High-fat Diet-induced Obese Mice Research Articles

Lactobacillus casei-fermented Amomum xanthioides ameliorates metabolic dysfunction in high-fat diet-induced obese mice.

Amomum xanthioides (AX) has been used as an edible herbal medicine to treat digestive system disorders in Asia. Additionally, Lactobacillus casei is a well-known probiotic commonly used in fermentation processes as a starter. The current study aimed to investigate the potential of Lactobacillus casei-fermented Amomum xanthioides (LAX) in alleviating metabolic disorders induced by high-fat diet (HFD) in a mouse model. LAX significantly reduced the body and fat weight, outperforming AX, yet without suppressing appetite. LAX also markedly ameliorated excessive lipid accumulation and reduced inflammatory cytokine (IL-6) levels in serum superior to AX in association with UCP1 activation and adiponectin elevation. Furthermore, LAX noticeably improved the levels of fasting blood glucose, serum insulin, and HOMA-IR through positive regulation of glucose transporters (GLUT2, GLUT4), and insulin receptor gene expression. In conclusion, the fermentation of AX demonstrates a pronounced mitigation of overnutrition-induced metabolic dysfunction, including hyperlipidemia, hyperglycemia, hyperinsulinemia, and obesity, compared to non-fermented AX. Consequently, we proposed that the fermentation of AX holds promise as a potential candidate for effectively ameliorating metabolic disorders.

Susceptibility to recombinant SARS-CoV-2 spike protein entry in the lungs of high-fat diet-induced obese mice.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Obesity is a major risk factor for the development of COVID-19. Angiotensin-converting enzyme 2 (ACE2) is an essential receptor for cell entry of SARS-CoV-2. The receptor-binding domain of the S1 subunit (S1-RBD protein) in the SARS-CoV-2 spike glycoprotein binds to ACE2 on host cells, through which the virus enters several organs, including the lungs. Considering these findings, recombinant ACE2 might be utilized as a decoy protein to attenuate SARS-CoV-2 infection. Here, we examined whether obesity increases ACE2 expression in the lungs and whether recombinant ACE2 administration diminishes the entry of S1-RBD protein into lung cells. We observed that high-fat diet-induced obesity promoted ACE2 expression in the lungs by increasing serum levels of LPS derived from the intestine. S1-RBD protein entered the lungs specifically through ACE2 expressed in host lungs and that the administration of recombinant ACE2 attenuated this entry. We conclude that obesity makes hosts susceptible to recombinant SARS-CoV-2 spike proteins due to elevated ACE2 expression in lungs, and this model of administering S1-RBD protein can be applied to new COVID-19 treatments.

Statin administration or blocking PCSK9 alleviates airway hyperresponsiveness and lung fibrosis in high-fat diet-induced obese mice

BackgroundObesity is associated with airway hyperresponsiveness and lung fibrosis, which may reduce the effectiveness of standard asthma treatment in individuals suffering from both conditions. Statins and proprotein convertase subtilisin/kexin-9 inhibitors not only reduce serum cholesterol, free fatty acids but also diminish renin-angiotensin system activity and exhibit anti-inflammatory effects. These mechanisms may play a role in mitigating lung pathologies associated with obesity.MethodsMale C57BL/6 mice were induced to develop obesity through high-fat diet for 16 weeks. Conditional TGF-β1 transgenic mice were fed a normal diet. These mice were given either atorvastatin or proprotein convertase subtilisin/kexin-9 inhibitor (alirocumab), and the impact on airway hyperresponsiveness and lung pathologies was assessed.ResultsHigh-fat diet-induced obesity enhanced airway hyperresponsiveness, lung fibrosis, macrophages in bronchoalveolar lavage fluid, and pro-inflammatory mediators in the lung. These lipid-lowering agents attenuated airway hyperresponsiveness, macrophages in BALF, lung fibrosis, serum leptin, free fatty acids, TGF-β1, IL-1β, IL-6, and IL-17a in the lung. Furthermore, the increased RAS, NLRP3 inflammasome, and cholecystokinin in lung tissue of obese mice were reduced with statin or alirocumab. These agents also suppressed the pro-inflammatory immune responses and lung fibrosis in TGF-β1 over-expressed transgenic mice with normal diet.ConclusionsLipid-lowering treatment has the potential to alleviate obesity-induced airway hyperresponsiveness and lung fibrosis by inhibiting the NLRP3 inflammasome, RAS and cholecystokinin activity.Graphical abstract

Evaluate and compare the anti-obesity effects of two probiotic preparations in high-fat diet-induced obese mice

This study screened two probiotic preparations and comprehensively evaluated for anti-obesity efficacy in high-fat diet-induced obese mice. Obese mice were orally administered with low, medium, and high doses of AB-Kefir (ABK) or Lactiplantibacillus plantarum TWK10 (TWK), respectively. After 8 weeks of administration, medium doses and above of ABK and TWK significantly reduced body weight, white adipose tissue weight, serum glucose, and lipid levels and attenuated hepatic steatosis and adipocyte hypertrophy in obese mice without affecting appetite. ABK and TWK also decreased serum adipokine levels and increased the adiponectin/leptin ratio to ameliorate obesity-induced adipose tissue dysfunction and chronic inflammation. Moreover, ABK and TWK reduced adipogenesis/lipogenesis-related transcription factors and enzymes in adipose tissue and improved energy metabolism by activating the AMPK pathway. In particular, TWK showed superior anti-obesity activity compared to ABK. The outcomes of this study will help explore potential anti-obesity probiotic functional foods.

Resistant starch-enriched brown rice exhibits prebiotic properties and enhances gut health in obese mice

Resistant starch serves as a prebiotic in the large intestine, aiding in the maintenance of a healthy intestinal environment and mitigating associated chronic illnesses. This study aimed to investigate the impact of resistant starch-enriched brown rice (RBR) on intestinal health and functionality. We assessed changes in resistant starch concentration, structural alterations, and branch chain length distribution throughout the digestion process using an in vitro model. The efficacy of RBR in the intestinal environment was evaluated through analyses of its prebiotic potential, effects on intestinal microbiota, and intestinal function-related proteins in obese animals fed a high-fat diet. RBR exhibited a higher yield of insoluble fraction in both the small and large intestines compared to white and brown rice. The total digestible starch content decreased, while the resistant starch content significantly increased during in vitro digestion. Furthermore, RBR notably enhanced the growth of four probiotic strains compared to white and brown rice, displaying higher proliferation activity than the positive control, FOS. Notably, consumption of RBR by high-fat diet-induced obese mice suppressed colon shortening, increased Bifidobacteria growth, and improved intestinal permeability. These findings underscore the potential prebiotic and gut health-promoting attributes of RBR, offering insights for the development of functional foods aimed at preventing gastrointestinal diseases.

Fructooligosaccharides Intake during Pregnancy Improves Metabolic Phenotype of Offspring in High Fat Diet-Induced Obese Mice.

Obesity and metabolic diseases are closely associated, and individuals who become obese are also prone to type 2 diabetes and cardiovascular disorders. Gut microbiota is mediated by diet and can influence host metabolism and the incidence of metabolic disorders. Recent studies have suggested that improving gut microbiota through a fructooligosaccharide (FOS)-supplemented diet may ameliorate obesity and other metabolic disorders. Although accumulating evidence supports the notion of the developmental origins of health and disease, the underlying mechanisms remain obscure. ICR mice are fed AIN-93G formula-based cellulose -, FOS-, acetate-, or propionate-supplemented diets during pregnancy. Offspring are reared by conventional ICR foster mothers for 4 weeks; weaned mice are fed high fat diet for 12 weeks and housed individually. The FOS and propionate offspring contribute to suppressing obesity and improving glucose intolerance. Gut microbial compositions in FOS-fed mothers and their offspring are markedly changed. However, the beneficial effect of FOS diet on the offspring is abolished when antibiotics are administered to pregnant mice. The findings highlight the link between the maternal gut environment and the developmental origin of metabolic syndrome in offspring. These results open novel research avenues into preemptive therapies for metabolic disorders by targeting the maternal gut microbiota.

Anti-obesity potentiality of Lactiplantibacillus plantarum E2_MCCKT isolated from a fermented beverage, haria: a high fat diet-induced obese mice model study.

Obesity is a growing epidemic worldwide. Several pharmacologic drugs are being used to treat obesity but these medicines exhibit side effects. To find out the alternatives of these drugs, we aimed to assess the probiotic properties and anti-obesity potentiality of a lactic acid bacterium E2_MCCKT, isolated from a traditional fermented rice beverage, haria. Based on the 16S rRNA sequencing, the bacterium was identified as Lactiplantibacillus plantarum E2_MCCKT. The bacterium exhibited in vitro probiotic activity in terms of high survivability in an acidic environment and 2% bile salt, moderate auto-aggregation, and hydrophobicity. Later, E2_MCCKT was applied to obese mice to prove its anti-obesity potentiality. Adult male mice (15.39 ± 0.19g) were randomly divided into three groups (n = 5) according to the type of diet: normal diet (ND), high-fat diet (HFD), and HFD supplemented with E2_MCCKT (HFT). After four weeks of bacterial treatment on the obese mice, a significant reduction of body weight, triglyceride, and cholesterol levels, whereas, improvements in serum glucose levels were observed. The bacterial therapy led to mRNA up-regulation of lipolytic transcription factors such as peroxisome proliferator-activated receptor-α which may increase the expression of fatty acid oxidation-related genes such as acyl-CoA oxidase and carnitine palmitoyl-transferase-1. Concomitantly, both adipocytogenesis and fatty acid synthesis were arrested as reflected by the down-regulation of sterol-regulatory element-binding protein-1c, acetyl-CoA carboxylase, and fatty acid synthase genes. In protein expression study, E2_MCCKT significantly increased IL-10 expression while decreasing pro-inflammatory cytokine (IL-1Ra and TNF-α) expression. In conclusion, the probiotic Lp. plantarum E2_MCCKT might have significant anti-obesity effects on mice.

Identification of phenolic compounds from fermented Moringa oleifera Lam. leaf supplemented with Fuzhuan brick tea and their volatile composition and anti-obesity activity.

As a nutritious plant with valuable potential, the Moringa oleifera Lam. (MOL) leaf addition on Fuzhuan brick tea (FBT) for the co-fermentation (MOL-FBT) was an industry innovation and a new route to make full use of MOL leaf. After optimization of the extraction conditions, the best conditions for the polyphenols extraction method from MOL-FBT (MFP) were 60°C for 40min (1:80, V/W) using response surface methodology. A total of 30 phenolics were identified and quantified. Most of the polyphenols were increased after adding MOL leaf for co-fermentation compared to FBT polyphenols. In particular, caffeic acids were found only in MFP. Moreover, the MFP received high value in taste, aroma, and color. In total, 62 volatile flavor compounds, consisting of 3 acids, 5 alcohols, 15 aldehydes, 4 esters, 20 hydrocarbons, 10 ketones, and 5 others, were identified in MFP. In addition, MFP inhibited 3T3-L1 preadipocyte differentiation in a dose-dependent manner and decreased lipid accumulation via the peroxisome proliferator-activated receptor gamma (PPARγ)/CCAAT/enhancer binding protein alpha (CEBPα)/cluster of differentiation 36 (CD36) axis and induced a brown adipocyte-like phenotype. In vivo experiments were further conducted to confirm the in vitro results. MFP regulated lipid accumulation, glucose/insulin tolerance, improved liver and kidney function, and inhibited the secretion of pro-inflammatory factors by the PPARγ/CEBPα/CD36 axis and alleviated inflammation in high fat and high fructose diet-induced obese mice. In summary, MFP possesses high-quality properties and anti-obesity effects, as well as the great potential to be used as a novel functional food product.

Comparative analysis of anti-obesity effects of green, fermented, and γ-aminobutyric acid teas in a high-fat diet-induced mouse model

Obesity, a prevalent disease associated with numerous chronic conditions, including hyperlipidemia, hyperglycemia, diabetes, and metabolic syndrome, remains a major global health challenge. This study investigated the potential of green tea (GT), fermented tea (FT), and γ-aminobutyric acid (GABA) tea (GBT), which are rich in phytonutrients and polyphenols, for the management of obesity. Using a high-fat diet-induced obese mouse model (C57BL/6N), we explored the effect of these teas on various obesity-related parameters. The mice were categorized into five groups: normal diet with water, high-fat diet with water, and high-fat diet supplemented with GT, FT, or GBT. Over 13 weeks, we monitored body weight, perirenal and liver fat, adipocyte lipid accumulation, and key metabolic indicators, such as serum cholesterol, leptin, insulin, and fasting blood glucose. These teas contain beneficial phytochemicals such as GABA, theanine, and caffeine, and have demonstrated an enhanced antioxidant capacity, which increases the scavenging of free radicals and may reduce oxidative stress. The animal study indicated a decrease in feeding efficiency and significant reductions in body weight liver fat, epididymal fat, and perirenal fat, as well as in adipocyte lipid accumulation. Additionally, notable improvements were observed in metabolic health indicators, including reductions in serum cholesterol, leptin, insulin, and fasting blood glucose levels. Our findings revealed that GT, FT, or GBT significantly counteracted the negative effects of a high-fat diet, suggesting their potential in combating obesity and related metabolic disorders.

Capsaicin induces ATP-dependent thermogenesis via the activation of TRPV1/β3-AR/α1-AR in 3T3-L1 adipocytes and mouse model

Capsaicin (CAP) is a natural bioactive compound in chili pepper that activates the transient receptor potential vanilloid subfamily 1 (TRPV1) and is known to stimulate uncoupling protein 1 (UCP1)-dependent thermogenesis. However, its effect on ATP-dependent thermogenesis remains unknown. In this study, we employed qRT-PCR, immunoblot, staining method, and assay kit to investigate the role of CAP on ATP-dependent thermogenesis and its modulatory roles on the TRPV1, β3-adrenergic receptor (β3-AR), and α1-AR using in vitro and in vivo models. The studies showed that CAP treatment in high-fat diet-induced obese mice resulted in lower body weight gain and elevated ATP-dependent thermogenic effectors' protein and gene expression through ATP-consuming calcium and creatine futile cycles. In both in vitro and in vivo experiments, CAP treatment elevated the protein and gene expressions of sarcoendoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2), ryanodine receptor 2 (RYR2), creatine kinase B (CKB), and creatine kinase mitochondrial 2 (CKMT2) mediated by the activation of β3-AR, α1-AR, and TRPV1. Our study showed that CAP increased intracellular Ca2+ levels and the expression of voltage-dependent anion channel (VDAC) and mitochondrial calcium uniporter (MCU) which indicates that increased mitochondrial Ca2+ levels lead to increased expression of oxidative phosphorylation protein complexes as a result of ATP-futile cycle activation. A mechanistic study in 3T3-L1 adipocytes revealed that CAP induces UCP1- and ATP-dependent thermogenesis mediated by the β3-AR/PKA/p38MAPK/ERK as well as calcium-dependent α1-AR/TRPV1/CaMKII/AMPK/SIRT1 pathway. Taken together, we identified CAP's novel functional and modulatory roles in UCP1- and ATP-dependent thermogenesis, which is important for developing therapeutic strategies for combating obesity and metabolic diseases.

DA-6034 ameliorates hepatic steatosis and inflammation in high fat diet-induced obese mice.

Nonalcoholic fatty liver disease (NAFLD) is characterized by an increase in hepatic triglyceride content and increased inflammatory macrophage infiltration through the C-C motif chemokine receptor (CCR) 5 pathway in the liver. DA-6034 (7-carboxymethyloxy-3',4',5-trimethoxy flavone), is a synthetic derivative of eupatilin that exhibits anti-inflammatory activity in inflammatory bowel disease. However, the effect of DA-6034 on the inflammatory response in NAFLD is not well elucidated. Therefore, we aimed to determine the effect of DA-6034 on hepatic steatosis and inflammation. Forty male C57BL/6J mice were divided into the following four groups: (1) regular diet (RD), (2) RD with DA-6034, (3) high fat diet (HFD), and (4) HFD with DA-6034. All mice were sacrificed 12 weeks after the start of the experiment. The effects of DA-6034 on macrophages were assessed using RAW264.7 cells. DA-6034 not only reduced hepatic triglyceride levels and lipid accumulation but also macrophage infiltration and proinflammatory cytokines in HFD-fed mice. According to fluorescence-activated cell sorter analysis, DA-6034 reduced the CD8+ T cell fraction in the liver of HFD-fed mice. DA-6034 also reduced CCR5 expression and the migration of liver macrophages in HFD-fed mice and inhibited CCR2 ligand and CCR4 ligand, which stimulated the migration of macrophages. Overall, DA-6034 attenuates hepatic steatosis and inflammation in obesity by regulating CCR5 expression in macrophages.

Anti-Obesity Effect of Jeju Roasted Citrus Peel Extract in High-Fat Diet-Induced Obese Mice and 3T3-L1 Adipocytes Via Lipid Metabolism Regulation.

Lipid accumulation in adipocytes occurs through multifactorial effects such as overnutrition due to unbalanced eating habits, reduced physical activity, and genetic factors. In addition, obesity can be intensified by the dis-regulation of various metabolic systems such as differentiation, lipogenesis, lipolysis, and energy metabolism of adipocytes. In this study, the Jeju roasted peel extract from Citrus unshiu S.Markov. (JRC), which is discarded as opposed to the pulp of C. unshiu S.Markov., is commonly consumed to ameliorate obesity. To investigate the anti-obesity effect of JRC, these studies were conducted on differentiated 3T3-L1 cells and in high-fat diet-induced mice, and related methods were used to confirm whether it decreased lipid accumulation in adipocytes. The mechanism of inhibiting obesity by JRC was confirmed through mRNA expression studies. JRC suppressed lipid accumulation in adipocytes and adipose tissue, and significantly improved enzymes such as alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase and serum lipid profiles. In addition, it effectively modulated the expression of genes related to lipid and energy metabolism in adipose tissue. As a result, these findings suggest that JRC could be a therapeutic regulator of body fat accumulation by significantly alleviating the dis-regulation of intracellular lipid metabolism in adipocytes and by enhancement of energy metabolism (Approval No. CNU IACUC-YB-2023-98).

Anti-Obesity Effect and Signaling Mechanism of Potassium Poly-γ-Glutamate Produced by Bacillus subtilis Chungkookjang in High-Fat Diet-Induced Obese Mice.

The purpose of this work was to examine the effects of potassium poly-γ-glutamate (PGA-K) on mice fed a high-fat diet consisting of 60% of total calories for 12 weeks. PGA-K administration reduced the increase in body weight, epididymal fat, and liver weight caused by a high-fat diet compared to the obese group. The triglyceride, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels, which are blood lipid indicators, were significantly increased in the obese group but were significantly decreased in the PGA-K-treated group. The administration of PGA-K resulted in a significant inhibition of pro-inflammatory cytokines, including tumor necrosis factor α and interleukin 6. Moreover, the levels of leptin and insulin, which are insulin resistance indicators, significantly increased in the obese group but were significantly decreased in the PGA-K-treated group. These results suggest that PGA-K exhibits a protective effect against obesity induced by a high-fat diet, underscoring its potential as a candidate for obesity treatment.

Tipepidine activates AMPK and improves adipose tissue fibrosis and glucose intolerance in high-fat diet-induced obese mice.

Tipepidine (3-[di-2-thienylmethylene]-1-methylpiperidine) (TP) is a non-narcotic antitussive used in Japan. Recently, the potential application of TP in the treatment of neuropsychiatric disorders, such as depression and attention deficit hyperactivity disorder, has been suggested; however, its functions in energy metabolism are unknown. Here, we demonstrate that TP exhibits a metabolism-improving action. The administration of TP reduced high-fat diet-induced body weight gain in mice and lipid accumulation in the liver and increased the weight of epididymal white adipose tissue (eWAT) in diet-induced obese (DIO) mice. Furthermore, TP inhibited obesity-induced fibrosis in the eWAT. We also found that TP induced AMP-activated protein kinase (AMPK) activation in the eWAT of DIO mice and 3T3-L1 cells. TP-induced AMPK activation was abrogated by the transfection of liver kinase B1 siRNA in 3T3-L1 cells. The metabolic effects of TP were almost equivalent to those of metformin, an AMPK activator that is used as a first-line antidiabetic drug. In summary, TP is a potent AMPK activator, suggesting its novel role as an antidiabetic drug owing to its antifibrotic effect on adipose tissues.

Effects of beef fat enriched with trans vaccenic acid and cis9, trans11-CLA on glucose homoeostasis and hepatic lipid accumulation in high-fat diet-induced obese mice.

Trans vaccenic acid (TVA, trans11-18:1) and cis9, trans11-CLA (also known as rumenic acid; RA) have received widespread attention as potentially beneficial trans-FA due to their putative health benefits, including anti-diabetic properties. The objective of this study was to determine the effects of beef fat naturally enriched with TVA and RA on parameters related to glucose homoeostasis and associated metabolic markers in diet-induced obese (DIO) mice. Thirty-six male C57BL/6J mice (8 weeks old) were fed for 19 weeks with either a control low-fat diet (CLF), a control high-fat diet (CHF), or a TVA+RA-enriched high-fat diet (EHF). Compared with CLF, feeding either CHF or EHF resulted in adverse metabolic outcomes associated with high-fat diets, including adiposity, impaired glucose control and hepatic steatosis. However, the EHF diet induced a significantly higher liver weight TAG content and elevated plasma alanine transaminase levels compared with the CHF diet. Collectively, the findings from this study suggest that EHF does not improve glucose tolerance and worsens liver steatosis in DIO mice. However, the adverse effects of EHF on the liver could be in part related to the presence of other trans-FA in the enriched beef fat.

Sipyimigwanjung-tang, a traditional herbal medication, alleviates weight gain in a high-fat diet-induced obese mice model

Obesity leads to the development of metabolic syndrome and comorbidities. Overweight and obesity continue to be a relentless global issue. Sipyimigwanjung-tang (SGT), a traditional herbal medication, was first mentioned in Dongui Sasang Shinpyun and has been used to treat edema, meteorism, and jaundice, which are common findings associated with obesity. The main physiological feature of obesity is expanded adipose tissue, which causes several impairments in liver metabolism. Therefore, this study aimed to investigate the anti-obesity effects of SGT in the epididymal white adipose tissue (eWAT) and livers of high-fat diet (HFD)-induced obese mice. SGT significantly blocked HFD-induced weight gain in C57BL/6N mice. In addition, SGT effectively reduced the increased weight and adipocyte size in eWAT of HFD-induced obese C57BL/6 N mice. Moreover, SGT significantly decreased the elevated gene expression of Peroxisome proliferator-activated receptor γ, CCAAT/enhancer-binding protein α, and Sterol regulatory element-binding protein 1 in the eWAT of HFD-induced obese mice. Furthermore, SGT significantly decreased lipid accumulation in the livers of HFD-induced obese mice and differentiated 3T3-L1 adipocytes. Hence, the present study provides substantial evidence that SGT has potential therapeutic effects on obesity.

Hippocampal proteomic changes in high-fat diet-induced obese mice associated with memory decline

Substantial evidences suggest that chronic consumption of high-fat diets (HFDs) can lead to obesity, abnormal metabolism, as well as cognitive impairment. Molecular and cellular changes regarding hippocampal dysfunctions have been identified in multiple HFD animal models. Therefore, in-depth identification of expression changes of hippocampal proteins is critical for understanding the mechanism of HFD-induced cognitive deficits. In this study, we fed 3-week old male mice with HFD for 3 months to generate obese mice who exhibit systemic metabolic abnormality and learning and memory decline. Using an iTRAQ-labeled proteomic analysis, we identified a total of 82 differentially expressed proteins (DEPs) in the hippocampus upon HFD with 35 up-regulated proteins and 47 down-regulated proteins. Functional enrichment indicated that these DEPs were predominantly enriched in regulation of catabolic process, dendritic shaft, neuron projection morphogenesis and GTPase regulator activity. Protein-protein interaction enrichment showed that the DEPs are mostly enriched in postsynaptic functions; and of them, 6 proteins (i.e., DLG3, SYNGAP1, DCLK1, GRIA4, GRIP1 and AGHGAP32) were involved in several functional assemblies of the postsynaptic density including G-protein signaling, scaffolding and adaptor, kinase and AMPA signaling, respectively. Collectively, our findings suggest that these DEPs upon HFD might contribute to memory decline by disturbing neuronal and postsynaptic functions in the hippocampus.

Elevated extracellular matrix protein 1 in circulating extracellular vesicles supports breast cancer progression under obesity conditions

The cargo content in small extracellular vesicles (sEVs) changes under pathological conditions. Our data shows that in obesity, extracellular matrix protein 1 (ECM1) protein levels are significantly increased in circulating sEVs, which is dependent on integrin-β2. Knockdown of integrin-β2 does not affect cellular ECM1 protein levels but significantly reduces ECM1 protein levels in the sEVs released by these cells. In breast cancer (BC), overexpressing ECM1 increases matrix metalloproteinase 3 (MMP3) and S100A/B protein levels. Interestingly, sEVs purified from high-fat diet-induced obesity mice (D-sEVs) deliver more ECM1 protein to BC cells compared to sEVs from control diet-fed mice. Consequently, BC cells secrete more ECM1 protein, which promotes cancer cell invasion and migration. D-sEVs treatment also significantly enhances ECM1-mediated BC metastasis and growth in mouse models, as evidenced by the elevated tumor levels of MMP3 and S100A/B. Our study reveals a mechanism and suggests sEV-based strategies for treating obesity-associated BC.

Solid Dispersions of Genistein via Solvent Rotary Evaporation for Improving Solubility, Bioavailability, and Amelioration Effect in HFD-Induced Obesity Mice.

Genistein (GEN) is an active pharmaceutical ingredient that presents the challenges of poor water solubility and low oral bioavailability. To tackle these challenges, a GEN solid dispersion was prepared by solvent rotary evaporation using polyvinylpyrrolidone K30 (PVP K30) as a carrier. The optimal formulation was determined by drug loading efficiency and in vitro release. The physical state of the solid dispersion was characterized by DSC, XRD, SEM and FT-IR. And the results of the in vitro release study indicate that the drug release of SD (1:7) increased 482-fold that of pure GEN at 60 min. Following oral administration to rats, the Cmax and AUC0-24 of SD (1:7) was increased 6.86- and 2.06-fold to that of pure GEN. The adipose fat index and body weight of the SD (1:7) group were significantly lower than those of the GEN group (p < 0.05). Meanwhile, the levels of TC and TG in the serum were significantly decreased in the SD (1:7) group compared with the GEN group (p < 0.05). All experiments revealed that solid dispersion could be a promising formulation approach to improve the dissolution rate, oral bioavailability, and effect on the reduction of lipid accumulation in high-fat diet-induced obesity mice.

Untargeted metabolomics analysis of probiotic jujube juice and its anti-obesity effects on high-fat-diet-induced obese mice.

Dietary intervention, including polyphenol consumption, is recognized as an effective strategy to prevent obesity. Although fermented jujube juice (FJJ) with lactic acid bacteria has been shown to be rich in polyphenols and have strong antioxidant properties, little is known about its anti-obesity properties. Untargeted metabolomics was employed to identify and analyze the differential metabolites between FJJ and raw jujube juice. A total of 431 metabolites belonging to diverse classes and with various functional active ingredients were quantitatively identified. The animal experiments results showed that FJJ administration for 13 weeks significantly inhibited high-fat-diet-induced body and epididymal adipose weight gain, and improved the serum lipid parameters in obese mice. Additionally, DNA-sequencing results revealed that FJJ treatment increased Akkermansia abundance in the gut and changed the composition of fecal microbiota by decreasing the Firmicutes/Bacteroidota ratio and Helicobacter pylori abundance. These findings suggest that FJJ contributes to regulating lipid accumulation and gut microbiota composition in high-fat-diet-induced obese mice, which helps to prevent obesity. Hence, FJJ has the potential to be a beneficial beverage for controlling obesity. © 2024 Society of Chemical Industry.