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1.
Pak J Pharm Sci ; 37(1(Special)): 231-234, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38747274

ABSTRACT

Increased levels of bad cholesterol in the body result in increasing blood pressure and weight gain. The rate of mortality in people, especially who are obese, is increasing due to absence of organic sources of fiber in their diets. Chia and fennel seeds are rich sources of fiber. The objective of this study was to evaluate the combined effect of Salvia hispanica (Chia seeds) and Foeniculum vulgare (Fennel seeds) against weight-loss and lipid profile in obese human subjects. The research was conducted on obese people aged 25 to 40 years at the Jinnah Hospital Lahore. The study design was randomized control trial (RCT). The sample size was calculated and was divided in-to two groups. With the duration of study being 3 months, pre-testing of all the participants was done. Group 1 was control group, given placebo treatment and Group 2 was an intervention group and given chia and fennel seeds. Post-testing was done and data were analyzed. Results showed that chia and fennel seeds have significant effect (p <0.05) on BMI and lipid profile hence, both are beneficial for lowering body weight and improving LDL, HDL, serum triglycerides and total cholesterol levels.


Subject(s)
Foeniculum , Obesity , Salvia , Seeds , Weight Loss , Humans , Foeniculum/chemistry , Adult , Obesity/blood , Obesity/drug therapy , Seeds/chemistry , Salvia/chemistry , Female , Male , Weight Loss/drug effects , Lipids/blood , Plant Extracts/pharmacology , Anti-Obesity Agents/pharmacology , Anti-Obesity Agents/therapeutic use , Body Mass Index , Phytotherapy
4.
Cells ; 13(10)2024 May 18.
Article in English | MEDLINE | ID: mdl-38786092

ABSTRACT

The early stages of life, especially the period from conception to two years, are crucial for shaping metabolic health and the risk of obesity in adulthood. Adipose tissue (AT) plays a crucial role in regulating energy homeostasis and metabolism, and brown AT (BAT) and the browning of white AT (WAT) are promising targets for combating weight gain. Nutritional factors during prenatal and early postnatal stages can influence the development of AT, affecting the likelihood of obesity later on. This narrative review focuses on the nutritional programming of AT features. Research conducted across various animal models with diverse interventions has provided insights into the effects of specific compounds on AT development and function, influencing the development of crucial structures and neuroendocrine circuits responsible for energy balance. The hormone leptin has been identified as an essential nutrient during lactation for healthy metabolic programming against obesity development in adults. Studies have also highlighted that maternal supplementation with polyunsaturated fatty acids (PUFAs), vitamin A, nicotinamide riboside, and polyphenols during pregnancy and lactation, as well as offspring supplementation with myo-inositol, vitamin A, nicotinamide riboside, and resveratrol during the suckling period, can impact AT features and long-term health outcomes and help understand predisposition to obesity later in life.


Subject(s)
Micronutrients , Obesity , Humans , Animals , Obesity/metabolism , Micronutrients/pharmacology , Micronutrients/metabolism , Adipose Tissue, Brown/drug effects , Adipose Tissue, Brown/metabolism , Female , Pregnancy , Adipose Tissue/metabolism , Adipose Tissue/drug effects , Anti-Obesity Agents/pharmacology , Anti-Obesity Agents/therapeutic use
5.
Int J Mol Sci ; 25(9)2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38731918

ABSTRACT

In the age of information technology and the additional computational search tools and software available, this systematic review aimed to identify potential therapeutic targets for obesity, evaluated in silico and subsequently validated in vivo. The systematic review was initially guided by the research question "What therapeutic targets have been used in in silico analysis for the treatment of obesity?" and structured based on the acronym PECo (P, problem; E, exposure; Co, context). The systematic review protocol was formulated and registered in PROSPERO (CRD42022353808) in accordance with the Preferred Reporting Items Checklist for Systematic Review and Meta-Analysis Protocols (PRISMA-P), and the PRISMA was followed for the systematic review. The studies were selected according to the eligibility criteria, aligned with PECo, in the following databases: PubMed, ScienceDirect, Scopus, Web of Science, BVS, and EMBASE. The search strategy yielded 1142 articles, from which, based on the evaluation criteria, 12 were included in the systematic review. Only seven these articles allowed the identification of both in silico and in vivo reassessed therapeutic targets. Among these targets, five were exclusively experimental, one was exclusively theoretical, and one of the targets presented an experimental portion and a portion obtained by modeling. The predominant methodology used was molecular docking and the most studied target was Human Pancreatic Lipase (HPL) (n = 4). The lack of methodological details resulted in more than 50% of the papers being categorized with an "unclear risk of bias" across eight out of the eleven evaluated criteria. From the current systematic review, it seems evident that integrating in silico methodologies into studies of potential drug targets for the exploration of new therapeutic agents provides an important tool, given the ongoing challenges in controlling obesity.


Subject(s)
Computer Simulation , Obesity , Humans , Obesity/drug therapy , Obesity/metabolism , Animals , Molecular Docking Simulation , Anti-Obesity Agents/pharmacology , Anti-Obesity Agents/therapeutic use , Lipase/metabolism , Lipase/antagonists & inhibitors , Molecular Targeted Therapy/methods
6.
Int J Mol Sci ; 25(9)2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38732125

ABSTRACT

"Ganghwal" is a widely used herbal medicine in Republic of Korea, but it has not been reported as a treatment strategy for obesity and diabetes within adipocytes. In this study, we determined that Ostericum koreanum extract (OKE) exerts an anti-obesity effect by inhibiting adipogenesis and an anti-diabetic effect by increasing the expression of genes related to glucose uptake in adipocytes and inhibiting α-glucosidase activity. 3T3-L1 preadipocytes were differentiated for 8 days in methylisobutylxanthine, dexamethasone, and insulin medium, and the effect of OKE was confirmed by the addition of 50 and 100 µg/mL of OKE during the differentiation process. This resulted in a reduction in lipid accumulation and the expression of PPARγ (Peroxisome proliferator-activated receptor γ) and C/EBPα (CCAAT enhancer binding protein α). Significant activation of AMPK (AMP-activated protein kinase), increased expression of GLUT4 (Glucose Transporter Type 4), and inhibition of α-glucosidase activity were also observed. These findings provide the basis for the anti-obesity and anti-diabetic effects of OKE. In addition, OKE has a significant antioxidant effect. This study presents OKE as a potential natural product-derived material for the treatment of patients with metabolic diseases such as obesity- and obesity-induced diabetes.


Subject(s)
3T3-L1 Cells , Adipocytes , Adipogenesis , Anti-Obesity Agents , Hypoglycemic Agents , PPAR gamma , Plant Extracts , Mice , Plant Extracts/pharmacology , Plant Extracts/chemistry , Animals , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use , Adipogenesis/drug effects , Adipocytes/drug effects , Adipocytes/metabolism , PPAR gamma/metabolism , PPAR gamma/genetics , Anti-Obesity Agents/pharmacology , Obesity/drug therapy , Obesity/metabolism , Glucose Transporter Type 4/metabolism , Glucose Transporter Type 4/genetics , CCAAT-Enhancer-Binding Protein-alpha/metabolism , CCAAT-Enhancer-Binding Protein-alpha/genetics , alpha-Glucosidases/metabolism , AMP-Activated Protein Kinases/metabolism , Antioxidants/pharmacology , Glycoside Hydrolase Inhibitors/pharmacology , Crassulaceae/chemistry , Lipid Metabolism/drug effects , Cell Differentiation/drug effects
7.
J Microbiol Biotechnol ; 34(5): 1073-1081, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38719777

ABSTRACT

Obesity is spawned by an inequality between the portion of energy consumed and the quantity of energy expended. Disease entities such as cardiovascular disease, arteriosclerosis, hypertension, and cancer, which are correlated with obesity, influence society and the economy. Suppression of adipogenesis, the process of white adipocyte generation, remains a promising approach for treating obesity. Oil Red O staining was used to differentiate 3T3-L1 cells for screening 20 distinct Lactobacillus species. Among these, Lactobacillus acidophilus DS0079, referred to as YBS1, was selected for further study. YBS1 therapy decreased 3T3-L1 cell development. Triglyceride accumulation and mRNA expression of the primary adipogenic marker, peroxisome proliferator-activated receptor gamma (PPARγ), including its downstream target genes, adipocyte fatty acid binding protein 4 and adiponectin, were almost eliminated. YBS1 inhibited adipocyte differentiation at the early stage (days 0-2), but no significant difference was noted between the mid-stage (days 2-4) and late-stage (days 4-6) development. YBS1 stimulated the activation of p38 mitogen-activated protein kinase (p38 MAPK) during the early stages of adipogenesis; however, this effect was eliminated by the SB203580 inhibitor. The data showed that YBS1 administration inhibited the initial development of adipocytes via stimulation of the p38 MAPK signaling pathway, which in turn controlled PPARγ expression. In summary, YBS1 has potential efficacy as an anti-obesity supplement and requires further exploration.


Subject(s)
3T3-L1 Cells , Adipocytes , Adipogenesis , Cell Differentiation , Lactobacillus acidophilus , Obesity , PPAR gamma , Signal Transduction , p38 Mitogen-Activated Protein Kinases , PPAR gamma/metabolism , PPAR gamma/genetics , Animals , Mice , p38 Mitogen-Activated Protein Kinases/metabolism , Adipogenesis/drug effects , Adipocytes/drug effects , Adipocytes/metabolism , Cell Differentiation/drug effects , Signal Transduction/drug effects , Obesity/metabolism , Anti-Obesity Agents/pharmacology , Probiotics/pharmacology , Triglycerides/metabolism
8.
ACS Nano ; 18(21): 13635-13651, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38753978

ABSTRACT

As an escalating public health issue, obesity and overweight conditions are predispositions to various diseases and are exacerbated by concurrent chronic inflammation. Nonetheless, extant antiobesity pharmaceuticals (quercetin, capsaicin, catecholamine, etc.) manifest constrained efficacy alongside systemic toxic effects. Effective therapeutic approaches that selectively target adipose tissue, thereby enhancing local energy expenditure, surmounting the limitations of prevailing antiobesity modalities are highly expected. In this context, we developed a temperature-sensitive hydrogel loaded with recombinant high-density lipoprotein (rHDL) to achieve targeted delivery of resveratrol, an adipose browning activator, to adipose tissue. rHDL exhibits self-regulation on fat cell metabolism and demonstrates natural targeting toward scavenger receptor class B type I (SR-BI), which is highly expressed by fat cells, thereby achieving a synergistic effect for the treatment of obesity. Additionally, the dispersion of rHDL@Res in temperature-sensitive hydrogels, coupled with the regulation of their degradation and drug release rate, facilitated sustainable drug release at local adipose tissues over an extended period. Following 24 days' treatment regimen, obese mice exhibited improved metabolic status, resulting in a reduction of 68.2% of their inguinal white adipose tissue (ingWAT). Specifically, rHDL@Res/gel facilitated the conversion of fatty acids to phospholipids (PA, PC), expediting fat mobilization, mitigating triglyceride accumulation, and therefore facilitating adipose tissue reduction. Furthermore, rHDL@Res/gel demonstrated efficacy in attenuating obesity-induced inflammation and fostering angiogenesis in ingWAT. Collectively, this engineered local fat reduction platform demonstrated heightened effectiveness and safety through simultaneously targeting adipocytes, promoting WAT browning, regulating lipid metabolism, and controlling inflammation, showing promise for adipose-targeted therapy.


Subject(s)
Adipose Tissue , Lipoproteins, HDL , Animals , Mice , Lipoproteins, HDL/chemistry , Lipoproteins, HDL/metabolism , Adipose Tissue/metabolism , Recombinant Proteins , Resveratrol/pharmacology , Resveratrol/chemistry , Obesity/drug therapy , Obesity/metabolism , Hydrogels/chemistry , Mice, Inbred C57BL , Humans , Male , Anti-Obesity Agents/pharmacology , Anti-Obesity Agents/chemistry , Drug Delivery Systems , Scavenger Receptors, Class B/metabolism
9.
Food Res Int ; 187: 114427, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38763677

ABSTRACT

The scourge of obesity arising from obesogens and poor dieting still ravages our planet as half of the global population may be overweight and obese by 2035. This metabolic disorder is intertwined with type 2 diabetes (T2D), both of which warrant alternative therapeutic options other than clinically approved drugs like orlistat with their tendency of abuse and side effects. In this review, we comprehensively describe the global obesity problem and its connection to T2D. Obesity, overconsumption of fats, the mechanism of fat digestion, obesogenic gut microbiota, inhibition of fat digestion, and natural anti-obesity compounds are discussed. Similar discussions are made for diabetes with regard to glucose regulation, the diabetic gut microbiota, and insulinotropic compounds. The sources and production of anti-obesity bioactive peptides (AOBPs) and anti-diabetic bioactive peptides (ADBPs) are also described while explaining their structure-function relationships, gastrointestinal behaviors, and action mechanisms. Finally, the techno-functional applications of AOBPs and ADBPs are highlighted.


Subject(s)
Anti-Obesity Agents , Diabetes Mellitus, Type 2 , Gastrointestinal Microbiome , Hypoglycemic Agents , Obesity , Peptides , Humans , Obesity/drug therapy , Peptides/pharmacology , Peptides/therapeutic use , Anti-Obesity Agents/pharmacology , Hypoglycemic Agents/therapeutic use , Hypoglycemic Agents/pharmacology , Diabetes Mellitus, Type 2/drug therapy , Gastrointestinal Microbiome/drug effects , Animals
10.
Int J Biol Macromol ; 270(Pt 2): 132232, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38734349

ABSTRACT

High polymerization persimmon tannin has been reported to have lipid-lowering effects. Unfortunately, the poor solubility restricts its application. This research aimed to investigate the effect and mechanism of inulin on solubilizing of persimmon tannin. Furthermore, we examined whether the addition of inulin would affect the attenuated obesity effect of persimmon tannin. Transmission electron microscope (TEM), Isothermal titration calorimetry (ITC) and Fourier transform infrared spectroscopy (FT-IR) results demonstrated that inulin formed a gel-like network structure, which enabled the encapsulation of persimmon tannin through hydrophobic and hydrogen bond interactions, thereby inhibiting the self-aggregation of persimmon tannin. The turbidity of the persimmon tannin solution decreased by 56.2 %, while the polyphenol content in the supernatant increased by 60.0 %. Furthermore, biochemical analysis and 16s rRNA gene sequencing technology demonstrated that persimmon tannin had a significant anti-obesity effect and improved intestinal health in HFD-fed mice. Moreover, inulin was found to have a positive effect on enhancing the health benefits of persimmon tannin, including improving hepatic steatosis and gut microbiota dysbiosis. it enhanced the abundance of beneficial core microbes while decreasing the abundance of harmful bacteria. Our findings expand the applications of persimmon tannin in the food and medical sectors.


Subject(s)
Anti-Obesity Agents , Gastrointestinal Microbiome , Inulin , Obesity , Solubility , Tannins , Inulin/chemistry , Inulin/pharmacology , Tannins/chemistry , Tannins/pharmacology , Animals , Mice , Anti-Obesity Agents/pharmacology , Anti-Obesity Agents/chemistry , Gastrointestinal Microbiome/drug effects , Obesity/drug therapy , Polymerization , Diospyros/chemistry , Male , Diet, High-Fat/adverse effects , Polyphenols/chemistry , Polyphenols/pharmacology
11.
J Appl Microbiol ; 135(5)2024 May 01.
Article in English | MEDLINE | ID: mdl-38740521

ABSTRACT

AIMS: The aim of this study was to evaluate the antiobesity effects of heat-killed Lactiplantibacillus plantarum Shinshu N-07 (N-07) isolated from fermented Brassica rapa L. METHODS AND RESULTS: Male mice were divided into three groups (n = 10/group); normal diet, western diet (WD), or WD + N-07 (N-07) group and administered each diet for 56 days. The N-07 group showed significant suppression of body weight gain and epididymal fat, perirenal fat, and liver weights compared with the WD group. Higher levels of fecal total cholesterol, triglyceride (TG), and free fatty acid (FFA) were observed in the N-07 group than in the WD group. The mRNA expression of the cholesterol transporter ATP-binding cassette transporter G5 (ABCG5) was significantly increased in the small intestine of N-07-fed mice compared with WD-fed mice. Moreover, N-07 supplementation significantly increased the mRNA expression of ABCG5 and ABCG8 in Caco-2 cells. Furthermore, the TG- and FFA-removal ability of N-07 was confirmed to evaluate its soybean oil- and oleic acid-binding capacities in in vitro experiments. CONCLUSIONS: The antiobesity effects of N-07 might be due to its ability to promote lipid excretion by regulating cholesterol transporter expression and lipid-binding ability.


Subject(s)
Diet, Western , Obesity , Animals , Male , Mice , Obesity/metabolism , Humans , ATP Binding Cassette Transporter, Subfamily G, Member 5/genetics , ATP Binding Cassette Transporter, Subfamily G, Member 5/metabolism , Anti-Obesity Agents/pharmacology , Lactobacillus plantarum , Mice, Obese , ATP Binding Cassette Transporter, Subfamily G, Member 8/genetics , ATP Binding Cassette Transporter, Subfamily G, Member 8/metabolism , Cholesterol/metabolism , Probiotics , Caco-2 Cells , Brassica rapa/chemistry , Hot Temperature , Lipoproteins/metabolism , Triglycerides/metabolism , Liver/metabolism , Mice, Inbred C57BL
12.
Food Chem ; 448: 139140, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38574720

ABSTRACT

Theabrownins (TBs) are heterogeneous mixtures of water-soluble brown tea pigments, and important constituents to evaluate the quality of dark tea. TBs have numerous hydroxyl and carboxyl groups and are formed by the oxidative polymerization of tea polyphenols. Many biological activities attributed to TBs, including antioxidant, anti-obesity, and lipid-regulating, have been demonstrated. This review summarizes the research progress made on the formation mechanism and physicochemical properties of TBs. It also discusses their protective effects against various diseases and associated potential molecular mechanisms. Additionally, it examines the signaling pathways mediating the bioactivities of TBs and highlights the difficulties and challenges of TBs research as well as their research prospects and applications.


Subject(s)
Antioxidants , Humans , Antioxidants/chemistry , Animals , Camellia sinensis/chemistry , Tea/chemistry , Polyphenols/chemistry , Polyphenols/pharmacology , Plant Extracts/chemistry , Plant Extracts/pharmacology , Catechin/chemistry , Anti-Obesity Agents/chemistry , Anti-Obesity Agents/pharmacology
13.
Int J Mol Sci ; 25(8)2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38674060

ABSTRACT

Mandarin peel, a main by-product from the processing of citrus juice, has been highlighted for its various bioactivities and functional ingredients. Our previous study proved the inhibitory effects of Celluclast extract from mandarin peel (MPCE) on lipid accumulation and differentiation in 3T3-L1 adipocytes. Therefore, the current study aimed to evaluate the anti-obesity effect of MPCE in high-fat diet (HFD)-induced obese mice. The high-performance liquid chromatography (HPLC) analysis exhibited that narirutin and hesperidin are the main active components of MPCE. Our current results showed that MPCE supplementation decreased adiposity by reducing body and organ weights in HFD-induced obese mice. MPCE also reduced triglyceride (TG), alanine transaminase (ALT), aspartate transaminase (AST), and leptin contents in the serum of HFD-fed mice. Moreover, MPCE significantly inhibited hepatic lipid accumulation by regulating the expression levels of proteins associated with lipid metabolism, including sterol regulatory element-binding protein (SREBP1c), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC). Furthermore, MPCE administration significantly inhibited both adipogenesis and lipogenesis, with modulation of energy metabolism by activating 5' adenosine monophosphate-activated protein kinase (AMPK) and lipolytic enzymes such as hormone-sensitive lipase (HSL) in the white adipose tissue (WAT). Altogether, our findings indicate that MPCE improves HFD-induced obesity and can be used as a curative agent in pharmaceuticals and nutraceuticals to alleviate obesity and related disorders.


Subject(s)
Adipogenesis , Citrus , Diet, High-Fat , Disaccharides , Energy Metabolism , Flavanones , Mice, Inbred C57BL , Obesity , Plant Extracts , Animals , Diet, High-Fat/adverse effects , Obesity/metabolism , Obesity/drug therapy , Obesity/etiology , Citrus/chemistry , Mice , Energy Metabolism/drug effects , Plant Extracts/pharmacology , Male , Adipogenesis/drug effects , Lipid Metabolism/drug effects , 3T3-L1 Cells , Anti-Obesity Agents/pharmacology , Liver/metabolism , Liver/drug effects , Lipogenesis/drug effects , Triglycerides/metabolism , Triglycerides/blood
14.
Biosci Rep ; 44(4)2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38577975

ABSTRACT

Since 1975, the incidence of obesity has increased to epidemic proportions, and the number of patients with obesity has quadrupled. Obesity is a major risk factor for developing other serious diseases, such as type 2 diabetes mellitus, hypertension, and cardiovascular diseases. Recent epidemiologic studies have defined obesity as a risk factor for the development of neurodegenerative diseases, such as Alzheimer's disease (AD) and other types of dementia. Despite all these serious comorbidities associated with obesity, there is still a lack of effective antiobesity treatment. Promising candidates for the treatment of obesity are anorexigenic neuropeptides, which are peptides produced by neurons in brain areas implicated in food intake regulation, such as the hypothalamus or the brainstem. These peptides efficiently reduce food intake and body weight. Moreover, because of the proven interconnection between obesity and the risk of developing AD, the potential neuroprotective effects of these two agents in animal models of neurodegeneration have been examined. The objective of this review was to explore anorexigenic neuropeptides produced and acting within the brain, emphasizing their potential not only for the treatment of obesity but also for the treatment of neurodegenerative disorders.


Subject(s)
Anti-Obesity Agents , Neuropeptides , Neuroprotective Agents , Obesity , Humans , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Animals , Obesity/drug therapy , Obesity/metabolism , Neuropeptides/metabolism , Neuropeptides/pharmacology , Neuropeptides/therapeutic use , Anti-Obesity Agents/pharmacology , Anti-Obesity Agents/therapeutic use , Neurodegenerative Diseases/drug therapy , Neurodegenerative Diseases/metabolism , Neurodegenerative Diseases/prevention & control , Hypothalamus/drug effects , Hypothalamus/metabolism , Hypothalamus/pathology , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Alzheimer Disease/prevention & control , Brain/drug effects , Brain/metabolism , Brain/pathology , Eating/drug effects
15.
PLoS One ; 19(4): e0300544, 2024.
Article in English | MEDLINE | ID: mdl-38656972

ABSTRACT

Obesity is a major global health epidemic that has adverse effects on both the people affected as well as the cost to society. Several anti-obesity drugs that target GLP-1 receptors have recently come to the market. Here, we describe the effects of tesofensine, a novel anti-obesity drug that acts as a triple monoamine neurotransmitter reuptake inhibitor. Using various techniques, we investigated its effects on weight loss and underlying neuronal mechanisms in mice and rats. These include behavioral tasks, DeepLabCut videotaped analysis, electrophysiological ensemble recordings, optogenetic activation, and chemogenetic silencing of GABAergic neurons in the Lateral Hypothalamus (LH). We found that tesofensine induces a greater weight loss in obese rats than lean rats, while differentially modulating the neuronal ensembles and population activity in LH. In Vgat-ChR2 and Vgat-IRES-cre transgenic mice, we found for the first time that tesofensine inhibited a subset of LH GABAergic neurons, reducing their ability to promote feeding behavior, and chemogenetically silencing them enhanced tesofensine's food-suppressing effects. Unlike phentermine, a dopaminergic appetite suppressant, tesofensine causes few, if any, head-weaving stereotypy at therapeutic doses. Most importantly, we found that tesofensine prolonged the weight loss induced by 5-HTP, a serotonin precursor, and blocked the body weight rebound that often occurs after weight loss. Behavioral studies on rats with the tastant sucrose indicated that tesofensine's appetite suppressant effects are independent of taste aversion and do not directly affect the perception of sweetness or palatability of sucrose. In summary, our data provide new insights into the effects of tesofensine on weight loss and the underlying neuronal mechanisms, suggesting that tesofensine may be an effective treatment for obesity and that it may be a valuable adjunct to other appetite suppressants to prevent body weight rebound.


Subject(s)
Anti-Obesity Agents , Bridged Bicyclo Compounds, Heterocyclic , GABAergic Neurons , Obesity , Animals , GABAergic Neurons/drug effects , GABAergic Neurons/metabolism , Rats , Mice , Anti-Obesity Agents/pharmacology , Male , Obesity/drug therapy , Obesity/metabolism , Feeding Behavior/drug effects , Hypothalamic Area, Lateral/drug effects , Hypothalamic Area, Lateral/metabolism , Hypothalamus/drug effects , Hypothalamus/metabolism , Mice, Transgenic , Weight Loss/drug effects , Rats, Sprague-Dawley
16.
J Food Sci ; 89(5): 3094-3109, 2024 May.
Article in English | MEDLINE | ID: mdl-38634238

ABSTRACT

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


Subject(s)
3T3-L1 Cells , Anti-Obesity Agents , Fermentation , Moringa oleifera , Obesity , Phenols , Plant Leaves , Tea , Volatile Organic Compounds , Animals , Mice , Moringa oleifera/chemistry , Plant Leaves/chemistry , Phenols/analysis , Phenols/pharmacology , Anti-Obesity Agents/pharmacology , Tea/chemistry , Volatile Organic Compounds/analysis , Volatile Organic Compounds/pharmacology , Male , Plant Extracts/pharmacology , Mice, Inbred C57BL , Polyphenols/pharmacology , Polyphenols/analysis , PPAR gamma/metabolism
17.
Food Funct ; 15(10): 5300-5314, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38669145

ABSTRACT

Growing research has highlighted that the consumption of dairy products improves the metabolic health in obese individuals by functioning as regulatory modulators. However, the molecular basis of this effect remains largely unknown. Herein, we report a dairy-derived peptide, which we named Miltin, that activates the thermogenesis of brown adipocytes and increases white adipocyte browning. Previously, Miltin was merely identified for its antioxidant capacity, although it is commonly present in different dairy products. In this study, we revealed the effect of Miltin in modulating adipose thermogenesis and further explored its potential in treating obesity through in vivo and in vitro strategies. The administration of Miltin in mice fed with a high-fat diet resulted in enhanced thermogenesis, improved glucose homeostasis, and reduced body mass and lipid accumulation, indicating the anti-obesity effect of Miltin. Genomic analysis revealed that Miltin modulates thermogenesis by inducing the activation of the MAPK signaling pathway by preferentially interacting with GADD45γ to promote its stability. Together, our findings indicate that Miltin's role in initiating the thermogenesis of adipocytes makes it a potential anti-obesity therapy for future development.


Subject(s)
Anti-Obesity Agents , Mice, Inbred C57BL , Obesity , Thermogenesis , Animals , Thermogenesis/drug effects , Mice , Anti-Obesity Agents/pharmacology , Obesity/drug therapy , Obesity/metabolism , Male , Diet, High-Fat , 3T3-L1 Cells , Adipocytes, Brown/drug effects , Adipocytes, Brown/metabolism , Peptides/pharmacology , Adipocytes/drug effects , Adipocytes/metabolism , Humans
18.
Expert Opin Pharmacother ; 25(5): 611-619, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38629387

ABSTRACT

INTRODUCTION: Semaglutide, a glucagon-like peptide-1 receptor agonist, is associated with significant weight loss, yet its impact on lean body mass remains insufficiently understood. This review investigates the effect of semaglutide on lean mass in the context of obesity management. METHODOLOGY: This study investigates through different databases (PubMed, Elsevier, and Google Scholar) from 2016 for randomized control trials (RCTs) or observational studies that assessed the use of semaglutide in overweight or obese patients, regardless of whether they have type 2 diabetes or not. The studies compared semaglutide to a placebo or alternative medications. RESULTS: Six studies with 1,541 overweight or obese adults were included, and significant weight reductions were observed primarily due to fat mass loss. While the lean mass remained stable in some cases, notable reductions ranging from almost 0% to 40% of total weight reduction were observed in others. Noteworthy decreases in lean mass were particularly evident in larger trials, yet the proportion of lean mass relative to total body mass increased, suggesting a positive overall outcome. CONCLUSION: Semaglutide displays potential for weight loss primarily through fat mass reduction. However, concerns arise from notable reductions in lean mass, especially in trials with a larger number of patients.


Subject(s)
Glucagon-Like Peptides , Obesity , Overweight , Randomized Controlled Trials as Topic , Weight Loss , Humans , Glucagon-Like Peptides/therapeutic use , Glucagon-Like Peptides/pharmacology , Weight Loss/drug effects , Obesity/drug therapy , Overweight/drug therapy , Glucagon-Like Peptide-1 Receptor/agonists , Anti-Obesity Agents/therapeutic use , Anti-Obesity Agents/pharmacology , Diabetes Mellitus, Type 2/drug therapy
19.
Int J Food Sci Nutr ; 75(4): 426-435, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38557440

ABSTRACT

This randomised, placebo-controlled, double-blind, parallel-group study aimed to determine whether encapsulated Ashitaba chalcone (16 mg comprising 10.1 mg 4-hydroxyderricin and 5.9 mg xanthoangelol) could reduce obesity in 17 men and 25 women with a body mass index (BMI) of 25 to < 30. Participants ingested capsules containing either the chalcone or a placebo daily for 12 weeks. The primary endpoint was changes in visceral fat areas determined by computed tomography (CT) at baseline, and at 8 and 12 weeks later. The primary endpoint, abdominal visceral fat area, was significantly reduced in the chalcone, compared with a placebo group 12 weeks after screening (p < 0.05). The secondary endpoint, waist circumference, was significantly decreased in the chalcone, compared with the placebo group at weeks 8 and 12 (p < 0.05 at week 8; p < 0.01 at week 12). Therefore, Ashitaba chalcone has anti-obesity benefits for overweight men and women.


Subject(s)
Chalcone , Intra-Abdominal Fat , Overweight , Waist Circumference , Humans , Male , Female , Double-Blind Method , Adult , Middle Aged , Intra-Abdominal Fat/drug effects , Chalcone/analogs & derivatives , Chalcone/pharmacology , Body Mass Index , Obesity , Anti-Obesity Agents/pharmacology
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