Adipocyte Metabolism Research Articles

Aquaporins in GtoPdb v.2023.3

Aquaporins and aquaglyceroporins are membrane channels that allow the permeation of water and certain other small solutes across the cell membrane, or in the case of AQP6, AQP11 and AQP12A, intracellular membranes, such as vesicles and the endoplasmic reticulum membrane [16]. Since the isolation and cloning of the first aquaporin (AQP1) [20], 12 additional mammalian members of the family have been identified, although little is known about the functional properties of one of these (AQP12A; Q8IXF9) and it is thus not tabulated. The other 12 aquaporins can be broadly divided into three families: orthodox aquaporins (AQP0,-1,-2,-4,-5, -6 and -8) permeable mainly to water, but for some additional solutes [4]; aquaglyceroporins (AQP3,-7 -9 and -10), additionally permeable to glycerol and for some isoforms urea [14], and superaquaporins (AQP11 and 12) located within cells [12]. Some aquaporins also conduct ammonia and/or H2O2 giving rise to the terms 'ammoniaporins' ('aquaammoniaporins') and 'peroxiporins', respectively. Aquaporins are impermeable to protons and other inorganic and organic cations, with the possible exception of AQP1, although this is controversial [14]. One or more members of this family of proteins have been found to be expressed in almost all tissues of the body [reviewed in Yang (2017) [26]]. AQPs are involved in numerous processes that include systemic water homeostasis, adipocyte metabolism, brain oedema, cell migration and fluid secretion by epithelia. Loss of function mutations of some human AQPs, or their disruption by autoantibodies further underscore their importance [reviewed by Verkman et al. (2014) [23], Kitchen et al. (2105) [14]]. Functional AQPs exist as homotetramers that are the water conducting units wherein individual AQP subunits (each a protomer) have six TM helices and two half helices that constitute a seventh 'pseudotransmembrane domain' that surrounds a narrow water conducting channel [16]. In addition to the four pores contributed by the protomers, an additional hydrophobic pore exists within the center of the complex [16] that may mediate the transport through AQP1. Although numerous small molecule inhibitors of aquaporins, particularly APQ1, have been reported primarily from Xenopus oocyte swelling assays, the activity of most has subsequently been disputed upon retesting using assays of water transport that are less prone to various artifacts [5] and they are therefore excluded from the tables [see Tradtrantip et al. (2017) [22] for a review].

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.

RTN3 interacted with FABP5 and promoted lipid droplet biogenesis in cardiomyocytes

Abstract Background Lipid droplet (LD) accumulation is a notable feature of obesity-induced cardiomyopathy; however, detailed processes governing cardiac LD content remains poorly understood. Reticulon 3 (RTN3), a tubular endoplasmic reticulum (ER) localized protein, was recently identified as a key modulator of lipid metabolism in adipocytes. But its role in cardiac lipid metabolism and the specific mechanism of RTN3 regulating lipid content are currently unknown. Purpose To investigate the role of RTN3 in cardiac LD accumulation and the mechanism by which RTN3 affects LD metabolism. Methods We labelled LD, free fatty acids (FFA), and nucleus in cardiomyocytes with fluorescent markers and upregulated/downregulated RTN3 expression with adenovirus. The effect of RTN3 on cardiac LD content and biogenesis was detected with confocal microscopy. Then we investigated the interaction partner of RTN3 with co-immunoprecipitation (Co-IP), liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, and immunofluorescence staining. The function of the complex which RTN3 formed with its interaction protein was then explored. Results RTN3 overexpression significantly increased LD content in cardiomyocytes, which phenocopied the effects of palmitate stress. In contrast, palmitate-induced LD accumulation was blocked by RTN3 knockdown. Tubular ER, where RTN3 residents, is the primary organelle regulating LD biogenesis. Based on that, we hypothesized that the effect of RTN3 on LD content could be attributed to its direct effect on LD biogenesis in the ER. Further FFA tracing results demonstrated that RTN3 overexpression and palmitate could markedly increase FFA-LD colocalization, suggesting the LD biogenesis was activated, but this increase in colocalization was absent in cardiomyocytes infected with Ad sh-RTN3. Live cell imaging also revealed that upregulation of RTN3 significantly accelerated cardiac LD biogenesis and downregulation of RTN3 suppressed palmitate-induce LD biogenesis. Then we investigated the interaction partner of RTN3 and found that RTN3 formed a complex with fatty acids binding protein 5 (FABP5), which is an intracellular carrier for long-chain FFAs. Mechanistically, RTN3 directly bound with FABP5, which facilitated the directed transport of FFA to ER and thus promoted LD biogenesis. FABP5 knockdown blocked RTN3-mediated LD biogenesis. Moreover, we discovered that the 1st-194th amino acids of RTN3 was responsible for interacting with FABP5 and promoting LD biogenesis. Conclusions Our study reveals a novel mechanism contributing to LD biogenesis in cardiomyocytes. Based on our results, manipulating LD biogenesis by modulating RTN3 may be a potential strategy for treating LD accumulation in obese patients.RTN3 promoted lipid droplet biogenesisRTN3 formed a protein complex with FABP5

Naphthofuran Derivative BF4, A New Potent SIRT1 Activator, Regulates Lipid Metabolism in 3T3-L1 Adipocytes via the SIRT1-AMPK Pathway.

Our previously reported naphthofuran derivative BF4, identified as a potent silent information regulator 1 (SIRT1) activator, could alleviate high glucose stimulating apoptosis and inflammation response in human renal tubular epithelial (HK-2) cells. In this study, the underlying effects of BF4 on lipid metabolism in 3T3-L1 adipocytes were investigated. The effects of BF4 on pre-adipocyte differentiation and adipocyte lipolysis were studied using oil red O staining and quantitative glycerol and triglyceride content assay kits. Moreover, the molecular mechanism of BF4 on adipogenesis and lipid metabolism in 3T3-L1 adipocytes was investigated by real-time quantitative PCR and Western blotting analysis. We found that compound BF4 significantly decreased adipogenesis and lipid accumulation and inhibited the differentiation of 3T3-L1 pre-adipocytes into adipocytes. Moreover, compound BF4 decreased the expressions of several key regulators in adipocyte differentiation, including C/EBPβ and PPARγ, and their downstream lipogenesis targets via the activation of the SIRT1/AMPK pathway. Our results demonstrated that the novel SIRT1 activator BF4 might be a potent candidate for regulating lipid metabolism.

Exercise to Combat the Effect of Insulin Resistance in PCOS: A Narrative Review

Abstract: PCOS is a complex multigenic condition influenced by significant epigenetic and environmental variables, including nutrition and lifestyle. IR is found in roughly 80% of obese women with PCOS and 30–40% of lean women. IR is an impairment of insulin to mediate metabolism in skeletal muscle, adipocytes and liver. Following weight gain, the severity of IR in women with PCOS increases. IR affects many PCOS women who are not overweight, and minor weight loss improves clinical results in those with near-normal body weight. The effect of exercise on IS is optimized through glucose transport and metabolism. Exercise is the first-line treatment for PCOS. Moderate intensity (60–70% VO2max; comparable to 75–80% HRmax) and high-intensity aerobic exercise (heart rate >80%) improves IR in women with PCOS. These exercises are performed for at least 30 minutes per session and 3–5 days per week. A single bout of exercise (2–72 hours postexercise) can improve IS immediately. Exercise improves IS and glycemic management as well as helps in lowering the abdominal fat. Therefore, exercise performed on a regular basis can help improve insulin resistance in women with PCOS.

Advances in regulation of hypoxia on adipocyte development and lipid metabolism

The growth, differentiation and proliferation of adipose cells run through the whole life process. Dysregulation of lipid metabolism in adipose cells affects adipose tissue immunity and systemic energy metabolism. Increasingly available data suggest that lipid metabolism is involved in regulating the occurrence and development of various diseases, such as hyperlipidemia, nonalcoholic fatty liver disease, diabetes and cancer, which pose a major threat to human and animal health. Hypoxia inducible factor (HIF) is a major transcription factor mediating oxygen receptors in tissues and organs. HIF can induce disease by regulating lipid synthesis, fatty acid metabolism and lipid droplet formation. However, due to the difference of hypoxia degree, time and mode of action, there is no conclusive conclusion whether it has harmful or beneficial effects on the development of adipocytes and lipid metabolism. This article summarizes the regulation of hypoxia stress mediated transcription regulators and regulation of adipocyte development and lipid metabolism, aiming to reveal the potential mechanism of hypoxia induced changes in adipocyte metabolism pathways.

Lipocalin 2 regulates mitochondrial phospholipidome remodeling, dynamics, and function in brown adipose tissue in male mice

Mitochondrial function is vital for energy metabolism in thermogenic adipocytes. Impaired mitochondrial bioenergetics in brown adipocytes are linked to disrupted thermogenesis and energy balance in obesity and aging. Phospholipid cardiolipin (CL) and phosphatidic acid (PA) jointly regulate mitochondrial membrane architecture and dynamics, with mitochondria-associated endoplasmic reticulum membranes (MAMs) serving as the platform for phospholipid biosynthesis and metabolism. However, little is known about the regulators of MAM phospholipid metabolism and their connection to mitochondrial function. We discover that LCN2 is a PA binding protein recruited to the MAM during inflammation and metabolic stimulation. Lcn2 deficiency disrupts mitochondrial fusion-fission balance and alters the acyl-chain composition of mitochondrial phospholipids in brown adipose tissue (BAT) of male mice. Lcn2 KO male mice exhibit an increase in the levels of CLs containing long-chain polyunsaturated fatty acids (LC-PUFA), a decrease in CLs containing monounsaturated fatty acids, resulting in mitochondrial dysfunction. This dysfunction triggers compensatory activation of peroxisomal function and the biosynthesis of LC-PUFA-containing plasmalogens in BAT. Additionally, Lcn2 deficiency alters PA production, correlating with changes in PA-regulated phospholipid-metabolizing enzymes and the mTOR signaling pathway. In conclusion, LCN2 plays a critical role in the acyl-chain remodeling of phospholipids and mitochondrial bioenergetics by regulating PA production and its function in activating signaling pathways.

Dietary fructose-mediated adipocyte metabolism drives antitumor CD8+ T cell responses

Fructose consumption is associated with tumor growth and metastasis in mice, yet its impact on antitumor immune responses remains unclear. Here, we show that dietary fructose modulates adipocyte metabolism to enhance antitumor CD8+ Tcell immune responses and control tumor growth. Transcriptional profiling of tumor-infiltrating CD8+ Tcells reveals that dietary fructose mediates attenuated transition of CD8+ Tcells to terminal exhaustion, leading to a superior antitumor efficacy. High-fructose feeding initiates adipocyte-derived leptin production in an mTORC1-dependent manner, thereby triggering leptin-boosted antitumor CD8+ Tcell responses. Importantly, high plasma leptin levels are correlated with elevated plasma fructose concentrations and improved antitumor CD8+ Tcell responses in patients with lung cancer. Our study characterizes a critical role for dietary fructose in shaping adipocyte metabolism to prime antitumor CD8+ Tcell responses and highlights that the fructose-leptin axis may be harnessed for cancer immunotherapy.

Human visceral adipose tissue microvascular endothelial cell isolation and establishment of co-culture with white adipocytes to analyze cell-cell communication

Communication between adipocytes and endothelial cells (EC) is suggested to play an important role in the metabolic function of white adipose tissue. In order to generate tools to investigate in detail the physiology and communication of EC and adipocytes, a method for isolation of adipose microvascular EC from visceral adipose tissue (VAT) biopsies of subjects with obesity was developed. Moreover, mature white adipocytes were isolated from the VAT biopsies by a method adapted from a previously published Membrane aggregate adipocytes culture (MAAC) protocol. The identity and functionality of the cultivated and isolated adipose microvascular EC (AMvEC) was validated by imaging their morphology, analyses of mRNA expression, fluorescence activated cell sorting (FACS), immunostaining, low-density lipoprotein (LDL) uptake, and in vitro angiogenesis assays. Finally, we established a new trans filter co-culture system (membrane aggregate adipocyte and endothelial co-culture, MAAECC) for the analysis of communication between the two cell types. EC-adipocyte communication in this system was validated by omics analyses, revealing several altered proteins belonging to pathways such as metabolism, intracellular transport and signal transduction in adipocytes co-cultured with AMvEC. In reverse experiments, induction of several pathways including endothelial development and functions was found in AMvEC co-cultured with adipocytes. In conclusion, we developed a robust method to isolate EC from small quantities of human VAT. Furthermore, the MAAECC system established during the study enables one to study the communication between primary white adipocytes and EC or vice-versa and could also be employed for drug screening.

Effects of myostatin gene knockout on white fat browning and related gene expression in type 2 diabetic mice.

Myostatin (Mstn) plays an important role in adipocyte growth, differentiation and metabolism, leading to the development of obesity. We aimed to explore the effect of Mstn on white fat browning in a mouse model of type 2 diabetes mellitus (T2DM). Twelve wild-type (WT), 12 heterozygous (Mstn(+/-)) and 12 homozygous (Mstn(-/-)) male mice were randomly divided into 6 groups: WT, Mstn(+/-), Mstn(-/-), WT+DM, Mstn(+/-)+DM, and Mstn(-/-)+DM. The first 3 groups were fed normal chow, while the last 3 were fed high-fat diet and administered streptozotocin to generate T2DM. Subsequently, body mass, length, and white and brown fat masses were measured, after which Lee's index, white-brown ratio and fat index were calculated. The serum free fatty acid (FFA) levels were detected using enzyme-linked immunosorbent assay (ELISA). Hematoxylin and eosin (H&E) staining was used to analyze white and brown fat cell morphology. The relative expression levels of peroxisome proliferator-activated receptor-gamma (PPARγ), peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α), uncoupling protein 1 (UCP1), and cluster of differentiation 137 (CD137) protein were determined with western blotting. The Mstn(-/-) group displayed higher levels of PPARγ, PGC-1α and CD137 proteins in white and brown fat compared to the WT and Mstn(+/-) groups, while the expression level of UCP1 protein in the Mstn(-/-) group was higher than in the WT group. The expression levels of PPARγ, PGC-1α, UCP1, and CD137 proteins in the WT+DM group were lower than in the WT group. Moreover, PPARγ, PGC-1α, UCP1, and CD137 proteins were more highly expressed in the Mstn(-/-)+DM group compared to the WT+DM and Mstn(+/-)+DM groups. The Mstn gene inhibition antagonizes obesity phenotypes, such as white fat accumulation and lipid metabolism derangement caused by T2DM, thus promoting white fat browning.

Four-and-a-Half LIM-Domain Protein 2 (FHL2) Induces Neuropeptide Y (NPY) in Macrophages in Visceral Adipose Tissue and Promotes Diet-Induced Obesity.

Obesity is characterized by the expansion of the adipose tissue, usually accompanied by inflammation, with a prominent role of macrophages infiltrating the visceral adipose tissue (VAT). This chronic inflammation is a major driver of obesity-associated comorbidities. Four-and-a-half LIM-domain protein 2 (FHL2) is a multifunctional adaptor protein that is involved in the regulation of various biological functions and the maintenance of the homeostasis of different tissues. In this study, we aimed to gain new insights into the expression and functional role of FHL2 in VAT in diet-induced obesity. We found enhanced FHL2 expression in the VAT of mice with Western-type diet (WTD)-induced obesity and obese humans and identified macrophages as the cellular source of enhanced FHL2 expression in VAT. In mice with FHL2 deficiency (FHL2KO), WTD feeding resulted in reduced body weight gain paralleled by enhanced energy expenditure and uncoupling protein 1 (UCP1) expression, indicative of activated thermogenesis. In human VAT, FHL2 was inversely correlated with UCP1 expression. Furthermore, macrophage infiltration and the expression of the chemokine MCP-1, a known promotor of macrophage accumulation, was significantly reduced in WTD-fed FHL2KO mice compared with wild-type (wt) littermates. While FHL2 depletion did not affect the differentiation or lipid metabolism of adipocytes in vitro, FHL2 depletion in macrophages resulted in reduced expressions of MCP-1 and the neuropeptide Y (NPY). Furthermore, WTD-fed FHL2KO mice showed reduced NPY expression in VAT compared with wt littermates, and NPY expression was enhanced in VAT resident macrophages of obese individuals. Stimulation with recombinant NPY induced not only UCP1 expression and lipid accumulation but also MCP-1 expression in adipocytes. Collectively, these findings indicate that FHL2 is a positive regulator of NPY and MCP-1 expression in macrophages and herewith closely linked to the mechanism of obesity-associated lipid accumulation and inflammation in VAT. Thus, FHL2 appears as a potential novel target to interfere with the macrophage-adipocyte crosstalk in VAT for treating obesity and related metabolic disorders.

Impact of Oral Administration of Lactiplantibacillus plantarum Strain CNCM I-4459 on Obesity Induced by High-Fat Diet in Mice.

Recent evidence suggests that some lactobacilli strains, particularly Lactiplantibacillus plantarum, have a beneficial effect on obesity-associated syndromes. Several studies have investigated probiotic challenges in models of high-fat diet (HFD)-induced obesity, specifically with respect to its impact on hepatic and/or adipocyte metabolism, gut inflammation and epithelial barrier integrity, and microbiota composition. However, only a few studies have combined these aspects to generate a global understanding of how probiotics exert their protective effects. Here, we used the probiotic strain L. plantarum CNCM I-4459 and explored its impact on a mouse model of HFD-induced obesity. Briefly, mice were administered 1 × 109 CFUs/day and fed HFD for 12 weeks. Treatment with this strain improved insulin sensitivity by lowering serum levels of fasting glucose and fructosamine. Administration of the probiotic also affected the transport and metabolism of glucose, resulting in the downregulation of the hepatic Glut-4 and G6pase genes. Additionally, L. plantarum CNCM I-4459 promoted a decreased concentration of LDL-c and modulated hepatic lipid metabolism (downregulation of Fasn, Plin, and Cpt1α genes). Probiotic treatment also restored HFD-disrupted intestinal microbial composition by increasing microbial diversity and lowering the ratio of Firmicutes to Bacteroidetes. In conclusion, this probiotic strain represents a potential approach for at least partial restoration of the glucose sensitivity and lipid disruption that is associated with obesity.

Extracellular Vimentin Alters Energy Metabolism And Induces Adipocyte Hypertrophy.

Previous studies have reported that oxidative stress contributes to obesity characterized by adipocyte hypertrophy. However, mechanism has not been studied extensively. In the current study, we evaluated role of extracellular vimentin secreted by oxidized low-density lipoprotein (oxLDL) in energy metabolism in adipocytes. We treated 3T3-L1-derived adipocytes with oxLDL and measured vimentin which was secreted in the media. We evaluated changes in uptake of glucose and free fatty acid, expression of molecules functioning in energy metabolism, synthesis of adenosine triphosphate (ATP) and lactate, markers for endoplasmic reticulum (ER) stress and autophagy in adipocytes treated with recombinant vimentin. Adipocytes secreted vimentin in response to oxLDL. Microscopic evaluation revealed that vimentin treatment induced increase in adipocyte size and increase in sizes of intracellular lipid droplets with increased intracellular triglyceride. Adipocytes treated with vimentin showed increased uptake of glucose and free fatty acid with increased expression of plasma membrane glucose transporter type 1 (GLUT1), GLUT4, and CD36. Vimentin treatment increased transcription of GLUT1 and hypoxia-inducible factor 1α (Hif-1α) but decreased GLUT4 transcription. Adipose triglyceride lipase (ATGL), peroxisome proliferator-activated receptor γ (PPARγ), sterol regulatory element-binding protein 1 (SREBP1), diacylglycerol O-acyltransferase 1 (DGAT1) and 2 were decreased by vimentin treatment. Markers for ER stress were increased and autophagy was impaired in vimentin-treated adipocytes. No change was observed in synthesis of ATP and lactate in the adipocytes treated with vimentin. We concluded that extracellular vimentin regulates expression of molecules in energy metabolism and promotes adipocyte hypertrophy. Our results show that vimentin functions in the interplay between oxidative stress and metabolism, suggesting a mechanism by which adipocyte hypertrophy is induced in oxidative stress.

Combining different ion-selective channelrhodopsins to control water flux by light

Water transport through water channels, aquaporins (AQPs), is vital for many physiological processes including epithelial fluid secretion, cell migration and adipocyte metabolism. Water flux through AQPs is driven by the osmotic gradient that results from concentration differences of solutes including ions. Here, we developed a novel optogenetic toolkit that combines the light-gated anion channel GtACR1 either with the light-gated K+ channel HcKCR1 or the new Na+ channelrhodopsin HcNCR1 with high Na+ permeability, to manipulate water transport in Xenopus oocytes non-invasively. Water efflux through AQP was achieved by light-activating K+ and Cl- efflux through HcKCR1 and GtACR1. Contrarily, when GtACR1 was co-expressed with HcNCR1, inward movement of Na+ and Cl- was light-triggered, and the resulting osmotic gradient led to water influx through AQP1. In sum, we demonstrate a novel optogenetic strategy to manipulate water movement into or out of Xenopus oocytes non-invasively. This approach provides a new avenue to interfere with water homeostasis as a means to study related biological phenomena across cell types and organisms.

Adipose Tissues from Human and Bat-Derived Cell Lines Support Ebola Virus Infection.

Ebola virus is a zoonotic pathogen with a geographic range covering diverse ecosystems that are home to many potential reservoir species. Although researchers have detected Ebola virus RNA and serological evidence of previous infection in different rodents and bats, the infectious virus has not been isolated. The field is missing critical knowledge about where the virus is maintained between outbreaks, either because the virus is rarely encountered, overlooked during sampling, and/or requires specific unknown conditions that regulate viral expression. This study assessed adipose tissue as a previously overlooked tissue capable of supporting Ebola virus infection. Adipose tissue is a dynamic endocrine organ helping to regulate and coordinate homeostasis, energy metabolism, and neuroendocrine and immune functions. Through in vitro infection of human and bat (Eptesicus fuscus) brown adipose tissue cultures using wild-type Ebola virus, this study showed high levels of viral replication for 28 days with no qualitative indicators of cytopathic effects. In addition, alterations in adipocyte metabolism following long-term infection were qualitatively observed through an increase in lipid droplet number while decreasing in size, a harbinger of lipolysis or adipocyte browning. The finding that bat and human adipocytes are susceptible to Ebola virus infection has important implications for potential tissue tropisms that have not yet been investigated. Additionally, the findings suggest how the metabolism of this tissue may play a role in pathogenesis, viral transmission, and/or zoonotic spillover events.

Identification of potential molecular mechanisms and therapeutic targets for recurrent pelvic organ prolapse

BackgroundThe pathogenesis of recurrent pelvic organ prolapse (POP) is currently unclear. Therefore, developing targeted preventive measures is difficult. This study identified potential key pathways, crucial genes, comorbidities, and therapeutic targets associated with the occurrence and development of recurrent POP. MethodsThe original microarray data GSE28660, GSE53868, and GSE12852 were downloaded from the GEO database. Identification and validation of differentially expressed genes (DEGs) and hub genes associated with recurrent POP were performed using R software and cytoHubba of Cytoscape. Protein–protein interaction (PPI) networks were constructed using the STRING tool and visualized using Cytoscape. Gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) enrichment analyses were effectively performed using DAVID platforms. In addition, the NetworkAnalyst platform was used to explore and visualize the miRNA–hub gene network, TF–hub gene network, hub gene–disease network, and hub gene–drug/chemical network. ResultsA total of 110 DEGs and 6 hub genes (ADIPOQ, IL6, PPARG, CEBPA, LPL, and LIPE) were identified in this study. These genes were primarily enriched in the PPAR, AMPK, and adipocytokine, non-alcoholic fatty liver disease, and signaling pathways related to glycerol metabolism. Moreover, 96 miRNAs and 97 TFs were identified to as being associated with recurrent POP. These genes were closely linked to adipocyte metabolism and distribution, energy metabolism, and the longevity regulatory pathway. In addition, 192 diseases or chronic complications were potentially related to the recurrence of POP, including diabetes, hypertension, obesity, inflammatory diseases, and chronic obstructive pulmonary disease. Furthermore, 954 drugs or compounds were shown to have therapeutic potential for recurrent POP, and the most critical target drugs were dexamethasone, bisphenol A, efavirenz, 1-methyl-3-isobutylxanthine, and estradiol. ConclusionsThe results of this study revealed that ADIPOQ, IL6, PPARG, CEBPA, LPL, and LIPE as potential hub genes associated with recurrent POP, and these hub genes may aid in the understanding of the mechanism underlying POP recurrence and the development of potential molecular drugs.

Salacia reticulata Extract Suppresses Fat Accumulation by Regulating Lipid Metabolism.

The excessive storage of triglycerides in adipose tissue is a characteristic feature of obesity, which arises from an imbalance between energy intake and expenditure. In this study, we aimed to explore the potential anti-obesity effects of Salacia reticulata extracts (SC) in a high-fat diet (HFD)-induced in obese mice and 3T3-L1 adipocytes, with a specific focus on understanding the underlying lipid mechanisms. Mice were fed with a normal diet (NC; normal control), HFD (60% high-fat diet), Met (HFD containing metformin 250 mg/kg b.w.), SC25 (HFD containing SC 25 mg/kg b.w.), SC50 (HFD containing SC 50 mg/kg b.w.), or SC 100 (HFD containing SC 100 mg/kg b.w.) for 12 weeks. Notably, SC supplementation led to significant reductions in body weight gain, adipose tissue weight, adipose tissue mass, and adipocyte size in HFD-fed mice. Furthermore, SC supplementation exerted inhibitory effects on the adipogenesis and lipogenesis pathways while promoting lipolysis and thermogenesis pathways in the adipose tissues of HFD-fed mice. In vitro experiments using 3T3-L1 cells demonstrated that SC treatment during the differentiation phase suppressed adipogenesis and lipogenesis, whereas SC treatment after differentiation, activated lipolysis and thermogenesis. Collectively, these findings indicate that SC exhibits a direct influence on the lipid metabolism of adipocytes, making it an effective candidate for weight loss interventions.

Anti-obesity potential of a yogurt functionalized with a CLNA-rich pomegranate oil

Pomegranate oil is rich in conjugated linolenic acids, compounds which have attracted attention due to their potential applicability in obesity management as they are capable of modulating leptin and adiponectin secretion and regulate fatty acids storage and glucose metabolism. Among the possible bioactive foodstuffs capable of delivering these bioactive compounds yogurts have shown potential. Thus, the purpose of this work was to develop functional yogurts through the addition of pomegranate oil either in its free or encapsulated (used as a protective strategy against oxidation and gastrointestinal tract passage) forms. To that end, the pomegranate oil (free and encapsulated) was incorporated in yogurt and the functional yogurt capacity to modulate hepatic lipid accumulation, adipocyte metabolism (in terms of lipolysis, and adipokines secretion) and immune response was evaluated. The results obtained showed that the pomegranate oil’s incorporation led to an improvement in the yogurts' nutritional values, with a reduction in its atherogenic and thrombogenic indexes (more than 78% for atherogenic and 76% for thrombogenic index) and an enhancement of its hypocholesterolemic/hypercholesterolemic ratio (more than 62%) when compared to the control yogurt. Furthermore, data also showed for the first time how these functional yogurts promoted modulation of metabolic processes post GIT as they were capable of reducing by 40% triglycerides accumulation in steatosis-induced Hep G2 cells and by 30 % in differentiated adipocytes. Moreover, samples also showed a capacity to modulate the leptin and adiponectin secretion (56 % of increase in adiponectin) and reduce the IL-6 secretion (ca 44%) and TNF-α (ca 12%) in LPS-stimulated cells. Thus, the CLNA-rich yogurt here developed showed potential as a viable nutraceutical alternative for obesity management.

Transcriptome-wide association study-derived genes as potential visceral adipose tissue-specific targets for type 2 diabetes.

This study aimed to assess the causal relationship between visceral obesity and type 2 diabetes and subsequently to screen visceral adipose tissue (VAT)-specific targets for type 2 diabetes. We examined the causal relationship between VAT and type 2 diabetes using bidirectional Mendelian randomisation (MR) followed by multivariable MR. We conducted a transcriptome-wide association study (TWAS) leveraging prediction models and a large-scale type 2 diabetes genome-wide association study (74,124 cases and 824,006 controls) to identify candidate genes in VAT and used summary-data-based MR (SMR) and co-localisation analysis to map causal genes. We performed enrichment and single-cell RNA-seq analyses to determine the cell-specific localisation of the TWAS-identified genes. We also conducted knockdown experiments in 3T3-L1 pre-adipocytes. MR analyses showed a causal relationship between genetically increased VAT mass and type 2 diabetes (inverse-variance weighted OR 2.48 [95% CI 2.21, 2.79]). Ten VAT-specific candidate genes were associated with type 2 diabetes after Bonferroni correction, including five causal genes supported by SMR and co-localisation: PABPC4 (1p34.3); CCNE2 (8q22.1); HAUS6 (9p22.1); CWF19L1 (10q24.31); and CCDC92 (12q24.31). Combined with enrichment analyses, clarifying cell-type specificity with single-cell RNA-seq data indicated that most TWAS-identified candidate genes appear more likely to be associated with adipocytes in VAT. Knockdown experiments suggested that Pabpc4 likely contributes to regulating differentiation and energy metabolism in 3T3-L1 adipocytes. Our findings provide new insights into the genetic basis and biological processes of the association between VAT accumulation and type 2 diabetes and warrant investigation through further functional studies to validate these VAT-specific candidate genes.

Regulatory effects of baicalin, a flavonoid compound, on adipocyte metabolism.

Baicalin is a plant-derived, biologically active compound exerting numerous advantageous effects. Adipocytes store and release energy in the process of lipogenesis and lipolysis. Rodent studies have shown that baicalin treatment positively affects fat tissue, however, data on the direct influence of this compound on adipocyte metabolism is lacking. In the present research, the short-term effects of 25, 50, and 100 μM baicalin on glucose transport, conversion to lipids, and oxidation, and also on lipolysis in primary rat adipocytes were explored. Lipolysis was measured as glycerol release from adipocytes. It was shown that 100 μM baicalin reduced glucose oxidation but at any concentration did not affect glucose transport and lipogenesis. Baicalin significantly increased the adipocyte response to physiological and pharmacological lipolytic stimuli (such as epinephrine - adrenergic agonist, DPCPX - adenosine A1 receptor antagonist, and amrinone - cAMP phosphodiesterase inhibitor). The stimulatory effects of baicalin on epinephrine-induced lipolysis were markedly diminished by insulin (activator of cAMP phosphodiesterases) and H-89 (PKA inhibitor). It was also demonstrated that baicalin evoked a similar rise in epinephrine-induced lipolysis in the presence of glucose and alanine. Our results provided evidence that baicalin may reduce glucose oxidation and is capable of enhancing lipolysis in primary rat adipocytes. The action on lipolysis is glucose-independent and covers both the adrenergic and adenosine A1 receptor pathways. The rise in cAMP content is proposed to be responsible for the observed potentiation of the lipolytic process.