Potential Anti-obesity Effects Research Articles

Anti-Obesity Effects of a Collagen with Low Digestibility and High Swelling Capacity: A Human Randomized Control Trial

Background/Objectives: Collagen is a protein formed by very long amino acid chains. When conveniently treated, it can incorporate water into the net, thus increasing its volume and mass. The present work aimed to evaluate the potential anti-obesity effects of bovine collagen that has been technologically treated to increase its water retention capacity in an acid pH medium, with the objective of inducing satiation. Methods: Collagen’s digestibility was tested with a pepsin digestion test. Its swelling capacity was tested in an acid pH medium simulating gastric conditions. Postprandial levels of ghrelin in response to collagen supplementation were tested in rats. In a randomized control trial, 64 subjects with overweight/obesity were allocated in two groups: supplemented daily with two protein bars enriched with collagen (20 g per day) for 12 weeks, or control group. Anthropometric and biochemical measurements were assessed in all the participants. Results: This collagen showed a low digestibility (<60%) and high swelling capacity (>1900%) in vitro. In humans with overweight and obesity, this collagen significantly reduced body weight, body mass index (BMI), systolic blood pressure (SBP), and fatty liver index (FLI) and increased fat-free mass when compared with the control group. A significant reduction in the sarcopenic index; total, troncular, and visceral fat (measured by DEXA); and serum leptin levels were observed in the collagen group at the end of the intervention, with no differences with respect to controls. Collagen reduced the sensation of hunger and increased fullness and satisfaction. In male Wistar rats, collagen decreased postprandial blood ghrelin levels. Conclusions: Collagen supplementation (20 g per day for 12 weeks) reduced body weight, BMI, waist circumference, fat mass, FLI, and SBP in humans with overweight and obesity, which might be related to the increased sensation of fullness and satisfaction reported by the volunteers after the intake.

Potential Anti-Obesity Effect of Hazel Leaf Extract in Mice and Network Pharmacology of Selected Polyphenols

Background: Obesity is gradually becoming a widespread health problem, and treatment using natural compounds has seen an increasing trend. As a by-product of hazelnut, hazel leaf is usually disposed of as waste, but it is widely used in traditional and folk medicines around the world. Aim of this study: Based on previous studies, the effects of the regulation of lipid metabolism and the mechanism of hazel leaf polyphenol extraction obesity were investigated. Methods: In this study, a high-fat diet-fed mouse model of obesity and 3T3-L1 preadipocytes were established. The ameliorative effects of the hazel leaf polyphenol extract on obesity and the regulating lipid metabolisms were explored based on network pharmacology, gut microbiota, and molecular docking. Results: Network pharmacology showed that hazel leaf polyphenols may play a role by targeting key targets, including PPARγ, and regulating the PPAR signaling pathway. They significantly improved body weight gain, the liver index, and adiposity and lipid levels; regulated the gut microbiota and short-chain fatty acid contents; down-regulated the expression of lipid synthesis proteins SREBP1c, PPARγ, and C/EBP-α; and up-regulated the expression of p-AMPK in obese mice. They inhibited the differentiation of 3T3-L1 cells, and the expression of related proteins is consistent with the results in vivo. The molecular docking results indicated that gallic acid, quercetin-3-O-beta-D-glucopyranoside, quercetin, myricetin, and luteolin-7-O-glucoside in the hazel leaf polyphenol extract had strong binding activities with PPARγ, C/EBP-α, and AMPK. Conclusions: The results demonstrate that the hazel leaf polyphenol extract can improve obesity by regulating lipid metabolism, which provides a valuable basis for developing health products made from hazel leaf polyphenols in the future.

Efficacy of Probiotics in Overweight and Obesity Control: An Umbrella Review and Subgroup Meta-Analysis.

Numerous primary and secondary studies have consistently demonstrated that probiotics, including lactobacillus and Bifidobacterium, possess a potential anti-obesity effect. However, it is worth noting that some studies have yielded contrasting results. Considering this, our study aims to present a comprehensive overview of published systematic reviews and meta-analyses, focusing on the efficacy and safety of probiotics in managing obesity. To achieve this objective, we conducted an umbrella review following the PRISMA protocol and Cochrane guidelines. We searched databases such as Embase, PubMed, Cochrane Library, and Google Scholar for relevant systematic reviews and meta-analyses published in English, without imposing any date restrictions. Our inclusion criteria encompassed studies evaluating the anti-obesity impact of probiotics, with a specific focus on changes in body mass index (BMI), fat mass percentage (FMP), body weight (BW), and body fat mass (BFM). These studies were meticulously reviewed by two independent reviewers. Our analysis included five systematic reviews and 18 meta-analyses that met the predefined inclusion and exclusion criteria. The meta-analyses revealed statistically significant reductions in the following parameters: BMI, a decrease of 0.30kg/m2 (p < 0.00001, 95% CI - 0.36 to - 0.25); BFM, a reduction of 0.86kg (p < 0.00001, 95% CI - 1.02 to - 0.71); BW, a decrease of 0.59kg (p < 0.00001, 95% CI - 0.74 to - 0.44); and FMP, a substantial decline of 78% (p < 0.00001, 95% CI - 1.02 to - 0.54). In summary, our umbrella review suggests that existing evidence supports the potential benefits of probiotics in managing obesity and overweight. However, it is essential to acknowledge that the credibility of this evidence is somewhat limited due to the inclusion of studies with poor-quality designs and relatively small participant numbers. To establish the true efficacy of probiotics in obesity management, we recommend conducting robust studies involving larger participant cohorts.

Royal Jelly Exerts a Potent Anti-Obesity Effect in Rats by Activating Lipolysis and Suppressing Adipogenesis.

Background/Objective: This study examined the anti-obesity effect of royal jelly (RJ) in rats fed with a high-fat diet by targeting the major pathways involved in adipogenesis and lipolysis. In addition, it examined whether this effect is AMPK-dependent. Methods: Five groups of adult male albino rats were used (n = 6 each as 1); the control rats were fed with a normal diet (2.9 kcal), and the other groups were as follows: control + RJ (300 mg/kg), HFD (4.75 kcal), HFD + RJ (300 mg/kg), and HFD + RJ (300 mg/kg) + dorsomorphin (an AMPK inhibitor) (0.2 mg/kg). Results: RJ was administered orally to all rats. With no changes in food and energy intake, RJ significantly reduced gains in body weight, fat weight, body mass index (BMI), the Lee index, abdominal circumference (AC), and the adiposity index (AI). It also reduced fasting glucose and insulin levels, HOMA-IR, and the circulatory levels of free fatty acids (FFAs), triglycerides, cholesterol, and LDL-c in the HFD-fed rats. RJ also increased serum glycerol levels and adiponectin levels, but reduced the serum levels of leptin, IL-6, and TNF-α. Moreover, RJ reduced the secretion of IL-6 and TNF-α from isolated WAT. At the tissue level, the HFD + RJ rats exhibited a smaller adipocyte size compared to the HFD rats. At the molecular level, RJ increased the phosphorylation of AMPK, SREBP1, and ACC-1 and increased the mRNA and protein levels of HSL and ATG in the WAT of the HFD rats. In concomitance, RJ increased the mRNA levels of PGC-α1, reduced the protein levels of PPARγ, and repressed the transcriptional activities of PPARγ, SREBP1, and C/EBPαβ in the WAT of these rats. All the aforementioned effects of RJ were prevented by co-treatment with dorsomorphin. Conclusions: RJ exerts a potent anti-obesity effect in rats that is mediated by the AMPk-dependent suppression of WAT adipogenesis and the stimulation of lipolysis.

Identification of novel anti-obesity saponins from the ovary of sea cucumber (Stichopus japonicus)

The potential anti-obesity effects of sea cucumber extract have been reported. However, the individual saponins responsible for these effects are yet to be isolated and characterized. This study aimed to identify the most effective sea cucumber body part for inhibiting lipid accumulation in adipocytes and to elucidate the compounds responsible for this effect using nuclear magnetic resonance (NMR) techniques. Sea cucumber ovary 80 % ethanol extract (SCOE) demonstrated remarkable efficacy in inhibiting adipocyte differentiation compared to other sea cucumber body parts with 50 % or 80 % ethanol extracts. SCOE anti-obesity effect was evaluated in C57BL/6 mice fed a high-fat diet, which revealed significant reductions in body weight, serum lipids, adipose tissue, and liver weight. Using column chromatography, eight saponins were isolated from the SCOE, four of which exhibited potent inhibitory effects on adipocyte differentiation. Of these, three active saponins, holotoxins A, B, and D1, were newly identified. These findings highlight the potential of SCOE and its saponins as effective anti-obesity agents.

Anti-Obesity Activity of Sanghuangporus vaninii by Inhibiting Inflammation in Mice Fed a High-Fat Diet.

Obesity is an unhealthy condition associated with various diseases characterized by excess fat accumulation. However, in China, the prevalence of obesity is 14.1%, and it remains challenging to achieve weight loss or resolve this issue through clinical interventions. Sanghuangpours vaninii (SPV) is a nutritional fungus with multiple pharmacological activities and serves as an ideal dietary intervention for combating obesity. In this study, a long-term high-fat diet (HFD) was administered to induce obesity in mice. Different doses of SPV and the positive drug simvastatin (SV) were administered to mice to explore their potential anti-obesity effects. SPV regulated weight, serum lipids, and adipocyte size while inhibiting inflammation and hepatic steatosis. Compared with the vehicle-treated HFD-fed mice, the lowest decreases in total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) were 9.72%, 9.29%, and 12.29%, respectively, and the lowest increase in high-density lipoprotein cholesterol (HDL-C) was 5.88% after treatment with different doses of SPV. With SPV treatment, the analysis of gut microbiota and serum lipids revealed a significant association between lipids and inflammation-related factors, specifically sphingomyelin. Moreover, Western blotting results showed that SPV regulated the toll-like receptor (TLR4)/nuclear factor kappa B (NF-κB) signaling pathway in HFD-diet mice, which is related to inflammation and lipid metabolism. This research presents empirical proof of the impact of SPV therapy on obesity conditions.

Modulatory Effects of Lactobacillus paracasei-Fermented Turmeric on Metabolic Dysregulation and Gut Microbiota in High-Fat Diet-Induced Obesity in Mice.

Turmeric, derived from Curcuma longa, and Lactobacillus paracasei, a lactic acid bacteria, have been studied for their potential antiobesity effects. To date, the antiobesity effects of turmeric fermented with L. paracasei have not been sufficiently investigated. This study was conducted via oral administration of 5% L. paracasei-fermented (FT) and unfermented turmeric (UT) in diet over 16 weeks using high-fat diet (HFD)-induced obese C57BL/6J mice. Results showed that the curcuminoid content of turmeric decreased following fermentation. Furthermore, FT significantly suppressed weight gain and liver and visceral adipose tissue weight and reduced plasma metabolic parameters in both the UT and FT experimental groups. The effects of FT were more noticeable than those of the unfermented form. Moreover, FT downregulated the expression of adipogenesis, lipogenesis, and inflammatory-related protein, but upregulated liver β-oxidation protein SIRT 1, PPARα, and PGC-1α in perigonadal adipose tissue. Additionally, FT ameliorated insulin resistance by activating insulin receptor pathway protein expressions in visceral adipose tissues. FT also modulated gut microbiota composition, particularly in two beneficial bacteria, Akkermansia muciniphila and Desulfovibrio, as well as two short-chain fatty acid-producing bacteria: Muribaculum intestinale and Deltaproteobacteria. Our findings indicate that the modulation effect of FT may be an important pathway for its antiobesity mechanisms.

Apigenin improves testosterone synthesis by regulating endoplasmic reticulum stress

Obesity is a growing epidemic among reproductive-age men, which can cause and exacerbate male infertility by means of associated comorbidities, endocrine abnormalities, and direct effects on the fidelity and throughput of spermatogenesis. A prominent consequence of male obesity is a reduction in testosterone levels. Natural products have shown tremendous potential anti-obesity effects in metabolic diseases. This study aimed to investigate the potential of apigenin (AP) to alleviate testicular dysfunction induced by a high-fat diet (HFD) and to investigate the underlying mechanisms, focusing on endoplasmic reticulum stress (ERS) and testosterone synthesis. A murine model of obesity was established using HFD-fed mice. The effects of AP on obesity, lipid metabolism, testicular dysfunction, and ERS were assessed through various physiological, histological, and molecular techniques. Administration of AP (10 mg/kg) ameliorated HFD-induced obesity and testicular dysfunction in a mouse model, as evidenced by decreased body weight, improved lipid profiles and testicular pathology, and restored protein levels related to testosterone. Furthermore, in vitro studies demonstrated that AP relieved ERS and recovered testosterone synthesis in murine Leydig cells (TM3) treated with free fatty acids (FFAs). It was also observed that AP rescued testosterone synthesis enzymes in TM3 cells, similar to that observed with the inhibitor of the PERK pathway (GSK2606414). In addition, ChIP, qPCR, and gene silencing showed that the C/EBP homologous protein (CHOP) bound directly to the promoter region of steroidogenic STAR and negatively modulated its expression. Collectively, AP has remarkable potential to alleviate HFD-induced obesity and testicular dysfunction. Its protective effects are attributable partly to mitigating ERS and restoring testosterone synthesis in Leydig cells.

Barley Protein LFBEP-C1 from Lactiplantibacillus plantarum dy-1 Fermented Barley Extracts by Inhibiting Lipid Accumulation in a Caenorhabditis elegans Model

ObjectiveThis study aimed to investigate the lipid-lowering activity of LFBEP-C1 in high glucose-fed Caenorhabditis elegans (C. elegans). MethodsIn this study, the fermented barley protein LFBEP-C1 was prepared and tested for its potential anti-obesity effects on C. elegans. The worms were fed Escherichia coli OP50 (E. coli OP50), glucose, and different concentrations of LFBEP-C1. Body size, lifespan, movement, triglyceride content, and gene expression were analyzed. The results were analyzed using ANOVA and Tukey's multiple comparison test. ResultsCompared with the model group, the head-swing frequency of C. elegans in the group of LFBEP-C1 at 20 μg/mL increased by 33.88%, and the body-bending frequency increased by 27.09%. This indicated that LFBEP-C1 improved the locomotive ability of C. elegans. The average lifespan of C. elegans reached 13.55 days, and the body length and width of the C. elegans decreased after LFBEP-C1 intake. Additionally, LFBEP-C1 reduced the content of lipid accumulation and triglyceride levels. The expression levels of sbp-1, daf-2, and mdt-15 significantly decreased, while those of daf-16, tph-1, mod-1, and ser-4 significantly increased after LFBEP-C1 intake. Changes in these genes explain the signaling pathways that regulate lipid metabolism. ConclusionLFBEP-C1 significantly reduced lipid deposition in C. elegans fed a high-glucose diet and alleviated the adverse effects of a high-glucose diet on the development, lifespan, and exercise behavior of C. elegans. In addition, LFBEP-C1 regulated lipid metabolism mainly by mediating the expression of genes in the sterol regulatory element-binding protein, insulin, and 5-hydroxytryptamine signaling pathways.

Effects of complex polysaccharides by Ficus carica Linn. polysaccharide and peach gum on the development and metabolites of human gut microbiota

Both Ficus carica Linn. polysaccharide and peach gum had beneficial effects on human gut microbiota. However, their complex polysaccharides have never been studied during the fecal fermentation in vitro. Therefore, this study investigated the effects of Ficus carica Linn. polysaccharide (FCPS), peach gum polysaccharide (PGPS) and their complex polysaccharides on fecal fermentation characteristics and gut microbiota composition in vitro. The changes of pH, gas production and short-chain fatty acids (SCFAs) in the metabolites were measured at 0, 6, 9, 12 and 24 h under anaerobic conditions. The changes of gut microbiota were measured at 24 h. The results of metabolite determination showed that FCPS and FCPG2_1 had strong acid production, pH reduction and gas production ability, while the PGPS had poor effect. The results of gut microbiota analysis showed that Firmicutes, Bacteroidetes and Proteobacteria were the dominant phyla in the fermentation process, and the ratio of Firmicutes to Bacteroidetes was the lowest in the FCPG1_1. At the genus level, the promoting effects of these five polysaccharides on different genera were different. FCPS notably augmented the proliferation of Bacteroides and Phascolarctobacterium. Similarly, FCPG1_1 significantly enhanced the growth of Faecalibacterium and Paraprevotella. Furthermore, FCPG2_1 was responsible for an upsurge in the proliferation of the Lachnospiraceae_NK4A136_group, whereas PGPS proved excellent in stimulating Roseburia's growth. In summary, complex polysaccharides and FCPS were better, and they had potential anti-obesity effects. This study had practical significance for the development of functional food and dietary intervention.

Evaluation of Anti-Obesity and Antidiabetic Activities of Orostachys japonicus in Cell and Animal Models.

Orostachys japonicus is a popular traditional medicinal herb used in Asian countries. This study is focused on evaluating its role in lipid and glucose metabolism in cell and animal models to establish the plant as an anti-obesity and antidiabetic herb. A butanol fraction of O. japonicus was used in the study. The lipid production was evaluated by the Oil Red O technique while the expression of adipogenic markers by Western blotting and RT-PCR using 3T3-L1 preadipocyte. The effect on glucose uptake activity was evaluated in C2C12 myoblast cells. The animal study was carried out in C57BL mice to evaluate anti-obesity activity using the high-fat diet model. The evaluation of serum lipid, blood glucose, adipogenic and fibrosis markers in the liver, and fat deposition in the liver and adipose tissue (by histology) of mice was conducted. Butanol fraction of O. japonicus significantly inhibited the lipid production in the 3T3-L1 cells and reduced the expression of PPARγ, C/EBPα, SREBP-1c and aP2. It enhanced glucose uptake in insulin-resistant C2C12 myoblast cells. It reduced body weight, triglycerides, and blood glucose in the obese mice. It significantly inhibited lipid accumulation in the liver and adipose tissue of obese mice along with suppression of expression of adipogenic and fibrosis markers in the liver. In summary, supporting the previous results, this study helped to establish the potent anti-obesity, antidiabetic, and liver-protecting effect of the butanol fraction of O. japonicus.

Isolation of Lactobacillus acidophilus strain and its anti-obesity effect in a diet induced obese murine model.

Intestinal microbiota is a potential determinant of obesity, with probiotic bile salt hydrolase (BSH) as one of the key mechanisms in the anti-obesity effects. In this study, we present a Lactobacillus acidophilus GOLDGUT-LA100 (LA100) with high BSH activity, good gastric acid and bile salt tolerance, and a potential anti-obesity effect. LA100's anti-obesity effects were evaluated in a high-fat diet-induced, obese mouse model. LA100 administration alleviates high-fat diet-induced pathophysiological symptoms, such as body weight gain, high serum glucose and cholesterol level, hepatic lipid accumulation, and adipose inflammation. These results demonstrate concrete anti-obesity benefit in animal models and show promising applications in future clinical studies.

Potential anti-obesity effect of saponin metabolites from adzuki beans: A computational approach.

In contrast to its widespread traditional and popular culinary use to reduce weight, Vigna angularis (adzuki beans) was not subjected to sufficient scientific scrutiny. Particularly, its saponins whose role was never investigated before to unveil the beans' antidiabetic and anti-obesity effects. Four vital pancreatic and intestinal carbohydrate enzymes were selected to assess the potency of the triterpenoidal saponins of V. angularis to bind and activate these proteins through high-precision molecular modeling and dynamics mechanisms with accurate molecular mechanics Generalized Born Surface Area (MMGBSA) energy calculations; thus, recognizing their anti-obesity potential. Our results showed that adzukisaponin VI and adzukisaponin IV were the best compounds in the α-amylase and α-glucosidase enzymatic grooves, respectively. Adzukisaponin VI and angulasaponin C were the best fitting in the N-termini of sucrase-isomaltose (SI) enzyme, and angulasaponin C was the best scoring compound in maltase-glucoamylase C-termini. All of them outperformed the standard drug acarbose. These compounds in their protein complexes were selected to undergo molecular simulations of the drug-bound protein compared to the apo-protein through 100 ns, which confirmed the consistency of binding to the key amino acid residues in the four enzyme pockets with the least propensity of unfolding. Detailed analysis is given of the different polar and hydrophobic binding interactions of docked compounds. While maltase-adzukisaponin VI complex scored the lowest MMGBSA free energy of -67.77 Kcal/mol, α-amylase complex with angulasaponin B revealed the free binding energy of -74.18 Kcal/mol with a dominance of van der Waals energy (ΔEVDW) and the least change from the start to the end of the simulation time. This study will direct researchers to the significance of isolating the pure adzuki saponin components to conduct future invitro and invivo experimental works and even clinical trials.

Profiles of Intestinal Flora in Breastfed Obese Children and Selecting Functional Strains Against Obesity.

Breast milk has the potential to prevent childhood obesity by providing probiotics, but there are still instances of obesity in breastfed children. This study investigates the difference in intestinal flora structure between breastfed children with obesity (OB-BF) and normal-weight breastfed children (N-BF). Building upon this foundation, it employs both cell and mouse models to identify an antiobesity strain within the fecal matter of N-BF children and explore its underlying mechanisms. The results reveal a reduction in lactobacillus levels within the intestinal flora of OB-BF children compared to N-BF children. Consequently, Lactobacillus plantarum H-72 (H-72) is identified as a promising candidate due to its capacity to stimulate glucagon-like peptide-1 (GLP-1) secretion in enteroendocrine cells (ECCs). In vivo, H-72 effectively increases serum GLP-1 concentration, reduces food intake, regulates the expression of genes related to energy metabolism (SCD-1, FAS, UCP-1, and UCP-3), and regulates gut microbiota structure in mice. Moreover, the lipoteichoic acid of H-72 activates toll-like receptor 4 to enhanced GLP-1 secretion in STC-1 cells. L. plantarum H-72 is screened out for its potential antiobesity effect, which presents a potential and promising avenue for future interventions aimed at preventing pediatric obesity in breastfed children.

Flavonoid extracts of Citrus aurantium L. var. amara Engl. Promote browning of white adipose tissue in high-fat diet-induced mice

Ethnopharmacological relevanceObesity has become a public burden worldwide due to its booming incidence and various complications, and browning of white adipose tissue (WAT) is recognized as a hopeful strategy to combat it. Blossom of Citrus aurantium L. var. amara Engl. (CAVA) is a popular folk medicine and dietary supplement used for relieving dyspepsia, which is recorded in the Chinese Materia Medica. Our previous study showed that blossom of CAVA had anti-obesity potential, while its role in browning of WAT was still unclear. Aim of the studyThis study aimed to characterize the constituents in flavonoids from blossom of CAVA (CAVAF) and to clarify the anti-obesity capacities especially the effects on browning of WAT. Materials and methodsGradient ethanol eluents from blossom of CAVA were obtained by AB-8 macroporous resin. 3T3-L1 cells and pancreatic lipase inhibition assay were employed to investigate the potential anti-obesity effects in vitro. HPLC and UPLC/MS assays were performed to characterize the chemical profiles of different eluents. Network pharmacology and molecular docking assays were used to reveal potential anti-obesity targets. Furthermore, high-fat diet (HFD)-induced mice were constructed to explore the anti-obesity actions and mechanisms in vivo. Results30% ethanol eluents with high flavonoid content and great inhibition on proliferation of 3T3-L1 preadipocytes and pancreatic lipase activity were regarded as CAVAF. 19 compounds were identified in CAVAF. Network pharmacology analysis demonstrated that AMPK and PPARα were potential targets for CAVAF in alleviating obesity. Animal studies demonstrated that CAVAF intervention significantly decreased the body weight, WAT weight, serum TG, TC and LDL-C levels in HFD-fed obese mice. HFD-induced insulin resistance and morphological changes in WAT and brown adipose tissue were also markedly attenuated by CAVAF treatment. CAVAF supplementation potently inhibited iWAT inflammation by regulating IL-6, IL-1β, TNF-α and IL-10 mRNA expression in iWAT of mice. Furthermore, the gene expression levels of thermogenic markers including Cyto C, ATP synthesis, Cidea, Cox8b and especially UCP1 in iWAT of mice were significantly up-regulated by CAVAF administration. CAVAF intervention also markedly increased the expression levels of PRDM16, PGC-1α, SIRT1, AMPK-α1, PPARα and PPARγ mRNA in iWAT of mice. ConclusionCAVAF treatment significantly promoted browning of WAT in HFD-fed mice. These results suggested that flavonoid extracts from blossom of CAVA were probably promising candidates for the treatment of obesity.

A New Strategy for Obesity Treatment: Revealing the Frontiers of Anti-obesity Medications.

Obesity dramatically increases the risk of type 2 diabetes, fatty liver, hypertension, cardiovascular disease, and cancer, causing both declines in quality of life and life expectancy, which is a serious worldwide epidemic. At present, more and more patients with obesity are choosing drug therapy. However, given the high failure rate, high cost, and long design and testing process for discovering and developing new anti-obesity drugs, drug repurposing could be an innovative method and opportunity to broaden and improve pharmacological tools in this context. Because different diseases share molecular pathways and targets in the cells, anti-obesity drugs discovered in other fields are a viable option for treating obesity. Recently, some drugs initially developed for other diseases, such as treating diabetes, tumors, depression, alcoholism, erectile dysfunction, and Parkinson's disease, have been found to exert potential anti-obesity effects, which provides another treatment prospect. In this review, we will discuss the potential benefits and barriers associated with these drugs being used as obesity medications by focusing on their mechanisms of action when treating obesity. This could be a viable strategy for treating obesity as a significant advance in human health.

Tibetan tea consumption prevents obesity by modulating the cellular composition and metabolic reprogramming of white adipose tissue.

Obesity, a global health concern, is linked with numerous metabolic and inflammatory disorders. Tibetan tea, a traditional Chinese beverage rich in theabrownin, is investigated in this study for its potential anti-obesity effects. Our work demonstrates that Tibetan tea consumption in C57BL/6J mice significantly mitigates obesity-related phenotypic changes without altering energy intake. Computational prediction revealed that Tibetan tea consumption reconstructs gene expression in white adipose tissue (WAT), promoting lipid catabolism and thereby increasing energy expenditure. We also note that Tibetan tea suppresses inflammation in WAT, reducing adipocyte hyperplasia and immune cell infiltration. Furthermore, Tibetan tea induces profound metabolic reprogramming, influencing amino acid metabolic pathways, specifically enhancing glutamine synthesis, which in turn suppresses pro-inflammatory chemokine production. These findings highlight Tibetan tea as a potential candidate in obesity prevention, providing a nuanced understanding of its capacity to modulate the cellular composition and metabolic landscape of WAT.

Toxicological Evaluation of a Polyherbal Formulation (18KHT01) and Validation of UPLC-DAD Method for Quality Control.

Background: 18KHT01 is a novel synergistic composition of Quercus acutissima, Camellia sinensis, Geranium thunbergii, and a small portion of Citrus limon. Our previous report demonstrated that the 18KHT01 exhibits potent antiobesity effects, with synergistic antioxidant, antiadipogenic, and antiobesity activities in diet-induced obese mice. This study explores the toxicity profile and quality control parameters of the 18KHT01 formulation. Methods: Broad-spectrum acute and subacute oral toxicity studies were performed using male and female ICR mice. In order to simultaneous analysis of the 18KHT01 formulation, an ultraperformance liquid chromatography coupled with a diode array detector (UPLC-DAD) method was developed and validated using six marker compounds. Results: Acute oral toxicity evaluation of 18KHT01, administered at single high doses of 2, 2.5, 3, and 5 g/kg, identified 2 g/kg as the no-observed adverse effect level (NOAEL). The LD50 (50% lethal dose) and LD100 (100% lethal dose) of 18KHT01 for male ICR mice were 3.99 and 7.77 g/kg, and those for the female mice were 2.94 and 4.70 g/kg, respectively. In addition, a 30-day repeated dose oral subacute toxicity evaluation indicated that 18KHT01 is safe below 500 mg/kg/day for long-term administration in ICR mice of either sex. UPLC-DAD method validation revealed that each calibration curve for the marker compounds showed good linearity, as well as the validation parameters such as precision, specificity, and accuracy met the acceptance criteria. Conclusion: The present study evidenced the toxicological profile of 18KHT01 polyherbal formulation in mice as well as developed a simple, rapid, and accurate chromatographic method for quality control.

Sesamin and sesamolin potentially inhibit adipogenesis through downregulating the peroxisome proliferator-activated receptor γ protein expression and activity in 3T3-L1 cells

Sesamin and sesamolin are major sesame lignans that have demonstrated anti-inflammatory, anticancer, and neuroprotective properties and potential benefits in the liver, cardiovascular diseases, and metabolic syndrome. However, despite previous research on their antiobesity effects and underlying mechanisms, a comprehensive investigation of these aspects is still lacking. In this study, we evaluated the regulatory effects of 20 to 80 µM sesamin and sesamolin on adipogenesis in vitro using 3T3-L1 cells as a model cell line. We hypothesized that the lignans would inhibit adipogenic differentiation in 3T3-L1 cells through the regulation of peroxisome proliferator-activated receptor γ (PPARγ). Our data indicate that sesamin and sesamolin inhibited the adipogenic differentiation of 3T3-L1 cells by dose-dependently decreasing lipid accumulation and triglyceride formation. Sesamin and sesamolin reduced the mRNA and protein expression of the adipogenesis-related transcription factors, PPARγ and CCAAT/enhancer-binding protein α, leading to the dose-dependent downregulations of their downstream targets, fatty acid binding protein 4, hormone-sensitive lipase, lipoprotein lipase, and glucose transporter 4. In addition, glucose uptake was dose-dependently attenuated by sesamin and sesamolin in both differentiated 3T3-L1 cells and HepG2 cells. Interestingly, our results suggested that sesamin and sesamolin might directly bind to PPARγ to inhibit its transcriptional activity. Finally, sesamin and sesamolin decreased the phosphorylation of 3 mitogen-activated protein kinase signaling components in differentiated 3T3-L1 cells. Taken together, our findings suggest that sesamin and sesamolin may exhibit antiobesity effects by potentially downregulating PPARγ and its downstream genes through the mitogen-activated protein kinase signaling pathway, offering important insights into the molecular mechanisms underlying the potential antiobesity effects of sesamin and sesamolin.

Effects of Cinnamon (Cinnamomum zeylanicum) Extract on Adipocyte Differentiation in 3T3-L1 Cells and Lipid Accumulation in Mice Fed a High-Fat Diet.

Flavonoids and phenolic acid are two of the rich polyphenols found in cinnamon (Cinnamomum zeylanicum). The effects of cinnamon extract on the inhibition of adipocyte differentiation in 3T3-L1 fibroblast cells and prohibitory lipid accumulation in male mice fed a high-fat diet were examined. Upon treating 3T3-L1 cells with cinnamon for 3 days, the cinnamon inhibited lipid accumulation and increased gene expression levels, such as those of adiponectin and leptin. In in vivo experiments, mice were randomized into four groups after a one-week acclimation period, as follows: normal diet, normal diet + 1% cinnamon extract, high-fat diet, and high-fat diet + 1% cinnamon extract. After 14 weeks of supplementation, we found that cinnamon extract increased the expression of lipolysis-related proteins, such as AMPK, p-ACC, and CPT-1, and reduced the expression of lipid-synthesis-related proteins, such as SREBP-1c and FAS, in liver tissue. Our results show that cinnamon extract may exhibit anti-obesity effects via the inhibition of lipid synthesis and adipogenesis and the induction of lipolysis in both 3T3-L1 fibroblast cells and mice fed a high-fat diet. Accordingly, cinnamon extract may have potential anti-obesity effects.