharmacology)
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26 pages, 2412 KB  
Review
Functional Complexity of Thermogenic Adipose Tissue: From Thermogenesis to Metabolic and Fibroinflammatory Crosstalk
by Wael Jalloul, Irena Cristina Grierosu, Despina Jalloul, Cipriana Stefanescu and Vlad Ghizdovat
Int. J. Mol. Sci. 2025, 26(18), 9045; https://doi.org/10.3390/ijms26189045 - 17 Sep 2025
Viewed by 785
Abstract
Brown adipose tissue (BAT) has shifted from being considered a transient thermogenic organ of infancy to a metabolically dynamic and multifunctional tissue throughout life. Histologically and developmentally distinct from white and beige adipocytes, BAT originates from a myogenic lineage and is characterised by [...] Read more.
Brown adipose tissue (BAT) has shifted from being considered a transient thermogenic organ of infancy to a metabolically dynamic and multifunctional tissue throughout life. Histologically and developmentally distinct from white and beige adipocytes, BAT originates from a myogenic lineage and is characterised by a high mitochondrial density, multilocular lipid droplets, and abundant sympathetic innervation. Its defining function, non-shivering thermogenesis, is mediated by uncoupling protein 1 (UCP1) and complemented by alternative mechanisms such as futile creatine and calcium cycling. Beyond heat production, thermogenic fat is crucial in regulating whole-body metabolism. It contributes to glucose, lipid, and branched-chain amino acid homeostasis, and engages in endocrine and paracrine signalling through a rich secretome of batokines, lipid mediators, and extracellular vesicle-bound microRNAs. These signals orchestrate crosstalk with the liver, skeletal muscle, pancreas, and immune system, enhancing insulin sensitivity, vascularisation, and anti-inflammatory responses. Brown/Beige fat also exhibits notable anti-fibrotic properties and supports adipose tissue remodelling, maintaining structural and functional plasticity under metabolic stress. This review offers a comprehensive synthesis of thermogenic adipose tissue biology, integrating its structural, developmental, and molecular features with its expanding physiological functions, highlighting its pivotal role in energy balance as well as its emerging therapeutic potential in obesity, type 2 diabetes, and related metabolic disorders. Full article
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13 pages, 3040 KB  
Article
The Utility of Umbilical Cord Pulse Oximetry—A Translational Study with Four Minutes of Deferred Cord Clamping Using an Asphyxiated Preterm Ovine Model
by Justin Helman, Mausma Bawa, Sylvia Gugino, Nicole Bradley, Lori Nielsen, Arun Prasath, Clariss Blanco, Mary Divya Kasu, Hamza Abbasi, Munmun Rawat and Praveen Chandrasekharan
Children 2025, 12(9), 1205; https://doi.org/10.3390/children12091205 - 10 Sep 2025
Viewed by 523
Abstract
Background: Expert guidelines recommend using pulse oximetry (PO) in the delivery room to monitor oxygen saturation (SpO2) and heart rate (HR). Umbilical cord pulse oximetry (UCP) is a novel concept that, despite being postductal, could provide accurate measurements of SpO2 [...] Read more.
Background: Expert guidelines recommend using pulse oximetry (PO) in the delivery room to monitor oxygen saturation (SpO2) and heart rate (HR). Umbilical cord pulse oximetry (UCP) is a novel concept that, despite being postductal, could provide accurate measurements of SpO2 and HR, as it overcomes barriers associated with skin pigmentation. Methods: This pilot study used NONIN pulse oximetry on an intact umbilical cord that underwent deferred cord clamping (DCC) to evaluate umbilical cord SpO2 in a preterm asphyxiated ovine model (N of 5) with an HR of <100 bpm. The UCP HR served as a surrogate marker for umbilical vessel flow. A receiver operator characteristic (ROC) curve was used to evaluate UCP parameters with arterial saturations (SaO2) and carotid HR between 2 and 10 min. Results: Following asphyxia, five preterm lambs underwent DCC for 4 min. A significant relationship was noted between SaO2 and umbilical SpO2 (area under the curve (AUC) of 0.907, CI 0.857–0.968, p < 0.0001) along with carotid and umbilical HR (AUC) of 0.842 (CI 0.663–0.902, p < 0.0001). Conclusions: In a translational preterm model, UCP accurately predicted preductal SaO2 and carotid HR (a surrogate for umbilical flow). Using UCP in the delivery room will help guide supplemental oxygen and determine the optimal duration of clamping the umbilical cord. These proof-of-concept studies/pilot findings require validation with larger animal cohorts and newborn infants. Full article
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18 pages, 2631 KB  
Article
Mitochondrial ATP Biosynthesis Is Negatively Associated with FFA in Cardiac and Skeletal Muscle During the Development of Obesity in a Rodent Model
by Vianey Nava-Aguilar, Angelica Ruiz-Ramirez, Zeltzin Alejandra Ceja-Galicia, Maria de la Luz Hernandez Esquivel, Magalena Cristobal Garcia, Roxana Carbó Zabala, Guillermo-Celestino Cardoso-Saldaña and Mohammed El-Hafidi
Int. J. Mol. Sci. 2025, 26(18), 8768; https://doi.org/10.3390/ijms26188768 - 9 Sep 2025
Viewed by 540
Abstract
Many factors related to obesity can impact how mitochondria produce ATP, such as the uncoupling of oxidative phosphorylation (OXPHOS) caused by proton leaks from built-up free fatty acids (FFA), the increased levels of uncoupling proteins (UCPs), and changes in the levels of ATPase [...] Read more.
Many factors related to obesity can impact how mitochondria produce ATP, such as the uncoupling of oxidative phosphorylation (OXPHOS) caused by proton leaks from built-up free fatty acids (FFA), the increased levels of uncoupling proteins (UCPs), and changes in the levels of ATPase inhibitory protein factors 1 (IF1). Therefore, the present study aimed to assess the rate of ATP synthesis in mitochondria isolated from skeletal and cardiac muscle from animal models of sucrose diet-induced obesity at different time periods. Short periods of sucrose intake (6 and 12 weeks) are sufficient to induce fat accumulation, hypertriglyceridemia, and high plasma FFA. However, a significant decline in the ATP synthesis rate starts to be obvious in mitochondria from skeletal muscle after 24 weeks of sucrose consumption. This impairment of ATP synthesis is associated with increased FFA in skeletal muscle homogenate. ATP synthesis rates in both skeletal and cardiac muscle were found to be sensitive to oleic acid and GDP, a physiological inhibitor of UCPs that has been shown to increase with aging. In addition, a sucrose diet increases the IF1 content in both skeletal and heart muscle, probably to avoid the hydrolytic activity of ATP synthase. In mitochondria from heart muscle, a decrease in the ATP synthesis rate was only observed according to the age in both groups of rats, and it was not affected by sucrose feeding. Our results suggest that the decline of the ATP synthesis rate in mitochondria from skeletal muscle can be due to the accumulation of FFA in skeletal muscle tissue as uncouplers, and the IF1 overexpression induced by the sucrose diet is a response mechanism to avoid the ATP hydrolysis and to save the energy charge reduced by FFA-uncoupling OXPHOS. Full article
(This article belongs to the Special Issue Mitochondrial Function in Health and Disease, 3rd Edition)
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28 pages, 2083 KB  
Review
The Dual Role of Perivascular Adipose Tissue in Vascular Homeostasis and Atherogenesis: From Physiology to Pathological Implications
by Raluca Niculescu, Adina Stoian, Emil Marian Arbănași, Eliza Russu, Dragoș-Florin Babă, Andrei Manea, Mircea Stoian, Florina Ioana Gliga, Iuliu Gabriel Cocuz, Adrian Horațiu Sabău, Dan-Alexandru Szabo and Ovidiu Simion Cotoi
Int. J. Mol. Sci. 2025, 26(17), 8320; https://doi.org/10.3390/ijms26178320 - 27 Aug 2025
Viewed by 1417
Abstract
Atherosclerosis is now recognized as a chronic inflammatory disease of the arterial wall, in which perivascular adipose tissue (PVAT) has evolved from a passive structural component to a key player in regulating vascular homeostasis and the pathophysiology of atherosclerosis, playing an active, not [...] Read more.
Atherosclerosis is now recognized as a chronic inflammatory disease of the arterial wall, in which perivascular adipose tissue (PVAT) has evolved from a passive structural component to a key player in regulating vascular homeostasis and the pathophysiology of atherosclerosis, playing an active, not just structural, role. PVAT surrounds blood vessels and influences them metabolically, immunologically, and vascularly by secreting adipokines, cytokines, and other bioactive mediators. Under physiological conditions, PVAT has protective roles, as it produces adiponectin, nitric oxide (NO), and other vasodilatory factors that help maintain vascular tone and reduce inflammation. In particular, brown-like PVAT (rich in Uncoupling Protein-1 (UCP1) and mitochondria) offers significant vasoprotective effects. Under pathological conditions (obesity, dyslipidemia, insulin resistance), PVAT undergoes a phenotypic transition towards a pro-inflammatory profile by increasing leptin, tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) secretion and decreasing adiponectin, contributing to endothelial dysfunction, vascular smooth muscle cell (VSMC) proliferation, local immune cell recruitment, extracellular matrix (ECM) remodeling, and fibrosis. PVAT plays a complex role in vascular health and disease, interacting with systemic metabolism through the secretion of bioactive molecules. Metabolic imbalances can promote PVAT inflammation. Epigenetic alterations and micro ribonucleic acid (miRNAs) can influence PVAT inflammation, and modern imaging methods for PVAT assessment, such as the fat attenuation index (FAI) and artificial intelligence-assisted radiomic profiling, may become predictive biomarkers of cardiac risk. Future directions aim to identify biomarkers and develop targeted therapies that modulate PVAT inflammation and dysfunction in the context of cardiovascular diseases. Full article
(This article belongs to the Special Issue Molecular Research in Cardiovascular Disease, 3rd Edition)
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14 pages, 2235 KB  
Article
Comparison of Anti-Obesity Effects of Ginger Extract Alone and Mixed with Long Pepper Extract
by Gunju Song, Hyein Han, Heegu Jin, Jongwon Kim, Hyeongmin Kim, Yi-Seul Seo, Heewon Song and Boo-Yong Lee
Biomedicines 2025, 13(9), 2077; https://doi.org/10.3390/biomedicines13092077 - 26 Aug 2025
Viewed by 1027
Abstract
Background/Objectives: Obesity is a chronic metabolic disorder characterized by the excessive expansion of adipose tissue and impaired energy homeostasis. Natural products, such as plant extracts, are gaining attention as potential anti-obesity agents. This study aimed to evaluate and compare the anti-obesity effects of [...] Read more.
Background/Objectives: Obesity is a chronic metabolic disorder characterized by the excessive expansion of adipose tissue and impaired energy homeostasis. Natural products, such as plant extracts, are gaining attention as potential anti-obesity agents. This study aimed to evaluate and compare the anti-obesity effects of ginger (Zingiber officinale Roscoe) extract alone and as a mixture with long pepper (Piper longum L.) extract in a mouse model of high-fat diet-induced obesity. Methods: Male ICR mice were fed a high-fat diet to induce obesity and were orally administered ginger extract (60 mg/kg/day) or a 1:1 mixture of ginger and long pepper extracts (30 mg/kg/day each) for 8 weeks. Body weight, fat mass, glucose tolerance, and serum lipid levels were measured. Results: Ginger extract alone significantly reduced body weight gain and visceral and subcutaneous fat accumulation and improved glucose homeostasis and serum lipid profiles compared to the high-fat diet group. These effects were more pronounced than those observed with the mixture group. Ginger extract upregulated lipolytic markers via activation of the protein kinase A (PKA) signaling pathway and increased expression of uncoupling protein 1 (UCP1), indicating browning of white adipose tissue. Conclusions: Ginger extract alone exhibited significant anti-obesity effects compared to the mixture with long pepper extract. These findings suggest that ginger extract may serve as a promising natural agent for the prevention and management of obesity-related metabolic dysfunction. Full article
(This article belongs to the Special Issue Advanced Research in Metabolic Syndrome (2nd Edition))
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16 pages, 3190 KB  
Article
Lipin-1 Drives Browning of White Adipocytes via Promotion of Brown Phenotype Markers
by Siti Sarah Hamzah, Liyana Ahmad Zamri, Siti Azrinnah Abdul Azar, Siti Mastura Abdul Aziz, Shazana Rifham Abdullah and Norhashimah Abu Seman
Biomedicines 2025, 13(9), 2069; https://doi.org/10.3390/biomedicines13092069 - 25 Aug 2025
Viewed by 676
Abstract
Background: Enhancing adipose tissue functionality is a promising cellular-level approach to combating obesity. White adipose tissue (WAT) can acquire beige or brown adipose tissue (BAT)-like properties, characterized by increased thermogenesis and energy dissipation. While the SIRT1-SRSF10–Lipin-1 axis has been identified in hepatocytes, where [...] Read more.
Background: Enhancing adipose tissue functionality is a promising cellular-level approach to combating obesity. White adipose tissue (WAT) can acquire beige or brown adipose tissue (BAT)-like properties, characterized by increased thermogenesis and energy dissipation. While the SIRT1-SRSF10–Lipin-1 axis has been identified in hepatocytes, where Lipin-1 regulates triglyceride metabolism, its role in adipocytes remains unclear. This study aimed to investigate the function of Lipin-1 in 3T3-L1 preadipocytes and its interaction with SIRT1, SRSF10, and PPARγ in promoting browning-like transcriptional responses. Methods: Mouse 3T3-L1 preadipocytes were treated during differentiation with either rosiglitazone (RGZ), the SIRT1 activator SRT1720, or the SIRT1 inhibitor EX527. Gene expression was assessed by real-time PCR, and protein levels were measured using the Simple Western blot system. Data were compared with untreated controls and analyzed using GraphPad Prism. Results: Lipin-1 expression was significantly upregulated by RGZ treatment, alongside increased transcription of Sirt1 and Srsf10, supporting the presence of this regulatory axis in adipocytes. Elevated Srsf10 favored the production of the Lipin-1b isoform, whereas SIRT1 inhibition reversed these effects, confirming its upstream role. Pathway activation further enhanced the expression of browning markers, including Ucp1, Pgc1a, PRDM16, and CIDEA. Conclusions: These findings demonstrate that Lipin-1 interacts with the SIRT1–PPARγ–SRSF10 axis in adipocytes and contributes to the acquisition of beige/brown-like characteristics in WAT. This regulatory pathway may represent a potential target for improving lipid metabolism and metabolic health. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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21 pages, 5020 KB  
Article
Divergent Hepatic and Adipose Tissue Effects of Kupffer Cell Depletion in a Male Rat Model of Metabolic-Associated Steatohepatitis
by Morena Wiszniewski, Diego Mori, Silvia I. Sanchez Puch, Camila Martinez Calejman, Cora B. Cymeryng and Esteban M. Repetto
Biology 2025, 14(8), 1058; https://doi.org/10.3390/biology14081058 - 15 Aug 2025
Cited by 1 | Viewed by 854
Abstract
Kupffer cells (KCs) play a pivotal role in the progression of metabolic-associated steatohepatitis (MASH). This study evaluated the impact of short-term KC depletion induced by gadolinium chloride (GdCl3) in a rat model of MASH. The intervention with GdCl3 effectively reduced [...] Read more.
Kupffer cells (KCs) play a pivotal role in the progression of metabolic-associated steatohepatitis (MASH). This study evaluated the impact of short-term KC depletion induced by gadolinium chloride (GdCl3) in a rat model of MASH. The intervention with GdCl3 effectively reduced KC markers CD68 and Clec4f, together with pro-inflammatory cytokines (IL-1β, TNFα, NOS2), without affecting anti-inflammatory markers (IL-10, MRC1). Histologically, GdCl3 reduced hepatocyte ballooning and NAS despite persistent steatosis. KC depletion was associated with decreased oxidative stress markers (TBARS, 3-nitrotyrosine) and antioxidant enzyme activity (SOD, catalase). Additionally, markers of endoplasmic reticulum stress (ATF4, GRP78, CHOP, P58IPK) and apoptosis (BAX/BCL2 ratio, cleaved caspase-3) were diminished. Despite these improvements, GdCl3 had no effect on lipid or glucose metabolism in the liver, associated with persistent elevation of PTP1B expression induced by SRD intake. KC depletion, however, increased FGF21 expression. GdCl3 treatment improved systemic insulin sensitivity and reduced fasting glucose and NEFA serum levels. In white adipose tissue, the treatment decreased adipocyte size, restored insulin signaling, and inhibited lipolysis (ATGL expression) without altering macrophage infiltration (IBA) or thermogenic protein levels (UCP1) in SRD rats. These findings suggest that KC depletion modulates liver-to-adipose tissue crosstalk, potentially through FGF21 signaling, contributing to improved systemic metabolic homeostasis of SRD animals. Full article
(This article belongs to the Special Issue Cellular and Molecular Biology of Liver Diseases)
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16 pages, 4236 KB  
Article
Toxic Effects of Tetramethyl Bisphenol A on Embryonic–Larval Development of Zebrafish (Danio rerio)
by Ermei Yin, Manwen Zeng, Haipeng Yan, Jiahao Gao, Zuchun Chen, Ning Zhang, Yusong Guo, Zhongduo Wang and Zhongdian Dong
Fishes 2025, 10(8), 407; https://doi.org/10.3390/fishes10080407 - 14 Aug 2025
Viewed by 555
Abstract
Tetramethyl bisphenol A (TMBPA), a novel alternative to Bisphenol A, is widely used as an industrial flame retardant and a raw material for tetramethyl polycarbonate plastics. With the increasing use of TMBPA, its aquatic ecological risks remain unclear. Therefore, this study investigated the [...] Read more.
Tetramethyl bisphenol A (TMBPA), a novel alternative to Bisphenol A, is widely used as an industrial flame retardant and a raw material for tetramethyl polycarbonate plastics. With the increasing use of TMBPA, its aquatic ecological risks remain unclear. Therefore, this study investigated the developmental toxicity of TMBPA using zebrafish (Danio rerio) as a model, exposing embryos to 0.5, 5, 50, and 200 μg/L TMBPA for 120 h. The results showed that treatment with 5, 50, and 200 μg/L TMBPA decreased the hatching rate of zebrafish embryos at 48 h post-fertilization (hpf), while no significant difference was observed at 72 hpf. Meanwhile, TMBPA exposure at all concentrations showed no significant effect on the survival rate. Furthermore, a high concentration of TMBPA (200 μg/L) significantly reduced the total length and suppressed swimming ability in zebrafish larvae. In addition, gene expression analysis revealed impacts on antioxidant system (cat, gpx, mn-sod, keap1, ucp2, nrf2), hypothalamic–pituitary–thyroid (HPT) axis (ttr, ugt1ab, trβ), cardiac developmental (tbx2b, myl7, bmp4, notch1b, amhc), and the hypothalamic–pituitary–adrenal (HPA) axis (pomca and nr3c1). The results indicated that TMBPA exposure adversely disrupted embryo hatching and larval development of zebrafish, accompanied by altering the expression of functional genes in larvae. These results provide further evidence for the potential environmental hazard posed by TMBPA. Full article
(This article belongs to the Section Environment and Climate Change)
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23 pages, 8052 KB  
Article
The Capability to Undergo ACSL4-Mediated Ferroptosis Is Acquired During Brown-like Adipogenesis and Affected by Hypoxia
by Markus Mandl, Elisabeth Heuboeck, Peter Benedikt, Florian Huber, Olga Mamunchak, Sonja Grossmann, Michaela Kotnik, Esma Hamzic-Jahic, Charnkamal Singh Bhogal, Anna-Maria Lipp, Edeltraud Raml, Werner Zwerschke, Martin Wabitsch, Jakob Voelkl, Andreas Zierer and David Bernhard
Cells 2025, 14(16), 1247; https://doi.org/10.3390/cells14161247 - 13 Aug 2025
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Abstract
Adipose tissue enlargement in obesity leads to hypoxia, which may promote premature aging. This study aimed to understand the hypoxic response in 3D cultures of SGBS cells, a model for brown-like adipose tissue expressing uncoupling protein 1 (UCP1). Single-nucleus RNA sequencing of SGBS [...] Read more.
Adipose tissue enlargement in obesity leads to hypoxia, which may promote premature aging. This study aimed to understand the hypoxic response in 3D cultures of SGBS cells, a model for brown-like adipose tissue expressing uncoupling protein 1 (UCP1). Single-nucleus RNA sequencing of SGBS organoids revealed a heterogeneous composition and sub-population-specific responses to hypoxia. The analysis identified a cluster of transcriptional repression, indicating dying cells, and implied a role of ferroptosis in this model. Further experiments with SGBS cells and white adipose tissue-derived stem/progenitor cells showed that Acyl-CoA synthetase long-chain family member 4 (ACSL4), a key enzyme in ferroptosis, is expressed only in the presence of browning factors. Hypoxia downregulated ACSL4 protein in SGBS organoids but induced an inflammaging phenotype. Analysis of brown-like epicardial adipose tissue from cardiac surgery patients revealed a significant positive correlation of ACSL4 mRNA with UCP1 and hypoxia-inducible pro-inflammatory markers, while ACSL4 protein appeared to be inversely correlated. In conclusion, this study demonstrates that adipocytes’ capability to undergo ACSL4-mediated ferroptosis is linked to brown-like adipogenesis, suggesting an opportunity to modulate ferroptotic signaling in adipose tissue. The dual role of hypoxia by inhibiting ACSL4 but promoting inflammaging indicates a relationship between ferroptosis and aging that warrants further investigation. Full article
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