Browning Of White Adipocytes Research Articles

Rosiglitazone-induced white adipocyte browning is regulated by actin and Myh9

AimsThis study investigates the role of actin polymerization and Myh9 in mediating lipid droplet (LD) fission during rosiglitazone-induced browning of white adipocytes. The aim is to understand how LD splitting might contribute to the beige conversion of white adipose tissue, providing insights into adipocyte plasticity and metabolic regulation. Materials and methodsC3H10 T1/2-differentiated adipocytes were used as a classical model to study white adipocyte browning. Rosiglitazone was applied to induce browning, and the interactions between LDs and actin, as well as the distribution of Myh9, were assessed using immunofluorescence and Western blotting. In vivo, we employed a microfilament inhibitor to block actin polymerization in cold-stimulated mice and evaluated changes in LD morphology and browning. Furthermore, dynamic live-cell imaging using confocal microscopy was conducted to observe the real-time behavior of LDs during the browning process and to determine whether they undergo fission. Main findingsOur results demonstrate that rosiglitazone significantly induces LD size reduction, a process correlated with the increased contact of LDs with microfilaments. Inhibition of actin polymerization prevented both the reduction in LD size and the browning of white adipocytes, indicating that actin plays a critical role. Myh9 was enriched at the LD fission sites, forming a structure resembling a contractile ring. Overexpression of Myh9 promoted the shrinkage of LD, suggesting that it may be involved in LD fission. SignificanceThis study identifies actin and Myh9 as key regulators of LD fission in rosiglitazone-induced browning of white adipocytes, offering new insights into the cellular mechanisms of adipocyte plasticity. The findings propose a novel pathway by which LD dynamics contribute to the beige conversion of white fat, with potential implications for metabolic disease therapies targeting adipocyte function and energy expenditure.

Mitochondrial Function and Dysfunction in White Adipocytes and Therapeutic Implications.

For a long time, white adipocytes were thought to function as lipid storages due to the sizeable unilocular lipid droplet that occupies most of their space. However, recent discoveries have highlighted the critical role of white adipocytes in maintaining energy homeostasis and contributing to obesity and related metabolic diseases. These physiological and pathological functions depend heavily on the mitochondria that reside in white adipocytes. This article aims to provide an up-to-date overview of the recent research on the function and dysfunction of white adipocyte mitochondria. After briefly summarizing the fundamental aspects of mitochondrial biology, the article describes the protective role of functional mitochondria in white adipocyte and white adipose tissue health and various roles of dysfunctional mitochondria in unhealthy white adipocytes and obesity. Finally, the article emphasizes the importance of enhancing mitochondrial quantity and quality as a therapeutic avenue to correct mitochondrial dysfunction, promote white adipocyte browning, and ultimately improve obesity and its associated metabolic diseases. © 2024 American Physiological Society. Compr Physiol 14:5581-5640, 2024.

Role of cannabinoid type 2 receptor in white adipocyte browning

Role of cannabinoid type 2 receptor in white adipocyte browning

Combinatorial effect of Apigenin-resveratrol on white adipocyte plasticity and trans-differentiation for activating lipid metabolism.

Inducing browning in white adipocytes has emerged as a promising therapeutic approach for addressing obesity. Bioactive that modulate the WAT microenvironment to induce trans browning in white adipocytes have been explored as a strategy to control unregulated lipid storage. However, relying on a single bioactive for modulating lipid metabolism has proven insufficient in obese individuals during human trials, because these compounds primarily activate a single biochemical pathway in promoting browning. Consequently, there is a growing emphasis on targeting multiple pathways to ensure a safe and effective browning process. The present study investigated the combinatorial effect of bioactives namely Apigenin and Resveratrol for activating multiple pathways for effective trans-browning of white adipocytes. The combination was seen to promote the browning more effectively than the single bioactive, as the combination simultaneously activated multiple signaling pathways to induce angiogenesis-mediated browning in primary white adipocytes isolated from obese mice. Activation of PI3K signaling via estrogen receptor-α-dependent pathway resulted in simultaneous activation of angiogenesis and trans browning in white adipocytes. The study provides valuable insights into the potential use of bioactives in combination with therapeutic intervention to improve the overall health of obese subjects by enhancing lipid metabolism by activating trans-differentiation of white adipocytes.

Extracellular vesicles in tumor-adipose tissue crosstalk: key drivers and therapeutic targets in cancer cachexia

Cancer cachexia is a complex metabolic syndrome characterized by unintentional loss of skeletal muscle and body fat. This syndrome is frequently associated with different types of cancer and negatively affects the prognosis and outcome of these patients. It involves a dynamic interplay between tumor cells and adipose tissue, where tumor-derived extracellular vesicles (EVs) play a crucial role in mediating intercellular communication. Tumor cells release EVs containing bioactive molecules such as hormones (adrenomedullin, PTHrP), pro-inflammatory cytokines (IL-6), and miRNAs (miR-1304-3p, miR-204-5p, miR-155, miR-425-3p, miR-146b-5p, miR-92a-3p), which can trigger lipolysis and induce the browning of white adipocytes contributing to a cancer cachexia phenotype. On the other hand, adipocyte-derived EVs can reprogram the metabolism of tumor cells by transporting fatty acids and enzymes involved in fatty acid oxidation, resulting in tumor growth and progression. These vesicles also carry leptin and key miRNAs (miR-155-5p, miR-10a-3p, miR-30a-3p, miR-32a/b, miR-21), thereby supporting tumor cell proliferation, metastasis formation, and therapy resistance. Understanding the intricate network underlying EV-mediated communication between tumor cells and adipocytes can provide critical insights into the mechanisms driving cancer cachexia. This review consolidates current knowledge on the crosstalk between tumor cells and adipose tissue mediated by EVs and offers valuable insights for future research. It also addresses controversial topics in the field and possible therapeutic approaches to manage cancer cachexia and ultimately improve patient outcomes and quality of life.

Cocoa extract induces browning of white adipocytes and improves glucose intolerance in mice fed a high-fat diet.

Cocoa extract (CE) offers several health benefits, such as anti-obesity and improved glucose intolerance. However, the mechanisms remain unclear. Adipose tissue includes white adipose tissue (WAT) and brown adipose tissue. Brown adipose tissue leads to body fat reduction by metabolizing lipids to heat via uncoupling protein 1 (UCP1). The conversion of white adipocytes into brown-like adipocytes (beige adipocytes) is called browning, and it contributes to the anti-obesity effect and improved glucose tolerance. This study aimed to evaluate the effect of CE on glucose tolerance in terms of browning. We found that dietary supplementation with CE improved glucose intolerance in mice fed a high-fat diet, and it increased the expression levels of Ucp1 and browning-associated gene in inguinal WAT. Furthermore, in primary adipocytes of mice, CE induced Ucp1 expression through β3-adrenergic receptor stimulation. These results suggest that dietary CE improves glucose intolerance by inducing browning in WAT.

Carnosic Acid (CA) Induces a Brown Fat-like Phenotype, Increases Mitochondrial Biogenesis, and Activates AMPK in 3T3-L1 Adipocytes.

Adipose tissue plays a crucial role in regulating metabolic homeostasis, and its dysfunction in obesity leads to insulin resistance and type 2 diabetes (T2D). White adipose tissue (WAT) primarily stores energy as lipids, while brown adipose tissue (BAT) regulates thermogenesis by dissipating energy as heat. The process of browning involves the transdifferentiation of WAT into brown-like or beige adipocytes, which exhibit a similar phenotype as BAT. The browning of WAT is an attractive approach against obesity and T2D, and the activation of the energy sensor AMP-activated protein kinase (AMPK) has been shown to play a role in browning. Carnosic acid (CA), a polyphenolic diterpene, found in many plants including rosemary, is reported to possess potent antioxidant, anti-inflammatory, and anti-hyperglycemic properties. The limited evidence available indicates that CA activates AMPK and may have anti-obesity and antidiabetic potential; however, the effects in adipocyte browning remain largely unexplored. This study aimed to examine the effects of CA on the markers of adipocyte browning. The treatment of 3T3L1 adipocytes with CA activated AMPK, reduced lipid accumulation, and increased the expression of browning protein markers (UCP-1, PGC-1α, PRDM16, and TFAM) and mitochondrial biogenesis. The use of compound C, an AMPK inhibitor, significantly attenuated the effects of CA, indicating AMPK involvement. These studies demonstrate that CA can activate AMPK and stimulate the browning of white adipocytes. Future animal and human studies are required to examine the effects of CA in vivo.

The autophagic regulation of rosiglitazone-promoted adipocyte browning.

Objective: Browning of white adipocytes is considered an efficient approach to combat obesity. Rosiglitazone induces the thermogenetic program of white adipocytes, but the underlying mechanisms remain elusive. Methods: Expression levels of browning and autophagy flux markers were detected by real-time PCR and immunoblotting. H&E and Oil Red O staining were performed to evaluate the lipid droplets area. Nuclear protein extraction and immunoprecipitation were used to detect the proteins interaction. Results: In this study, we reported that rosiglitazone promoted adipocyte browning and inhibited autophagy. Rapamycin, an autophagy inducer, reversed adipocyte browning induced by rosiglitazone. Autophagy inhibition by rosiglitazone does not prevent mitochondrial clearance, which was considered to promote adipose whitening. Instead, autophagy inhibition increased p62 nuclear translocation and stabilized the PPARγ-RXRα heterodimer, which is an essential transcription factor for adipocyte browning. We found that rosiglitazone activated NRF2 in mature adipocytes. Inhibition of NRF2 by ML385 reversed autophagy inhibition and the pro-browning effect of rosiglitazone. Conclusion: Our study linked autophagy inhibition with rosiglitazone-promoted browning of adipocytes and provided a mechanistic insight into the pharmacological effects of rosiglitazone.

A quick paster type of soluble nanoparticle microneedle patch for the treatment of obesity

Obesity is a major public burden on the working population and induces chronic diseases. Its treatment often requires long-term medication, which makes patient compliance difficult. In this study, we reported the value of HORN-MN, which comprised a fast-soluble hyaluronic acid microneedle matrix and a weak acid-degradable oleanolic acid dimer of rosiglitazone nanoparticles. The results showed that the microneedles easily punctured the stratum corneum and dissolved in the dermis of the abdominal wall within 5 min, followed by the release of rosiglitazone nanoparticles. Thereafter, the nanoparticles were endocytosed by macrophages and white adipocytes, then degraded to oleanolic acid in the lysosomes, thereby, releasing rosiglitazone. Oleanolic acid significantly improved the inflammatory status of obese adipose tissue and promoted white adipocyte browning, and rosiglitazone significantly potentiated WAC browning. Accordingly, the patch demonstrated a remarkable obesity-reducing efficacy in mice. In conclusion, this study developed a quick paster type of soluble rosiglitazone nanoparticle microneedle for the treatment of obesity. This patch can be suitable for working people, with an evident obesity-reducing efficacy but no effect on skin integrity despite multiple administrations.

Potential Role of Pig UCP3 in Modulating Adipocyte Browning via the Beta-Adrenergic Receptor Signaling Pathway.

Adipose tissue plays an important role in regulating body temperature and metabolism, with white adipocytes serving as storage units for energy. Recent research focused on the browning of white adipocytes (beige adipocytes), causing thermogenesis and lipolysis. The process of browning is linked to the activation of uncoupling protein (UCP) expression, which can be mediated by the β3 adrenergic receptor pathway. Transcriptional factors, such as peroxisome proliferator activated receptor γ (PPARγ) and PPARγ coactivator 1 alpha, play vital roles in cell fate determination for fat cells. Beige adipocytes have metabolic therapeutic potential to combat diseases such as obesity, diabetes mellitus, and dyslipidemia, owing to their significant impact on metabolic functions. However, the molecular mechanisms that cause the induction of browning are unclear. Therefore, research using animal models and primary culture is essential to provide an understanding of browning for further application in human metabolic studies. Pigs have physiological similarities to humans; hence, they are valuable models for research on adipose tissue. This study demonstrates the browning potential of pig white adipocytes through primary culture experiments. The results show that upregulation of UCP3 gene expression and fragmentation of lipid droplets into smaller particles occur due to isoproterenol stimulation, which activates beta-adrenergic receptor signaling. Furthermore, PPARγ and PGC-1α were found to activate the UCP3 promoter region, similar to that of UCP1. These findings suggest that pigs undergo metabolic changes that induce browning in white adipocytes, providing a promising approach for metabolic research with potential implications for human health. This study offers valuable insights into the mechanism of adipocyte browning using pig primary culture that can enhance our understanding of human metabolism, leading to cures for commonly occurring diseases.

NDUFA9 and its crotonylation modification promote browning of white adipocytes by activating mitochondrial function in mice

Protein crotonylation plays a role in regulating cellular metabolism, gene expression, and other biological processes. NDUFA9 (NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9) is closely associated with the activity and function of mitochondrial respiratory chain complex I. Mitochondrial function and respiratory chain are closely related to browning of white adipocytes, it’s speculated that NDUFA9 and its crotonylation are associated with browning of white adipocytes. Firstly, the effect of NDUFA9 on white adipose tissue was verified in white fat browning model mice, and it was found that NDUFA9 promoted mitochondrial respiration, thermogenesis, and browning of white adipose tissue. Secondly, in cellular studies, it was discovered that NDUFA9 facilitated browning of white adipocytes by enhancing mitochondrial function, mitochondrial complex I activity, ATP synthesis, and mitochondrial respiration. Again, the level of NDUFA9 crotonylation was increased by treating cells with vorinostat (SAHA)+sodium crotonate (NaCr) and overexpressing NDUFA9, it was found that NDUFA9 crotonylation promoted browning of white adipocytes. Meanwhile, the acetylation level of NDUFA9 was increased by treating cells with SAHA+sodium acetate (NaAc) and overexpressing NDUFA9, the assay revealed that NDUFA9 acetylation inhibited white adipocytes browning. Finally, combined with the competitive relationship between acetylation and crotonylation, it was also demonstrated that NDUFA9 crotonylation promoted browning of white adipocytes. Above results indicate that NDUFA9 and its crotonylation modification promote mitochondrial function, which in turn promotes browning of white adipocytes. This study establishes a theoretical foundation for the management and intervention of obesity, which is crucial in addressing obesity and related medical conditions in the future.

The regulatory effects of electroacupuncture on type 2 innate lymphoid cell (ILC2) function and browning of white adipose tissue in obese rats: 电针通过调控ILC2功能和白色脂肪棕色化治疗肥胖大鼠的作用机制

ObjectiveTo observe the effects of electroacupuncture (EA) on type 2 innate lymphoid cell (ILC2) function in white adipose tissue (WAT) of high-fat diet (HFD)-induced obese rats to reveal the mechanism underlying weight loss. MethodsMale Winstar rats (n=15) were randomly divided into control, HFD, and HFD+EA groups, with five rats in each group. An obesity model was established by feeding rats with a HFD. EA (2 Hz, 1 mA) was applied to “Zhongwan (CV12)” bilateral “Tianshu (ST25)” “Zusanli (ST36)” and “Sanyinjiao (SP6)” for 15 min, 7 days a week, for a total of 5 weeks. During EA treatment, the HFD group was fed a HFD, whereas rats in the control group were maintained on a normal diet. There was no intervention in either the control or the HFD groups. Body weight was measured weekly. Full-field adipocyte morphology, adipocyte volume, and the number of abdominal WAT were observed under a microscope after sectioning and hematoxylin and eosin staining. The levels of IL-5 (interleukin-5), IL-13 (interleukin-13), IL-33 (interleukin-33), and ST2 (growth stimulating gene 2 protein) in the WAT were assayed using enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction (RT-PCR). The expression levels of browning markers including PGC1α（peroxisome proliferator-activated receptor gamma coactivator 1-alpha）, PPARγ (peroxisome proliferator-activated receptor gamma), PRDM16 (histone-lysine N-methyltransferase), and UCP1（uncoupling protein 1 in WAT were detected by western blot analysis and RT-PCR. ResultsAfter a 7-week induction period, rats in both the HFD and HFD+EA groups were 20% heavier than their initial weights before modeling (P<0.01, P<0.001). Following a 5-week EA intervention, the body mass and Lee index of obese rats were significantly reduced (P<0.05). The HE results showed that adipocytes in the HFD group displayed a significant increase in diameter and a decrease in number compared to the control group. However, in the HFD+EA group, white adipocytes exhibited reduced diameter and appeared more regular in shape. In the control group, the proportion of ILC2 was (86.53±2.55)%, whereas in the HFD group, it decreased to (73.62±2.52)%, indicating a significant reduction in ILC2 in the WAT of obese rats. Following EA treatment, the proportion of ILC2 was elevated to (80.54±4.25)%. This analysis revealed a significant decrease in the expression levels of IL-5, IL-13, IL-33, and ST2 in the WAT of obese rats in the HFD group; however, these levels increased after EA intervention. The mRNA levels of PPARγ, PGC1α, PRDM16, and protein levels of UCP1 were decreased in the HFD group (P<0.01, P<0.05, and P<0.001), and the trends were significantly reversed with EA manipulation (P<0.05). RT-PCR and western blotting results revealed that EA remarkably upregulated the mRNA expression of PGC1α, PPARγ, and PRDM16, as well as the protein expression of UCP1 induced by HFD. In the HFD group, PRDM16 expression showed a strong correlation with UCP1 expression, and ILCs were strongly correlated with PGC1α expression. However, these strong correlations did not occur in HFD+EA group. Following EA treatment, the expression of PPARγ displayed a strong correlation with ILC2s, indicating that the altered ILC2 proportion was closely related to browning in WAT. ConclusionEA treatment effectively alleviated obesity by restoring ILC2 function and promoting browning of white adipocytes. ILC2s may play an important role in the effects of EA treatment, but this requires further study.

The dairy-derived peptide Miltin exerts anti-obesity effects by increasing adipocyte thermogenesis.

Growing research has highlighted that the consumption of dairy products improves the metabolic health in obese individuals by functioning as regulatory modulators. However, the molecular basis of this effect remains largely unknown. Herein, we report a dairy-derived peptide, which we named Miltin, that activates the thermogenesis of brown adipocytes and increases white adipocyte browning. Previously, Miltin was merely identified for its antioxidant capacity, although it is commonly present in different dairy products. In this study, we revealed the effect of Miltin in modulating adipose thermogenesis and further explored its potential in treating obesity through in vivo and in vitro strategies. The administration of Miltin in mice fed with a high-fat diet resulted in enhanced thermogenesis, improved glucose homeostasis, and reduced body mass and lipid accumulation, indicating the anti-obesity effect of Miltin. Genomic analysis revealed that Miltin modulates thermogenesis by inducing the activation of the MAPK signaling pathway by preferentially interacting with GADD45γ to promote its stability. Together, our findings indicate that Miltin's role in initiating the thermogenesis of adipocytes makes it a potential anti-obesity therapy for future development.

Regulatory mechanism of white adipocyte browning and research advances

Regulatory mechanism of white adipocyte browning and research advances

Caffeine-reinforced Collagen as Localized Microenvironmental Trans-Browning Bio-Matrix for Soft Tissue Repair and Regeneration in Bariatric Condition.

The wound exudates, hypoperfusion of the subcutaneous fat layer, and poor vasculature worsen wound management in obese subjects. In the current study, a multifunctional Caffeine-reinforced collagen biomaterial is developed that can simultaneously modulate lipid metabolism and angiogenesis in obese wound microenvironments for faster tissue regeneration. The biomaterial is fabricated specialized for obese conditions to initiate simultaneous lipolysis and angiogenesis locally in the hypoxic subcutaneous fat in wound margins of obese subjects. Caffeine-reinforced collagen biomatrix shows better structural integrity, thermal stability, bio-compatibility, and lesser proteolytic susceptibility. Caffeine-collagen biomaterial promote angiogenesis, fibroblast migration, and localized browning of white adipocytes to activate thermogenesis in the subcutaneous fat layer at the wound site. Full-thickness excision wound healing studies performed in obese C57BL6 mice shows faster wound closure within day 9 when compare to control mice. The Caffeine-reinforced collagen biomaterial remodeled the wound site locally by activating fibroblast to secrete collagen, activate endothelial cells to promote angiogenesis, and induce browning in white adipocytes in subcutaneous fat. The study opens a new direction in bariatric tissue regenerative medicine by locally modulating lipid metabolism, angiogenesis, and trans-browning at the injured site for faster complete restoration of the damaged tissue.

MiR-889-3p Facilitates the Browning Process of White Adipocyte Precursors by Targeting the SON Gene.

It is well-established that beige/brown adipose tissue can dissipate stored energy through thermogenesis; hence, the browning of white adipocytes (WAT) has garnered significant interest in contemporary research. Our preceding investigations have identified a marked downregulation of miR-889-3p concurrent with the natural maturation of brown adipose tissue. However, the specific role and underlying molecular mechanisms of miR-889-3p in the browning process of white adipose tissue warrant further elucidation. In this research, we initially delved into the potential role of miR-889-3p in preadipocyte growth via flow cytometry and CCK-8 assay, revealing that miR-889-3p can stimulate preadipocyte growth. To validate the potential contribution of miR-889-3p in the browning process of white adipose tissue, we established an in vitro rabbit white adipocyte browning induction, which exhibited a significant upregulation of miR-889-3p during the browning process. RT-qPCR and Western blot analysis indicated that miR-889-3p overexpression significantly amplified the mRNA levels of UCP1, PRDM16, and CIDEA, as well as UCP1 protein levels. Furthermore, miR-889-3p overexpression fostered intracellular triglyceride accumulation. Conversely, the downregulation of miR-889-3p hindered the browning of rabbit preadipocytes. Subsequently, based on target gene prediction and luciferase reporter gene determination, we demonstrated that miR-889-3p directly targets the 3'-UTR region of SON. Lastly, we observed that inhibiting SON could facilitate the browning of rabbit preadipocytes. In conclusion, our findings suggest that miR-889-3p facilitates the browning process of white adipocyte precursors by specifically targeting the SON gene.

Taraxacum mongolicum polysaccharide promotes white adipocyte browning by regulating miR-134-3p via Akt/GSK-3β signalling

In recent years, the incidence of obesity has gradually increased due to high calorie diets and lack of exercise. Reducing energy intake or increasing energy expenditure is the most effective way to promote weight loss and reduce lipid levels. Activated beige adipocytes can increase energy consumption in the body, and inducing conversion of white adipocytes to brown can prevent and treat obesity. Taraxacum mongolicum polysaccharide (TMP) is a plant polysaccharide that has been widely used for its anti-tumour and antioxidant properties. However, little is known about the role of TMP in the browning of sheep white adipose tissue. The aim of this study was to explore the potential mechanism of TMP and miR-134-3p in regulating the browning of sheep white adipocytes, as well as the regulatory relationship between TMP and miR-134-3p. Our results showed that TMP had a positive regulatory effect on the proliferation and browning of sheep white adipocytes. In addition, miR-134-3p significantly inhibited browning activity and AKT/GSK-3β signalling. Importantly, we found that TMP function required miR-134-3p mediation in the browning of sheep white adipocytes. Overall, our results suggested that TMP recruited beige adipocytes by regulating AKT/GSK-3β signalling via miR-134-3p.

Induction of Browning in White Adipocytes: Fucoidan Characterization and Gold Nanoparticle Synthesis from Undaria pinnatifida Sporophyll Extract.

Seaweed extracts and their specific polysaccharides are widely known for their ability to act as reducing and capping agents during nanoparticle synthesis. Their application is highly favored in green synthesis methods, owing to their eco-friendliness, cost-effectiveness, and remarkable time and energy efficiency. In this study, fucoidan extracted from Undaria pinnatifida sporophyll (UPS) is introduced as a polysaccharide that effectively serves as a dual-function reducing and capping agent for the synthesis of gold nanoparticles (AuNPs). Results from various analyses indicate that AuNPs derived from UPS extract display a uniform spherical shape with an average size of 28.34 ± 1.15 nm and a zeta potential of -37.49 ± 2.13 mV, conclusively confirming the presence of Au. The FT-IR spectra distinctly revealed the characteristic fucoidan bands on the stabilized UPS-AuNPs surface. A 1H-NMR analysis provided additional confirmation by revealing the presence of specific fucoidan protons on the UPS-AuNPs surface. To comprehensively evaluate the impact of UPS extract, UPS-AuNPs, and fucoidan on the biological properties of adipocytes, a rigorous comparative analysis of lipid droplet formation and morphology was conducted. Our findings revealed that adipocytes treated with UPS extract, fucoidan, and UPS-AuNPs, in that order, exhibited a reduction in the total lipid droplet surface area, maximum Ferret diameter, and overall Nile red staining intensity when compared to mature white adipocytes. Furthermore, our analysis of the effects of UPS extracts, UPS-AuNPs, and fucoidan on the expression of key markers associated with white adipose tissue browning, such as UCP1, PGC1a, and PRDM16, demonstrated increased mRNA and protein expression levels in the following order: UPS-AuNPs > fucoidan > UPS extracts. Notably, the production of active mitochondria, which play a crucial role in enhancing energy expenditure in beige adipocytes, also increased in the following order: UPS-AuNPs > fucoidan > UPS extract. These findings underscore the pivotal role of UPS extract, fucoidan, and UPS-AuNPs in promoting adipocyte browning and subsequently enhancing energy expenditure.

Modulation of angiogenic switch in reprogramming browning and lipid metabolism in white adipocytes

Thermogenic activation via trans-and de novo browning of white adipocytes is a promising strategy to accelerate lipid metabolism for regulating obesity-related disorders. In this study, we investigated the intricate interplay between angiogenic regulation and browning in white adipocytes using the bioactive compound, resveratrol (Rsv). Rsv has previously been documented for its regulatory influence on the trans and de novo browning of white adipocytes. Our findings revealed that concurrent activation of angiogenesis is prerequisite for inducing browning within the microenvironment of white adipocytes when exposed to browning activators. Additionally, we observed a significant browning effect on white adipocytes when the local adipose tissue environment was prompted to undergo angiogenesis, notably facilitated by a proangiogenic molecule known as Vascular endothelial growth factor (VEGF). Intriguingly, this effect was reversed when angiogenesis was inhibited by treatment with the antiangiogenic agent thalidomide. Furthermore, the study revealed the role of VEGF in paracrine activation of white adipocytes resulting in the induction of browning in both 3T3-L1 cell lines and primary mouse white adipocytes. The cross-talk between angiogenesis and browning was found to be initiated via the transcriptional activation of Estrogen receptor α (ERα) triggering the VEGF/VEGFR2 signaling pathway leading to browning and a reconfiguration of lipid metabolism within adipocytes. In conclusion, this study sheds light on the intricate cross-talk between angiogenesis and browning of white adipocytes. Notably, the findings underscore the reciprocal relationship between these processes, wherein inhibition of one process exerts discernible effects on the other.

TRPV4 in adipose tissue ameliorates diet-induced obesity by promoting white adipocyte browning

The induction of adipocyte browning to increase energy expenditure is a promising strategy to combat obesity. Transient receptor potential channel V4 (TRPV4) functions as a nonselective cation channel in various cells and plays physiological roles in osmotic and thermal sensations. However, the function of TRPV4 in energy metabolism remains controversial. This study revealed the role of TRPV4 in adipose tissue in the development of obesity. Adipose-specific TRPV4 overexpression protected mice against diet-induced obesity (DIO) and promoted white fat browning. TRPV4 overexpression was also associated with decreased adipose inflammation and improved insulin sensitivity. Mechanistically, TRPV4 could directly promote white adipocyte browning via the AKT pathway. Consistently, adipose-specific TRPV4 knockout exacerbated DIO with impaired thermogenesis and activated inflammation. Corroborating our findings in mice, TRPV4 expression was low in the white adipose tissue of obese people. Our results positioned TRPV4 as a potential regulator of obesity and energy expenditure in mice and humans.