High-fat Diet-induced Obesity Research Articles

7769 Natural plant extract alleviates high-fat diet-induced obesity through enhancing PLIN5 expression

Abstract Disclosure: S. Shin: None. H. Jang: None. E. Kwon: None. Obesity is one of the metabolic diseases caused by excessive differentiation and excessive accumulation of adipose tissue due to an imbalance between energy intake and consumption. Various drugs have been developed to effectively treat obesity, but the side effects often outweigh the benefits. Therefore, alternative weight loss supplements that can minimize side effects are needed. In this study, the effects of natural plant extract (NPE) on the high-fat diet (HFD)-induced obesity mice were confirmed to discover new anti-obesity material.After acclimating C57BL/6J mice for 1 week, they were divided into two groups: a normal diet (ND) group and an HFD group. After inducing obesity over 4 weeks, the HFD group was divided into HFD and HFD+NPE and reared together with the ND group for an additional 10 weeks. After a 12-hour fasting period, observations were made on weight, adipose tissue mass, morphological changes in adipocytes, and the expression differences in genes and proteins related to fatty acid oxidation (FAO) in the epididymal white adipose tissue, particularly focusing on the PLIN5 protein.The increase in body weight and epididymal fat mass induced by the HFD was reduced by the administration of NPE. Morphological analysis of the epididymal fat revealed a significant increase in adipocyte size in the HFD group, whereas the NPE group showed a reduction in adipocyte size. The expression of FAO-related genes (PPARa, PGC1a, CPT1, and CPT2) and TCA cycle-related genes (PDHb, ACO, DIST, SUCLG, SDHC, and MDH2) decreased in the epididymal fat due to the HFD, but significantly increased with the administration of NPE. The NPE induced the breakdown of intracellular stored triglycerides by upregulating ATGL, LIPE, and MGL mRNA expression. The resulting liberated fatty acids were translocated to the mitochondria and oxidized through the TCA cycle, ultimately leading to a reduction in body fat. Furthermore, PLIN5 expression exhibited a significantly higher level in the NPE group compared to the other two groups. In other words, elevation in PLIN5 expression, induced by the NPE, appears to enhance lipid breakdown, activate FAO pathways, and stimulate the TCA cycle. Consequently, lipid combustion is increased, improving the weight gain and fat accumulation induced by the HFD.If additional experimental results on human application align with the above findings, NPE holds the potential as a low-side-effect ingredient for weight loss supplements. Presentation: 6/1/2024

Targeting osteoblastic 11β-HSD1 to combat high-fat diet-induced bone loss and obesity

Excessive glucocorticoid (GC) action is linked to various metabolic disorders. Recent findings suggest that disrupting skeletal GC signaling prevents bone loss and alleviates metabolic disorders in high-fat diet (HFD)-fed obese mice, underpinning the neglected contribution of skeletal GC action to obesity and related bone loss. Here, we show that the elevated expression of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), the enzyme driving local GC activation, and GC signaling in osteoblasts, are associated with bone loss and obesity in HFD-fed male mice. Osteoblast-specific 11β-HSD1 knockout male mice exhibit resistance to HFD-induced bone loss and metabolic disorders. Mechanistically, elevated 11β-HSD1 restrains glucose uptake and osteogenic activity in osteoblast. Pharmacologically inhibiting osteoblastic 11β-HSD1 by using bone-targeted 11β-HSD1 inhibitor markedly promotes bone formation, ameliorates glucose handling and mitigated obesity in HFD-fed male mice. Taken together, our study demonstrates that osteoblastic 11β-HSD1 directly contributes to HFD-induced bone loss, glucose handling impairment and obesity.

Alternate-day fasting delays pubertal development in normal-weight mice but prevents high-fat diet-induced obesity and precocious puberty

Background/ObjectivesChildhood obesity, particularly in girls, is linked to early puberty onset, heightening risks for adult-onset diseases. Addressing childhood obesity and precocious puberty is vital to mitigate societal burdens. Despite existing costly and invasive medical interventions, introducing lifestyle-based alternatives is essential. Our study investigates alternate-day fasting’s (ADF) impact on pubertal development in normal-weight and high-fat diet (HFD)-induced obese female mice.MethodsFour groups of female mice were utilized, with dams initially fed control chow during and before pregnancy. Post-parturition, two groups continued on control chow, while two switched to an HFD. Offspring diets mirrored maternal exposure. One control and one HFD group were subjected to ADF. Morphometry and hormone analyses at various time points were performed.ResultsOur findings demonstrate that ADF in normal-weight mice led to reduced body length, weight, uterine, and ovarian weights, accompanied by delayed puberty and lower levels of sex hormones and growth hormone (GH). Remarkably, GH treatment effectively prevented ADF-induced growth reduction but did not prevent delayed puberty. Conversely, an HFD increased body length, induced obesity and precocious puberty, and altered sex hormones and leptin levels, which were counteracted by ADF regimen. Our data indicate ADF’s potential in managing childhood obesity and precocious puberty.ConclusionsADF reduced GH and sex hormone levels, contributing to reduced growth and delayed puberty, respectively. Therefore, parents of normal-weight children should be cautious about prolonged overnight fasting. ADF prevented HFD-induced obesity and precocious puberty, offering an alternative to medical approaches; nevertheless, further studies are needed for translation into clinical practice.

Inulin may prevent the high-fat diet induced-obesity via suppressing endocannabinoid system in the prefrontal cortex in Wistar rats

High-fat diets contribute to various metabolic disorders. Inulin supplementation has been shown to reduce appetite, lower food intake, and promote weight loss. Although there is evidence that the endocannabinoid system has metabolic effects in the prefrontal cortex, studies investigating the effects of inulin on the endocannabinoid system are limited. This study investigated the impact of inulin on obesity through the endocannabinoid system in the prefrontal cortex. Twenty-four male Wistar rats were fed one of four diets over 12 weeks. Findings indicated that a high-fat diet led to obesity, whereas inulin reduced food intake and supported weight loss. Consequently, inulin supplementation both prevented obesity and significantly decreased the expressions of Adrb3 and Adcy1, and anandamide and 2-arachidonylglycerol levels in the prefrontal cortex. Additionally, inulin lowered leptin in circulation and stimulated Trpv1. Thus, inulin may mitigate obesity development, possibly by modulating gene expressions linked to obesity in the prefrontal cortex via endocannabinoids.

Exploring the Effects of Whole Food-Based Dragon Fruit on Metabolic Disorders in High-Fat Diet-Induced Mice.

Metabolic syndrome (MetS) significantly contributes to premature mortality, with obesity being a major risk factor. Dragon fruit, cultivated globally, exhibits bioactivity in preventing obesity-related diseases. Traditional studies using organic solvents for extraction do not align with actual consumption patterns. This study evaluates whole red dragon fruit's effectiveness in ameliorating metabolic disorders using a high-fat diet-induced obesity model in mice for 20 weeks. The experimental groups include the supernatant (RS), precipitate (RP), and pomace (PO) of red dragon fruit juice, compared to the supernatant of white dragon fruit juice (WS). The study finds that dragon fruit extracts reduced adipose tissue weight, body fat percentage, pro-inflammatory cytokines, and improved blood lipid profiles. RP is the most effective, reducing body weight by 4.33g, improving lipid metabolism and glucose homeostasis, and altering gut microbiota to enhance beneficial bacteria and short-chain fatty acids. RP's efficacy in preventing MetS and obesity is attributed to its bioactive components. These findings advocate for using whole fruits in developing functional products, amplifying the agricultural economic value of red dragon fruit.

Luteolin alleviates muscle atrophy, mitochondrial dysfunction and abnormal FNDC5 expression in high fat diet-induced obese rats and palmitic acid-treated C2C12 myotubes

Obesity is associated with a series of skeletal muscle impairments and dysfunctions, which are characterized by metabolic disturbances and muscle atrophy. Luteolin is a phenolic phytochemical with broad pharmacological activities. The present study aimed to evaluate the protective effects of Luteolin on muscle function and explore the potential mechanisms in high-fat diet (HFD)-induced obese rats and palmitic acid (PA)-treated C2C12 myotubes. Male Sprague-Dawley (SD) rats were fed with a control diet or HFD and orally administrated 0.5% sodium carboxymethyl cellulose (vehicle) or Luteolin (25, 50, and 100 mg/kg, respectively) for 12 weeks. The results showed that Luteolin ameliorated HFD-induced body weight gain, glucose intolerance and hyperlipidemia. Luteolin also alleviated muscle atrophy, decreased ectopic lipid deposition and prompted muscle-fiber-type conversion in the skeletal muscle. Meanwhile, we observed an evident improvement in mitochondrial quality control and respiratory capacity, accompanied by reduced oxidative stress. Mechanistic studies indicated that AMPK/SIRT1/PGC-1α signaling pathway plays a key role in the protective effects of Luteolin on skeletal muscle in the obese states, which was further verified by using specific inhibitors of AMPK and SIRT1. Moreover, the mRNA expression levels of markers in brown adipocyte formation were significantly up-regulated post Luteolin supplementation in different adipose depots. Taken together, these results revealed that Luteolin supplementation might be a promising strategy to prevent obesity-induced loss of mass and biological dysfunctions of skeletal muscle.

Diosgenin Alleviates Obesity-Induced Insulin Resistance by Modulating PI3K/Akt Signaling Pathway in Mice Fed a High-Fat Diet.

Obesity is a global medical issue that can be effectively treated by relieving adipose inflammation and subsequent insulin resistance. Diosgenin (DIOS) has various effects as a steroidal saponin in inflammatory disorders. This study explored the effects and mechanism of DIOS on adipose inflammation and insulin sensitivity, both in silico and in vivo. The high-fat diet-induced obesity model in C57BL/6 mice was divided into five groups: normal chow (NC), high-fat diet (HFD), HFD with atorvastatin 10 mg/kg (AT), HFD with DIOS 100 mg/kg (DIOS 100), and HFD with DIOS 200 mg/kg (DIOS 200). Each group underwent an oral intervention for seven weeks. DIOS significantly suppressed weight gain in the body, liver, and epididymal fat pads. Additionally, it significantly improved fasting glucose and insulin levels, homeostatic model assessment of insulin resistance (HOMA-IR), and oral glucose tolerance test results, and reduced the proportion of total and M1 adipose tissue macrophages. Significant changes were shown in mRNA expression of janus kinase 2 (JAK2), insulin receptor (INRS), insulin receptor substrate 1 (IRS-1), phosphatidylinositol 3-kinase (PI3K), and protein kinase B (Akt), all of which exhibited high binding affinity in the in silico. Safety indices, including aspartate aminotransferase (AST), alanine transaminase (ALT), and creatinine level indicated the preventive effects of DIOS. In conclusion, DIOS improves insulin resistance and obesity-associated inflammation via the PI3K/Akt signaling pathway.

Oct-B: A derivative of L-BAIBA significantly alleviating high-fat diet-induced obesity in mice

The rising prevalence of obesity is a global health concern. Supplementation with (S)-β-aminoisobutyric acid (L-BAIBA) has shown potential in preventing obesity and related metabolic disorders induced by high-fat diets. However, developing effective and low-toxicity BAIBA derivatives remains a challenging yet promising field. In this study, we introduce Oct-B, a novel BAIBA ester compound, which exhibits 80-fold greater efficacy than L-BAIBA in alleviating obesity in high-fat diet-fed mice. Our results demonstrate that Oct-B significantly reduces serum TG, TC, LDL-C, and the activities of ALT and AST, and also reduces TG and TC in liver, surpassing the effects of L-BAIBA. Histological analysis shows that Oct-B significantly decreases lipid accumulation in liver tissues, normalizes mast cells in white adipose tissue, and upregulates the expression of UCP1 protein in white adipose tissue. The qRT-PCR results indicated Oct-B alleviates obesity by downregulating lipogenic genes (PPARγ, ACC1, FAS), upregulating lipolysis related genes (PPARα, HSL) and thermogenic gene UCP1. Additionally, quantitative mass spectrometry reveals a marked increase in L-BAIBA levels in white fat, brown fat, serum, and muscle following Oct-B administration. These findings suggest that Oct-B is an efficient L-BAIBA substitute, offering a promising therapeutic approach for preventing and treating high-fat diet-induced obesity.

Serum Extracellular Vesicles Reveal Metabolic Responses to Time-Restricted Feeding in High Fat Diet-Induced Obesity in Male Mice.

Extracellular vesicle (EV) secretion and cargo composition are dysregulated in metabolic diseases. This study aimed to identify changes in the EV size profile and protein cargoes in diet-induced obesity following time-restricted feeding (TRF) and to establish the role of EVs in obesity-related metabolic responses. Mice were fed a high-fat diet (HFD) for 18 weeks prior to being placed either ad libitum or a time-restricted feeding for an additional 10 weeks. Mice on a normal chow ad libitum served as the control. The TRF group had food available for 10 hours and fasted for 14 hours per day. The serum EV size profile and amount displayed sex- and age-dependent changes in HFD-induced obesity, with age reducing EV amounts. HFD decreased small EV populations and increased larger EV populations, while TRF reversed these changes. Quantitative proteomic analysis showed that the abundance and composition of EV proteins changed in response to both acute stimulation with lipopolysaccharides (LPS) and HFD. Gene ontology analysis identified specific sets of EV proteins and their involved biological processes, reflecting the effect of LPS and HFD, as well as the reversal effect of TRF on metabolic and inflammatory pathways. EV proteins altered by HFD and those reversed by TRF had low protein overlap but significant functional overlap in biological processes. TRF activated the PPAR signaling pathway and the AKT-mTOR signaling pathway. The most significant impacts of HFD and TRF were observed on lipoprotein and carbohydrate metabolism, complement system, and neutrophil degranulation. The reversal effect of TRF on the complement system was pathway-specific, significantly activating the lectin complement pathway and restoring neutrophil degranulation. Our data indicate that EVs are involved in diet-induced metabolic and inflammatory responses. Different EV populations may carry distinct sets of proteins involved in specific biological processes, thereby regulating diverse metabolic pathways efficiently.

A natural small molecule pinocembrin resists high-fat diet-induced obesity through GPR120-ERK1/2 pathway

Obesity is a widely concerned health problem. Mobilizing white adipose tissue and reducing fat synthesis are considered as effective strategies in the treatment of obesity. Here, using Connectivity Map (CMap) approach, we identified the pinocembrin (PB), a natural flavonoid primarily found in propolis, as a potential anti-obesity drug. Therefore, high-fat-diet (HFD) mice were randomly divided into two groups and fed a HFD or HFD with PB in this study. In vivo experiments showed that supplementation of PB reduced the body weight gain and ameliorated insulin resistance in HFD-induced mice. More importantly, PB did not cause side effect through detecting the levels of alanine transaminase (ALT), aspartate aminotransferase (AST), creatinine (CRE) and blood urea nitrogen (BUN) in serum of mice. Additionally, PB reduced expansion of white adipose tissue with upregulation of genes related lipolysis and downregulation of genes related lipogenesis. Furthermore, in vitro experiments revealed that PB treatment dose-dependently inhibited lipid droplet formation with upregulation of genes related lipolysis and downregulation of genes related lipogenesis. Molecular docking analysis combined with cellular thermal shift assay (CETSA) suggested that PB has a high affinity to the G protein-coupled receptor 120 (GPR120). Meanwhile, we confirmed that PB efficiently inhibited adipogenic differentiation of preadipocytes by directly binding to GPR120 and subsequently activating the downstream phosphorylation extracellular regulated kinase 1/2 (ERK1/2). Collectively, PB exerted anti-obesity effect through GPR120-ERK1/2 signaling pathway, providing a novel and promising natural drug for the treatment of obesity.

Protective effects of menthol against olanzapine-induced metabolic alterations in female mice

AimMetabolic comorbidities such as obesity type 2 diabetes, insulin resistance, glucose intolerance, dyslipidemia are the major contributors for lower life expectancy and reduced patient compliance during antipsychotic therapy in patients with severe mental illnesses such as schizophrenia, bipolar disorder, and depression. TRPM8 activation by menthol is also reported to alleviate high fat diet-induced obesity in mice. Additionally, this TRPM8 activation leads to increase in gene expression of thermogenic genes in white adipocytes and dietary menthol was found to increase browning of WAT along with improved glucose utilization. Therefore, we aimed to evaluate the plausible role of TRPM8 channels in olanzapine-induced metabolic alterations in female balb/c mice. Methods6 weeks olanzapine (6 mg kg−1, per oral) model was used in female balb/c mice. Pharmacological manipulation of TRPM8 channel was done using menthol and N-(3-aminopropyl)-2-[(3-methylphenyl)methoxy]-N-(2-thienylmethyl)-benzamide (AMTB), the agonist and antagonist respectively. Key resultsMenthol co-treatment for six weeks prevented olanzapine-induced metabolic alterations such as weight gain, increased food intake, decreased energy expenditure, adiposity, liver lipid accumulation, systemic inflammation and insulin resistance. Although no significant change in TRPM8 mRNA expression was found in the hypothalamus, however, some of the protective effects of menthol were absent in presence of AMTB indicating possible involvement of TRPM8 channels. ConclusionOur results suggest possible therapeutic implications of menthol in the management of antipsychotic-induced weight gain and other metabolic alterations.

Therapeutic effects of alpha lipoic acid and/or caffeine-loaded chitosan nanoparticles on memory impairment and neurochemical changes in high-fat diet-induced obese rats

The therapeutic effects of alpha lipoic acid (LA) and/or caffeine-loaded chitosan nanoparticles (CCNPs) on obesity-induced memory impairment were evaluated in the present study. Rats were divided into control rats, obese rats induced by high fat diet (HFD) and obese rats treated with LA and/or CCNPs. Obesity was confirmed by measuring the body mass index (BMI). Memory and cognitive functions were evaluated by novel object recognition test (NORT). The levels of serotonin (5-HT), dopamine (DA), norepinephrine (NE), lipid peroxidation (MDA), nitric oxide (NO), reduced glutathione (GSH), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), leptin (LEP) and ghrelin (GHR) and the activities of monoamine oxidase (MAO), acetylcholinesterase (AchE) and Na+,K+,ATPase were determined in the cortex and hippocampus. The cerebral histopathological alterations were examined in obese rats.Obese rats showed impaired memory and exhibited significant neurochemical changes, including decreased levels of 5-HT, DA, GSH, GHR, and Na+,K+-ATPase activity, as well as an increase in AchE, MAO, MDA, NO, IL-1β, TNF-α, and LEP. LA and/or CCNPs treatment reduced BMI and improved memory. LA or CCNPs alleviated the cortical and hippocampal neurochemical changes and histopathological changes induced by obesity. Furthermore, LA and CCNPs exhibited antioxidant and anti-inflammatory properties, which likely contributed to their effects. However, no synergistic effect was observed between LA and CCNPs. These findings suggest that LA or CCNPs may be a potential therapy against obesity and its adverse effects on memory, mediated by their ability to restore monoamine levels and exhibit antioxidant and anti-inflammatory properties.

Branched-chain amino acids supplementation induces insulin resistance and pro-inflammatory macrophage polarization via INFGR1/JAK1/STAT1 signal pathway

BackgroundObesity is a global epidemic, and the low-grade chronic inflammation of adipose tissue in obese individuals can lead to insulin resistance and type 2 diabetes. Adipose tissue macrophages (ATMs) are the main source of pro-inflammatory cytokines in adipose tissue, making them an important target for therapy. While branched-chain amino acids (BCAA) have been strongly linked to obesity and type 2 diabetes in humans, the relationship between BCAA catabolism and adipose tissue inflammation is unclear. This study aims to investigate whether disrupted BCAA catabolism influences the function of adipose tissue macrophages and the secretion of pro-inflammatory cytokines in adipose tissue, and to determine the underlying mechanism. This research will help us better understand the role of BCAA catabolism in adipose tissue inflammation, obesity, and type 2 diabetes.MethodsIn vivo, we examined whether the BCAA catabolism in ATMs was altered in high-fat diet-induced obesity mice, and if BCAA supplementation would influence obesity, glucose tolerance, insulin sensitivity, adipose tissue inflammation and ATMs polarization in mice. In vitro, we isolated ATMs from standard chow and high BCAA-fed group mice, using RNA-sequencing to investigate the potential molecular pathway regulated by BCAA accumulation. Finally, we performed targeted gene silence experiment and used immunoblotting assays to verify our findings.ResultsWe found that BCAA catabolic enzymes in ATMs were influenced by high-fat diet induced obesity mice, which caused the accumulation of both BCAA and its downstream BCKA. BCAA supplementation will cause obesity and insulin resistance compared to standard chow (STC) group. And high BCAA diet will induce pro-inflammatory cytokines including Interlukin-1beta (IL-1β), Tumor Necrosis Factor alpha (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) secretion in adipose tissue as well as promoting ATMs M1 polarization (pro-inflammatory phenotype). Transcriptomic analysis revealed that a high BCAA diet would activate IFNGR1/JAK1/STAT1 pathway, and IFNGR1 specific silence can abolish the effect of BCAA supplementation-induced inflammation and ATMs M1 polarization.ConclusionsThe obesity mice model reveals the catabolism of BCAA was disrupted which will cause the accumulation of BCAA, and high-level BCAA will promote ATMs M1 polarization and increase the pro-inflammatory cytokines in adipose tissue which will cause the insulin resistance in further. Therefore, reducing the circulating level of BCAA can be a therapeutic strategy in obesity and insulin resistance patients.

Obesity Prevention Effects of Avocado (Persea americana) Seed Powder in High-Fat Diet-Induced Obesity in Rats

Avocado seed contains 64% of the phenolic compounds of the whole fruit. This makes avocado seed a potential candidate for the development of treatments for different illnesses, including obesity (the major risk factor for metabolic disorders). The aim of this study was to investigate the effects of avocado seed powder on high-fat diet-induced obesity in rats. Sprague Dawley rats (16 rats) were fed a high-fat diet for 10 weeks. After 10 weeks, the rats were assigned into two groups of eight animals each and were fed either a high-fat diet (HFD; control group) or a high-fat diet containing avocado seed powder (HFD-A; treatment group) for 6 weeks. Animals were weighed weekly, and weekly weight gain was determined. Animals in the treatment (avocado seed) group showed significantly lower body weight gain (7.8 ± 9.63 g) than animals in the control group (33.9 ± 10.84 g) at the end of this study. The treatment group presented with lower triglycerides than the control, with LDL and HDL comparable to the control group. Avocado seed powder showed potential to reduce obesity in rats fed a high-fat diet. Avocado seed can therefore be investigated further as a potential anti-obesity nutraceutical.

Human milk oligosaccharide 2’-fucosyllactose protects against high-fat diet-induced obesity by changing intestinal mucus production, composition and degradation linked to changes in gut microbiota and faecal proteome profiles in mice

ObjectiveTo decipher the mechanisms by which the major human milk oligosaccharide (HMO), 2’-fucosyllactose (2’FL), can affect body weight and fat mass gain on high-fat diet (HFD) feeding in mice. We...

Edible Vitalmelon Fruit Extract Promotes Lipolysis of MDI-stimulated 3T3-L1 Adipocytes Through the Stimulation of Glycerol Release and β-oxidation

Background and Purpose: The anti-obesity effects of vitalmelon extracts have been well verified in only adipogenesis and lipogenesis of adipocytes and high-fat diet-induced obesity mice except lipolysis. Therefore, we were investigated the novel function of edible vitalmelon fruit water extract (VW) on lipolysis. Methods: The changes in the free glycerol release, cyclic adenosine monophosphate (cAMP)-dependent signaling pathway, and expression of β-oxidation-related regulators were analyzed in 3‐isobutyl‐1‐methylxanthine, dexamethasone, and insulin (MDI)-stimulated 3T3‐L1 adipocytes (MiSt-3T3 adipocytes) after a VW treatment. Results: The successful differentiation of pre-adipocytes was confirmed with increased oil-red O (ORO)-stained lipid accumulation and PPARγ gene transcription. After maturation of adipocytes, the levels of free glycerol, intracellular cAMP, and hormone-sensitive lipase phosphorylation increased in a dose-dependent manner in the MDI+VW-treated group. In addition, the protein and mRNA levels of three β-oxidation-related genes (ACADs, ACO1, and CTP) were remarkably increased in the MiSt-3T3 adipocytes after VW treatment, while ATPCL phosphorylation was decreased. The changes in the expression levels of these proteins were accompanied by alteration on the expression levels of the PPARα transcription factors. The levels of PPARα protein phosphorylation and mRNA transcription in MiSt-3T3 adipocytes increased dose-dependently after the VW treatment. Conclusion: These results show that VW can promote lipolysis by controlling the cAMP-mediated glycerol release pathway and β-oxidation in MiSt-3T3 adipocytes.

Exploring molecular mechanisms of exercise on metabolic syndrome: a bibliometric and visualization study using CiteSpace.

To investigate the molecular mechanisms through which exercise influences metabolic syndrome (MS) and identify key research trends and collaborative networks using bibliometric and visualization techniques. We conducted a systematic literature search using the Web of Science Core Collection for articles published from 2014 to 2023. Using CiteSpace, we performed a bibliometric analysis of 562 eligible papers, generating visual knowledge maps to identify prevailing patterns, popular subjects, and emerging trends in the literature. The study reveals that exercise mitigates MS by reversing high-fat diet-induced abdominal obesity, reducing lipid accumulation and inflammation, enhancing insulin sensitivity, and improving cardiovascular function. Key molecular pathways include PPAR-γ/CPT-1/MCAD signaling, AMPK activation, and nitric oxide production. The USA leads in research output, with significant contributions from American institutions. Collaboration among researchers is limited, highlighting the need for more extensive and high-quality research initiatives. Regular, moderate-to-high-intensity exercise is crucial for managing MS. Exercise activates beneficial molecular pathways, improving metabolic health and cardiovascular function. Future research should focus on expanding collaborations and exploring novel molecular targets to enhance the therapeutic potential of exercise in metabolic syndrome management.

LP-54 Protective effect of aryl hydrocarbon receptor (AHR) against high-fat diet-induced obesity in female mice

LP-54 Protective effect of aryl hydrocarbon receptor (AHR) against high-fat diet-induced obesity in female mice

Long-Term Exposure to Polystyrene Microspheres and High-Fat Diet-Induced Obesity in Mice: Evaluating a Role for Microbiota Dysbiosis.

Microplastics (MPs) have become a global environmental problem, emerging as contaminants with potentially alarming consequences. However, long-term exposure to polystyrene microspheres (PS-MS) and its effects on diet-induced obesity are not yet fully understood. We aimed to investigate the effect of PS-MS exposure on high-fat diet (HFD)-induced obesity and underlying mechanisms. In the present study, C57BL/6J mice were fed a normal diet (ND) or a HFD in the absence or presence of PS-MS via oral administration for 8 wk. Antibiotic depletion of the microbiota and fecal microbiota transplantation (FMT) were performed to assess the influence of PS-MS on intestinal microbial ecology. We performed 16S rRNA sequencing to dissect microbial discrepancies and investigated the dysbiosis-associated intestinal integrity and inflammation in serum. Compared with HFD mice, mice fed the HFD with PS-MS exhibited higher body weight, liver weight, metabolic dysfunction-associated steatotic liver disease (MASLD) activity scores, and mass of white adipose tissue, as well as higher blood glucose and serum lipid concentrations. Furthermore, 16S rRNA sequencing of the fecal microbiota revealed that mice fed the HFD with PS-MS had greater -diversity and greater relative abundances of Lachnospiraceae, Oscillospiraceae, Bacteroidaceae, Akkermansiaceae, Marinifilaceae, Deferribacteres, and Desulfovibrio, but lower relative abundances of Atopobiaceae, Bifidobacterium, and Parabacteroides. Mice fed the HFD with PS-MS exhibited lower expression of MUC2 mucin and higher levels of lipopolysaccharide and inflammatory cytokines [tumor necrosis factor- (TNF-), interleukin-6 (IL-6), IL-1, and IL-17A] in serum. Correlation analyses revealed that differences in the microbial flora of mice exposed to PS-MS were associated with obesity. Interestingly, microbiota-depleted mice did not show the same PS-MS-associated differences in Muc2 and Tjp1 expression in the distal colon, expression of inflammatory cytokines in serum, or obesity outcomes between HFD and HFD + PS-MS. Importantly, transplantation of feces from HFD + PS-MS mice to microbiota-depleted HFD-fed mice resulted in a lower expression of mucus proteins, higher expression of inflammatory cytokines, and obesity outcomes, similar to the findings in HFD + PS-MS mice. Our findings provide a new gut microbiota-driven mechanism for PS-MS-induced obesity in HFD-fed mice, suggesting the need to reevaluate the adverse health effects of MPs commonly found in daily life, particularly in susceptible populations. https://doi.org/10.1289/EHP13913.

Eriodictyol regulates white adipose tissue browning and hepatic lipid metabolism in high fat diet-induced obesity mice via activating AMPK/SIRT1 pathway

Ethnopharmacological relevanceBlossom of Citrus aurantium L. var. amara Engl. (CAVA) has been popularly consumed as folk medicine and dietary supplement owing to its various beneficial effects and especially anti-obesity potential. Our previous study predicted that eriodictyol was probably one of the key active compounds of the total flavonoids from blossom of CAVA. However, effects of eriodictyol in anti-obesity were still elusive. Aim of the studyThis study was performed to explore the precise role of eriodictyol in white adipose tissue (WAT) browning and hepatic lipid metabolism, and simultaneously, to verify the impact of eriodictyol on the total flavonoids of CAVA in losing weight. Materials and methodsThe pancreas lipase assay was conducted and oleic acid-induced HepG2 cells were established to preliminarily detect the lipid-lowering potential of eriodictyol. Then, high fat diet-induced obesity (DIO) mouse model was established for in vivo studies. The biochemical indicators of mice were tested by commercial kits. The histopathological changes of WAT and liver in mice were tested by H&E staining, Oil Red O staining and Sirius Red staining. Immunohistochemical, Western blot assay, as well as RT-qPCR analysis were further performed. Additionally, molecular docking assay was used to simulate the binding of eriodictyol with potential target proteins. ResultsIn vitro studies showed that eriodictyol intervention potently inhibited pancreatic lipase activity and reversed hepatic steatosis in oleic acid-induced HepG2 cells. Consistently, long-term medication of eriodictyol also effectively prevented obesity and improved lipid and glucose metabolism in diet-induced obesity mice. Obesity-induced histopathological changes in iWAT, eWAT and BAT, and abnormal expression levels of IL-10, IL-6 and TNF-α in iWAT of DIO mice were also significantly reversed by eriodictyol treatment. Eriodictyol administration significantly and potently promoted browning of iWAT by increasing expression levels of thermogenic marker protein of UCP1, as well as brown adipocyte-specific genes of PGC-1α, SIRT1 and AMPKα1. Further assays revealed that eriodictyol enhanced mitochondrial function, as shown by an increase in compound IV activity and the expression of tricarboxylic acid cycle-related genes. Besides, eriodictyol addition markedly reversed hepatic damages and hepatic inflammation, and enhanced hepatic lipid metabolism in DIO mice, as evidenced by its regulation on p-ACC, CPT1-α, UCP1, PPARα, PGC-1α, SIRT1 and p-AMPKα expression. Molecular docking results further validated that AMPK/SIRT1 pathway was probably the underlying mechanisms by which eriodictyol acted. ConclusionEriodictyol exhibited significant anti-obesity effect, which was comparable to that of the total flavonoids from blossom of CAVA. These findings furnished theoretical basis for the application of eriodictyol in weight loss.