Flavopiridol inhibits adipogenesis and improves metabolic homeostasis by ameliorating adipose tissue inflammation in a diet-induced obesity model.

Repositioning of FDA approved/clinical phase drugs has recently opened a new opportunity for rapid approval of drugs, as it shortens the overall process of drug discovery and development. In previous studies, we predicted the possibility of better activity profiles of flavopiridol, the FDA approved orphan drug with better fit value 2.79 using a common feature pharmacophore model for anti-adipogenic compounds (CFMPA). The present study aimed to investigate the effect of flavopiridol on adipocyte differentiation and to determine the underlying mechanism. Flavopiridol inhibited adipocyte differentiation in different cell models like 3T3-L1, C3H10T1/2, and hMSCs at 150 nM. Flavopiridol was around 135 times more potent than its parent molecule rohitukine. The effect was mediated through down-regulation of key transcription factors of adipogenesis i.e. Peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα), and their downstream targets, including adipocyte protein -2 (aP2) and fatty acid synthase (FAS). Further, results revealed that flavopiridol arrested the cell cycle in G1/S phase during mitotic clonal expansion by suppressing cell cycle regulatory proteins i.e. Cyclins and CDKs. Flavopiridol inhibited insulin-stimulated signalling in the early phase of adipocyte differentiation by downregulation of AKT/mTOR pathway. In addition, flavopiridol improved mitochondrial function in terms of increased oxygen consumption rate (OCR) in mature adipocytes. In the mouse model of diet-induced obesity, flavopiridol attenuated obesity-associated adipose tissue inflammation and improved serum lipid profile, glucose tolerance as well as insulin sensitivity. In conclusion, the FDA approved drug flavopiridol could be placed as a potential drug candidate for the treatment of cancer and obesity comorbid patients.

Lycium chinense Mill Induces Anti-Obesity and Anti-Diabetic Effects In Vitro and In Vivo.

This study investigated the effects of Lycium chinense Mill (LCM) extract on obesity and diabetes, using both in vitro and high-fat diet (HFD)-induced obesity mouse models. We found that LCM notably enhanced glucagon-like peptide-1 (GLP-1) secretion in NCI-h716 cells from 411.4 ± 10.75 pg/mL to 411.4 ± 10.75 pg/mL compared to NT (78.0 ± 0.67 pg/mL) without causing cytotoxicity, implying the involvement of Protein Kinase A C (PKA C) and AMP-activated protein kinase (AMPK) in its action mechanism. LCM also decreased lipid droplets and lowered the expression of adipogenic and lipogenic indicators, such as Fatty Acid Synthase (FAS), Fatty Acid-Binding Protein 4 (FABP4), and Sterol Regulatory Element-Binding Protein 1c (SREBP1c), indicating the suppression of adipocyte differentiation and lipid accumulation. LCM administration to HFD mice resulted in significant weight loss (41.5 ± 3.3 g) compared to the HFD group (45.1 ± 1.8 g). In addition, improved glucose tolerance and serum lipid profiles demonstrated the ability to counteract obesity-related metabolic issues. Additionally, LCM exhibited hepatoprotective properties by reducing hepatic lipid accumulation and diminishing white adipose tissue mass and adipocyte size, thereby demonstrating its effectiveness against hepatic steatosis and adipocyte hypertrophy. These findings show that LCM can be efficiently used as a natural material to treat obesity and diabetes, providing a new approach for remedial and therapeutic purposes.

Capsaicin Reduces Obesity by Reducing Chronic Low-Grade Inflammation.

Chronic low-grade inflammation (CLGI) is associated with obesity and is one of its pathogenetic mechanisms. Lipopolysaccharide (LPS), a component of Gram-negative bacterial cell walls, is the principal cause of CLGI. Studies have found that capsaicin significantly reduces the relative abundance of LPS-producing bacteria. In the present study, TRPV1-knockout (TRPV1-/-) C57BL/6J mice and the intestinal epithelial cell line Caco-2 (TRPV1-/-) were used as models to determine the effect of capsaicin on CLGI and elucidate the mechanism by which it mediates weight loss in vivo and in vitro. We found that the intragastric administration of capsaicin significantly blunted increases in body weight, food intake, blood lipid, and blood glucose in TRPV1-/- mice fed a high-fat diet, suggesting an anti-obesity effect of capsaicin. Capsaicin reduced LPS levels in the intestine by reducing the relative abundance of Proteobacteria such as Helicobacter, Desulfovibrio, and Sutterella. Toll-like receptor 4 (TLR4) levels decreased following decreases in LPS levels. Then, the local inflammation of the intestine was reduced by reducing the expression of tumor necrosis factor (TNF)-α and interleukin (IL)-6 mediated by TLR4. Attenuating local intestinal inflammation led to the increased expression of tight junction proteins zonula occludens 1 (ZO-1) and occludin and the restoration of the intestinal barrier function. Capsaicin increased the expression of ZO-1 and occludin at the transcriptional and translational levels, thereby increasing trans-endothelial electrical resistance and restoring intestinal barrier function. The restoration of intestinal barrier function decreases intestinal permeability, which reduces the concentration of LPS entering the circulation, and reduced endotoxemia leads to decreased serum concentrations of inflammatory cytokines such as TNF-α and IL-6, thereby attenuating CLGI. This study sheds light on the anti-obesity effect of capsaicin and its mechanism by reducing CLGI, increasing our understanding of the anti-obesity effects of capsaicin. It has been confirmed that capsaicin can stimulate the expression of intestinal transmembrane protein ZO-1 and cytoplasmic protein occludin, increase the trans-epithelial electrical resistance value, and repair intestinal barrier function.

Drosophila models of the anti-inflammatory and anti-obesity mechanisms of kombucha tea produced by Camellia sinensis leaf fermentation.

Kombucha tea is a traditional beverage originating from China and has recently gained popularity worldwide. Kombucha tea is produced by the fermentation of tea leaves and is characterized by its beneficial properties and varied chemical content produced during the fermentation process, which includes organic acids, amino acids, vitamins, minerals, and other biologically active compounds. Kombucha tea is often consumed as a health drink to combat obesity and inflammation; however, the bioactive effects of kombucha tea have not been thoroughly researched. In this study, we reveal the underlying mechanisms of the beneficial properties of kombucha tea and how they protect against obesity and inflammation by studying Drosophila models. We established an inflammatory Drosophila model by knocking down the lipid storage droplet-1 gene, a human perilipin-1 ortholog. In this model, dysfunction of lipid storage droplet-1 induces inflammation by enhancing the infiltration of hemocytes into adipose tissues, increasing reactive oxygen species production, elevating levels of proinflammatory cytokines, and promoting the differentiation of hemocytes into macrophages. These processes are regulated by the c-Jun N-terminal Kinase (JNK) pathway. Using this unique Drosophila model that mimics mammalian inflammation, we verified the beneficial effects of kombucha tea on reducing tissue inflammation. Our data confirms that kombucha tea effectively improves inflammatory conditions by suppressing the expression of cytokines and proinflammatory responses induced by lipid storage droplet-1 dysfunction. It was found that kombucha tea consumption alleviated the production of reactive oxygen species and activated the JNK signaling pathway, signifying its potential as an anti-inflammatory agent against systemic inflammatory responses connected to the JNK pathway. Kombucha tea reduced triglyceride accumulation by increasing the activity of Brummer (a lipase), thereby promoting lipolysis in third-instar larvae. Therefore, kombucha tea could be developed as a novel, functional beverage to protect against obesity and inflammation. Our study also highlights the potential use of this innovative model to evaluate the effects of bioactive compounds derived from natural products.

Potential barriers to the use of anti-obesity medications in persons with spinal cord injuries and disorders.

Background: Anti-obesity medications (AOMs) may provide a viable option for obesity management. However, little is known about the use of AOMs in persons with SCI/D. Objective: Describe health care providers' (HCPs) views about barriers to AOM use in persons living with SCI/D. Methods: Descriptive qualitative design using in-depth interviews Descriptive statistics were used to calculate demographic and employment characteristics. Interviews were audio-recorded and transcribed verbatim. Transcripts were coded and analyzed using Braun and Clarke's (2006) six thematic analysis phases. Results: HCPs (n = 12) were from 11 different nationwide facilities. Most HCPs were male (75%), a large majority were white (67%), and most were 26-49 years of age. Participants were dietitians (75%), physicians (17%), and psychologists (8%). HCPs ranged from 1.5 to 15 years of providing SCI/D care. HCPs described four main thematic barriers to AOM use in persons with SCI/D: (1) AOM side effects that are especially concerning in persons with SCI/D; (2) AOMs contribute to poor eating habits; (3) availability, accessibility, and administration; and (4) lack of evidence, clinical agreement, and knowledge about AOM use in the SCI/D population. Conclusions: There are several potential barriers to AOM use in the SCI/D population. Barriers include AOM side effects which may cause or exacerbate conditions that are already concerns in persons with SCI/D, such as bowel and skin problems, and muscle loss. SCI/D HCPs reported a lack of evidence about AOM use in persons with SCI/D, but interest in obtaining more knowledge.

Anti-obesity Drugs for the Treatment of Binge Eating Disorder: Opportunities and Challenges.

Binge eating disorder (BED) is the most prevalent form of disordered eating, frequently associated with obesity. Both these conditions along with sharing overeating behaviour features can lead to substantial burden of disease and premature mortality. With limited specific evidence available on pharmacotherapy, since lisdexamfetamine is approved only in some countries, new drugs are urgently needed to provide physicians with efficacious prescribing choices when treating BED. Although unique mechanisms underlie psychopathological features of binge eating, including impulsivity, compulsivity, and emotional reactivity, anti-obesity drugs might represent an option for both weight management and symptom reduction in people with BED. The aim of this review is thus to provide a summary of available evidence on the efficacy of anti-obesity drugs for BED. After comprehensively searching for relevant studies in PubMed and the Cochrane Library, as well as for unpublished results in ClinicalTrials.gov, we included 14 clinical trials. Despite the limited sample size and the methodological variability, evidence from available studies suggests that most anti-obesity drugs, namely phentermine/topiramate, naltrexone/bupropion, liraglutide and semaglutide, though not orlistat, might variously achieve improvements for both body weight and severity and frequency of binge episodes. Findings from ongoing clinical trials are likely to provide further insight into the possible role of anti-obesity drugs for treating BED. Since these agents can hold the potential to be misused potentiating dietary restriction and pathological weight loss, it is crucial to promote responsible prescribing practices.

Isolation, characterization, and LC MS/MS determination of anti-obesity components from pine needles of Cedrus deodara (Roxb.) G. Don.

Objective: This study aimed to isolate and analyze the components in cedar pine needles (needle leaves of Cedrus deodara (Roxb.) G. Don) that exhibit anti-obesity effects, as determined through animal experiments. Methods: The extract of cedar pine needles was separated into four fractions of different polarities using a macroporous resin column. The fraction that retained anti-obesity activity was evaluated based on the results of animal experiments. Monomeric compounds were structurally characterized and isolated from the active fraction using a preparative liquid chromatography system. Combined with subsequent glucose gel chromatographic separation. The content of the separated components was determined using ultrahigh performance liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC-QQQ-MS/MS). Results: The water-washed fraction retained anti-obesity activity of the cedar pine needles more effectively. A total of 16 compounds were separated from this fraction, and the contents of 14 of these compounds were determined to be present in cedar pine needles. Conclusion: Nine components, namely p-hydroxy benzyl alcohol, chlorogenic acid, vanillic acid, syringic acid, P-coumaric acid, sinapic acid, benzoic acid, phenylacetic acid, salicylic acid, were characterized and determined for the first time in cedar pine needles. The components with anti-obesity activity in the pine needles of Cedrus are mainly derived from phenolic acids.

Design, synthesis and structure-activity relationship of novel 2-pyrimidinylindole derivatives as orally available anti-obesity agents.

Due to the emerging global epidemic of obesity, developing safe and effective agents for anti-obesity is urgently needed. Our previous study found that 2-pyrimidinylindole derivative Wd3d exhibited potential anti-obesity activity. Herein, to further optimize the potential moiety, structural modifications were proceeded for two rounds in this study. Firstly, we designed, synthesized, and evaluated 36 new derivatives of 2-pyrimidinylindole scaffold with different substituents on the indole ring and pyrimidine ring to investigate their structure-activity relationship (SAR). Then, analogs with potent activity had the aldehyde group replaced with the acylhydrazone group to reduce cytotoxicity and improve metabolic stability. Detailed SAR studies and animal evaluation experiments led to the discovery of the compound 9ga, which significantly reduced TG accumulation with an EC50 value of 0.07 µM and showed relatively low cytotoxicity with an IC50 value of around 24 µM. Oral administration of 9ga effectively prevented the excessive growth of body weight and lessened fat mass as well as liver mass, decreased lipid accumulation in the liver and blood, and improved the heart injury parameter in the diet-induced obesity mouse model significantly better than Wd3d. A mechanism study showed that 9ga regulated the lipid metabolism during early adipogenesis by inhibiting PPARγ pathway. In conclusion, our study further highlights the anti-obesity potential of 2-pyrimidinylindole derivatives in diet-induced obesity.

Nicotinamide N-methyltransferase inhibition mitigates obesity-related metabolic dysfunction.

AIM: To assess the effects of a small-molecule nicotinamide N-methyltransferase (NNMT) inhibitor, 5A1MQ, on body composition, metabolic variables, fatty liver pathologies, and circulating biomarkers in diet-induced obese (DIO) mice, and characterize its plasma pharmacokinetics (PK) and tissue distribution in vivo. MATERIALS AND METHODS: DIO mice were administered vehicle or 5A1MQ once daily for 28 days. Longitudinal measures of body composition, blood glucose and plasma insulin levels, and terminal measures of liver histopathology and serum markers, were evaluated. Plasma and tissue PK were established in age- and strain-matched mice after intravenous, oral, and subcutaneous dosing of 5A1MQ. RESULTS: 5A1MQ treatment dose-dependently limited body weight and fat mass gains, improved oral glucose tolerance and insulin sensitivity, and suppressed hyperinsulinaemia in DIO mice. Liver histology from 5A1MQ-treated DIO mice showed attenuated hepatic steatosis and macrophage infiltration, and correspondingly reduced liver weight, size, and triglyceride levels. 5A1MQ treatment normalized circulating levels of alanine transaminase, aspartate transaminase, and ketone bodies, supporting an overall improvement in liver and metabolic functions. The pharmacodynamic effects of 5A1MQ were further corroborated by its high systemic exposure and effective distribution to metabolically active tissues, including adipose, muscle and liver, following subcutaneous dosing of mice. CONCLUSIONS: This work validates NNMT inhibition as a viable pharmacological approach to ameliorate metabolic imbalances and improve liver pathologies that develop with obesity.

Inhibitory Activity of Sparassis latifolia on the Lipid Accumulation through Suppressing Adipogenesis and Activating Lipolysis in 3T3-L1 Cells.

Sparassis latifolia (SL) has been reported to exhibit anti-obesity effects in high-fat diet animal models, yet research into its mechanisms of action remains limited. Therefore, this study aimed to elucidate the mechanisms behind the anti-obesity activity of SL's 30% ethanol extract (SL30E) using 3T3-L1 cells in an in vitro setting. SL30E effectively mitigated the accumulation of lipid droplets and triacylglycerol. SL30E downregulated PPARγ and CEBPα protein levels. The diminishment of PPARγ and C/EBPα, facilitated by SL30E, was impeded by the knockdown of ß-catenin using ß-cateninspecific siRNA. Furthermore, SL30E was observed to increase the protein levels of ATGL and p-HSL, while it concurrently decreased the protein levels of perilipin-1. SL30E downregulated p62/SQSTM1 protein level and upregulated LC3-II protein level. Moreover, SL30E was demonstrated to elevate the protein levels of p-AMPK and PGC-1α. The results indicate that SL30E inhibits lipid accumulation by suppressing adipogenesis and inducing lipolysis, lipophagy, and thermogenesis in 3T3-L1 cells. These observations provide potential insights into the mechanisms underlying the anti-obesity effects of SL, contributing valuable information to the existing body of knowledge.

Obesity and cardiovascular disease: an ESC clinical consensus statement.

The global prevalence of obesity has more than doubled over the past four decades, currently affecting more than a billion individuals. Beyond its recognition as a high-risk condition that is causally linked to many chronic illnesses, obesity has been declared a disease per se that results in impaired quality of life and reduced life expectancy. Notably, two-thirds of obesity-related excess mortality is attributable to cardiovascular disease. Despite the increasingly appreciated link between obesity and a broad range of cardiovascular disease manifestations including atherosclerotic disease, heart failure, thromboembolic disease, arrhythmias, and sudden cardiac death, obesity has been underrecognized and sub-optimally addressed compared with other modifiable cardiovascular risk factors. In the view of major repercussions of the obesity epidemic on public health, attention has focused on population-based and personalized approaches to prevent excess weight gain and maintain a healthy body weight from early childhood and throughout adult life, as well as on comprehensive weight loss interventions for persons with established obesity. This clinical consensus statement by the European Society of Cardiology discusses current evidence on the epidemiology and aetiology of obesity; the interplay between obesity, cardiovascular risk factors and cardiac conditions; the clinical management of patients with cardiac disease and obesity; and weight loss strategies including lifestyle changes, interventional procedures, and anti-obesity medications with particular focus on their impact on cardiometabolic risk and cardiac outcomes. The document aims to raise awareness on obesity as a major risk factor and provide guidance for implementing evidence-based practices for its prevention and optimal management within the context of primary and secondary cardiovascular disease prevention.

Obesity and cardiovascular disease: an ESC clinical consensus statement.

The global prevalence of obesity has more than doubled over the past four decades, currently affecting more than a billion individuals. Beyond its recognition as a high-risk condition that is causally linked to many chronic illnesses, obesity has been declared a disease per se that results in impaired quality of life and reduced life expectancy. Notably, two-thirds of obesity-related excess mortality is attributable to cardiovascular disease. Despite the increasingly appreciated link between obesity and a broad range of cardiovascular disease manifestations including atherosclerotic disease, heart failure, thromboembolic disease, arrhythmias, and sudden cardiac death, obesity has been underrecognized and sub-optimally addressed compared with other modifiable cardiovascular risk factors. In the view of major repercussions of the obesity epidemic on public health, attention has focused on population-based and personalized approaches to prevent excess weight gain and maintain a healthy body weight from early childhood and throughout adult life, as well as on comprehensive weight loss interventions for persons with established obesity. This clinical consensus statement by the European Society of Cardiology discusses current evidence on the epidemiology and aetiology of obesity; the interplay between obesity, cardiovascular risk factors and cardiac conditions; the clinical management of patients with cardiac disease and obesity; and weight loss strategies including lifestyle changes, interventional procedures, and anti-obesity medications with particular focus on their impact on cardiometabolic risk and cardiac outcomes. The document aims to raise awareness on obesity as a major risk factor and provide guidance for implementing evidence-based practices for its prevention and optimal management within the context of primary and secondary cardiovascular disease prevention.

The impact of approved anti-obesity medications on osteoarthritis.

BACKGROUND: Obesity has been established as a significant risk factor for osteoarthritis. Anti-obesity medications (AOMs) have demonstrated efficacy in weight management. However, potential impact on osteoarthritis risk remains uncertain. METHODS: This retrospective cohort study used Kythera data from NOV2022 to JULY2024. Patients with obesity using AOMs were identified through diagnosis and prescription claims for tirzepatide, semaglutide, or liraglutide between 1NOV2023 and 31JAN2024, with a 6-month follow-up to assess OA risk. OA risk, analyzed using Cox regression and propensity score matching, controlled for comorbidities and sociodemographic factors. RESULTS: There were 39,394 patients living with obesity using AOM (23,933 semaglutide 12,854 tirzepatide, 2,607 liraglutide) and 72,405 without AOM use. The adjusted osteoarthritis risk was 27% % lower in AOM users than in non-users (hazard ratio (HR) = 073, 95% CI (0.67-0.79), p < 0.01). Among AOMs, tirzepatide was associated with a significantly lower osteoarthritis (OA) risk compared to semaglutide (HR = 0.57, 95% CI: 0.50-0.65, p < 0.0001). Liraglutide was linked to a significantly higher OA risk vs tirzepatide (HR = 1.63, 95% CI: 1.23-2.15, p = 0.0007). CONCLUSIONS: AOM use was associated with a significantly lower risk of OA and may be an effective obesity management intervention.

A Comparative Analysis on Impact of Extraction Methods on Carotenoids Composition, Antioxidants, Antidiabetes, and Antiobesity Properties in Seagrass Enhalus acoroides: In Silico and In Vitro Study.

Enhalus acoroides, a tropical seagrass, is known for its significant contribution to marine ecosystems and its potential health benefits due to bioactive compounds. This study aims to compare the carotenoid levels in E. acoroides using green extraction via ultrasound-assisted extraction (UAE) and microwave-assisted extraction (MAE) and to evaluate the biological properties of these extracts against oxidative stress, diabetes, and obesity through in silico and in vitro analyses. E. acoroides samples were collected from Manado City, Indonesia, and subjected to UAE and MAE. The extracts were analyzed using UHPLC-ESI-MS/MS to identify carotenoids, including ß-carotene, lutein, lycopene, ß-cryptoxanthin, and zeaxanthin. In silico analysis was conducted to predict the compounds' bioactivity, toxicity, and drug-likeness using WAY2DRUG PASS and molecular docking with CB-Dock2. The compounds C3, C4, and C7 demonstrated notable interactions, with key metabolic proteins and microRNAs, further validating their potential therapeutic benefits. In vitro assays evaluated antioxidant activities using DPPH and FRAP assays, antidiabetic properties through α-glucosidase and α-amylase inhibition, and antiobesity effects via lipase inhibition and MTT assay with 3T3-L1 cells. Results indicated that both UAE and MAE extracts exhibited significant antioxidant, antidiabetic, and antiobesity activities. MAE extracts showed higher carotenoid content and greater biological activity compared to UAE extracts. These findings suggest that E. acoroides, mainly when extracted using MAE, has promising potential as a source of natural bioactive compounds for developing marine-based antioxidant, antidiabetic, and antiobesity agents. This study supplements existing literature by providing insights into the efficient extraction methods and the therapeutic potential of E. acoroides carotenoids.

Adiposity in Chinese people with type 1 diabetes.

Adiposity, synonymous with obesity, is prevalent among both children and adults with type 1 diabetes in China. Recent literature underscored the patho-physiological and socioeconomic factors associated with adiposity, and consistently highlighted its impact on cardiovascular, kidney, and metabolic diseases among Chinese individuals with type 1 diabetes. Addressing and managing adiposity in individuals with type 1 diabetes are complicated and entail comprehensive approaches including lifestyle modifications, cognitive-behavioral therapy, insulin dose titration, and other diabetes treatment medications. The condition calls for coordination among policymakers, researchers, clinicians, and patients.

Piperlongumine inhibits the early stage of adipogenesis in 3T3-L1 cells.

Piperlongumine (PLM), a natural compound isolated from long peppers, has been reported to possess multiple pharmacological roles, including anti-tumor and anti-diabetic. However, the pharmacological role of PLM on adipogenesis is still unknown. In this study, we found that PLM strongly inhibited 3T3-L1 adipocyte differentiation. This inhibition was determined by the accumulation of lipid droplets and intracellular triglycerides. In addition, PLM downregulated both the mRNA and protein expression of adipogenic transcription factors, including CCAAT-enhancer binding proteins ß (C/EBPß), C/EBPα, and peroxisome proliferator-activated receptor γ (PPARγ). Based on the time-course experiment, we found that the inhibitory effect of PLM on adipogenesis was mainly involved in the early stage of adipogenesis. Studying these differential effects could uncover new mechanisms for regulating adipogenesis and new chemicals for treating obesity.

Screening of the Lipid-Lowering Probiotic Lactiplantibacillus Plantarum SDJ09 and its Anti-Obesity Mechanism.

In this study, 39 strains of lactic acid bacteria were screened from several fermented foods. Based on the evaluation of functional and prebiotic properties, Lactiplantibacillus plantarum SDJ09 was selected as a promising candidate. It gave a 48.16% cholesterol reduction and 33.73% pancreatic lipase inhibition in cells; exhibited high resistance to acid, bile salts, and gastrointestinal fluid; and had strong antibacterial activity and high adhesion capabilities. More importantly, the lipid-lowering effect of L. plantarum SDJ09 was also investigated using 3T3-L1 mature adipocytes and HepG2 nonalcoholic fatty liver disease models. L. plantarum SDJ09 effectively decreased triglyceride accumulation by more than 50% in both cell models, in which the expression of PPARγ, C/EBPα, aP2, and LPL in 3T3-L1 cells was significantly downregulated by L. plantarum SDJ09. L. plantarum SDJ09 also improved lipid metabolism by downregulating the expression of HMGCR, SREBP-1c, ACC, and FAS and upregulating the expression of CYP7A1 in HepG2 nonalcoholic steatohepatitis cells. Therefore, L. plantarum SDJ09 has the potential to effectively decrease obesity and non-alcoholic fatty liver disease (NAFLD) by inhibiting lipid accumulation, providing a prospective probiotic agent for anti-obesity.

A review: Polysaccharides targeting mitochondria to improve obesity.

Polysaccharides are one of the most important and widely used bioactive components of natural products, which can be used to treat metabolic diseases. Natural polysaccharides (NPs) have been the subject of much study and research in the field of treating obesity in recent years. Studies in the past have demonstrated that mitochondria are important for the initiation, progression, and management of obesity. Additionally, NPs have the ability to improve mitochondrial dysfunction via a variety of mechanisms. This review summarized the relationship between the structure of NPs and their anti-obesity activity, focusing on the anti-obesity effects of these compounds at the mitochondrial level. We discussed the association between the structure and anti-obesity action of NPs, including molecular weight, monosaccharide composition, glycosidic linkage, conformation and extraction methods. Furthermore, NPs can demonstrate a range of functions in adipose tissue, including but not limited to improving the mitochondrial oxidative respiratory chain, inhibiting oxidative stress, and maintaining mitochondrial mass homeostasis. The purpose of this work is to acquire a thorough understanding of the function that mitochondria play in the anti-obesity effects of NPs and to offer fresh insights for the investigation of how NPs prevent obesity and the creation of natural anti-obesity medications.