Search Results (2,762)

Obesity is a major global health concern associated with increased risks of chronic diseases and mortality. Inhibiting pancreatic lipase, a key enzyme in dietary fat absorption, presents a promising therapeutic approach. This study aimed to evaluate the inhibitory potential of piperidine derivatives (1 and 2) and pyrrolidine derivatives (3–13) against pancreatic lipase (PL) through both enzymatic assays and molecular docking simulations. Among the tested compounds, compound 12 demonstrated the highest PL inhibitory activity with IC₅₀ 0.143 ± 0.001 mg/mL and the strongest binding energy (−8.24 kcal/mol), attributed to extensive hydrogen bonding with Gly76, Phe77, Asp79, and His151. Compounds 10 and 13 also exhibited notable inhibitory activity, attributed to their extensive hydrogen bond network with residues Gly76, Phe77, Asp79, and His151. Particularly the presence and position of hydroxy and carbonyl groups and the length of alkyl side chains critically influenced binding stability and specificity. These findings demonstrate that specific structural modifications in pyrrolidine derivatives significantly affect pancreatic lipase inhibition. Compound 12, with its optimal molecular architecture and interaction profile, stands out as the most promising candidate for further development as an anti-obesity agent, with compounds 10 and 13 offering additional scaffolds for future optimization. Full article

Resveratrol (RVT) is a plant-derived polyphenol found in traditional medicinal species such as Veratrum grandiflorum and Polygonum cuspidatum, known for their bioactive secondary metabolites. This study evaluates the anti-obesity effects of RVT alone and in combination with orlistat (OLT), a pharmaceutical lipase inhibitor, in a high-fat diet-induced obesity model in rats. Female Sprague-Dawley rats were assigned to receive RVT, OLT, a combination of both, or no treatment, over a four-week period. The combination of RVT and OLT led to a significant reduction in body weight gain and improvement in lipid profiles, including decreased LDL cholesterol. Additionally, the combination ameliorated liver enzyme elevations associated with obesity-related hepatic stress. These findings demonstrate that resveratrol potentiates orlistat’s pharmacological efficacy and highlights the therapeutic potential of bioactive compounds from medicinal plants in metabolic disease management. This study supports further development of plant-based pharmacological agents and synergistic formulations for the treatment of obesity and associated comorbidities. Full article

Background: Obesity, characterized by an abnormal and excessive accumulation of fat, significantly affects health by increasing the probability of chronic diseases and has become a pressing global health issue. Among natural compounds with therapeutic potential, rutin exhibits diverse biological effects, such as antioxidant, anti-inflammatory, and hypolipidemic properties. Objective: The purpose of this work is to evaluate the preventive effects of rutin loaded on chitosan nanoparticles on metabolic and oxidative alterations in male albino rats fed a high-fat diet (HFD). Method: The rats were allocated to four distinct groups: control, HFD, HFD treated with 50 mg/kg rutin, and HFD treated with 50 mg/kg nano-rutin, respectively, for six weeks. Results: Molecular docking analysis revealed that rutin exhibits an inhibitory interaction with PPAR-γ, suggesting its potential role in suppressing adipogenesis and contributing to its preventive effect against obesity. Nano-rutin markedly improved glycemic control, reducing fasting glucose from 161.75 ± 8.37 mg/dL in the HFD group to 133.50 ± 3.55 mg/dL, compared to 92.17 ± 3.53 mg/dL in controls. Serum leptin levels decreased from 28.95 ± 1.06 ng/mL in the HFD group to 15.58 ± 0.65 ng/mL with nano-rutin, approaching the control value of 10.43 ± 0.80 ng/mL. Oxidative stress was also significantly alleviated, as shown by a reduction in malondialdehyde (MDA) from 8.43 ± 0.20 U/µL in HFD rats to 6.57 ± 0.08 U/µL with nano-rutin, versus 1.29 ± 0.13 U/µL in controls. Conclusions: Rutin loaded on chitosan nanoparticles demonstrated protective effects against high-fat diet-induced obesity, mainly through modulation of leptin signaling and oxidative stress pathways. These findings highlight the promise of nano-rutin as a natural agent for preventing metabolic disorders related to obesity. Full article

Metabolic syndrome refers to a group of conditions that commonly occur together, including abdominal obesity, high blood pressure, elevated blood sugar, high triglyceride levels, and low high-density lipoprotein cholesterol (HDL). These factors collectively increase the risk of cardiovascular disease, diabetes, and cognitive impairment. Recent research has identified a connection between metabolic syndrome and cognitive disorders such as mild cognitive impairment and vascular dementia (VaD). Mulberry (Morus alba L.) is a natural source of bioactive compounds with antioxidant, anti-inflammatory, and lipid-regulating properties. This meta-analysis assessed the potential of mulberry extract as an adjunctive treatment for metabolic risk factors linked to vascular dementia. We systematically reviewed randomized controlled trials (RCTs) published up to May 2025 that compared mulberry extract to placebo or standard care in adults with metabolic disorders. Fifteen trials including 1202 participants met the inclusion criteria. The primary outcomes were fasting glucose, fasting insulin, liver enzyme levels, lipid profiles, and inflammatory markers such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hs-CRP). The pooled results indicated that mulberry supplementation improved blood sugar control and lowered total cholesterol, low-density lipoprotein cholesterol (LDL), triglycerides, fasting blood glucose, glycosylated hemoglobin (HbA1c), homeostasis model assessment for insulin resistance (HOMA-IR), and inflammatory markers. Aspartate aminotransferase (AST) improved, whereas alanine aminotransferase (ALT) showed no significant change. Subgroup analyses revealed that greater benefits were associated with shorter treatment durations and doses below 500 milligrams per day. Furthermore, extracts from different parts of the mulberry plant showed varying effects on lipid and glucose metabolism. None of the included trials directly measured cognitive or neurovascular outcomes, so any potential neurovascular protection is inferred from changes in metabolic and inflammatory markers rather than demonstrated. In summary, these findings suggest that mulberry extract may be a promising complementary approach for managing metabolic risk factors in people at risk for VaD. However, further large-scale and rigorously designed studies are required to confirm its clinical benefits and to identify the most effective preparations. Full article

The increasing prevalence of obesity, a chronic disease, necessitates the development and evaluation of evidence-based prevention and intervention strategies tailored to heterogeneous populations. Certain fruits, including papaya and pineapple (Ananas comosus), have been investigated as potential dietary components in obesity management. In the context of obesity and chronic low-grade inflammation, bromelain, a proteolytic enzyme derived from pineapple, is a widely studied phytotherapeutic agent that acts through multiple mechanisms intersecting immune and metabolic pathways. This narrative review summarizes current evidence on the effects of bromelain in obesity, low-grade inflammation, and related metabolic disturbances. Searches of the literature were conducted in Google Scholar, PubMed, and Scopus databases. This review incorporates findings from in vitro, animal, and human studies. We outline the mechanisms and evidence supporting the therapeutic efficacy of bromelain, emphasizing its implications for obesity management in clinical settings. Bromelain has been shown to exert significant anti-inflammatory activity and may modulate adipocyte metabolism, potentially alleviating comorbidities associated with excess adiposity. Although its effects on immune cells are relatively well described, the mechanisms underlying bromelain’s actions on adipocytes remain incompletely understood. Full article

Pea peptides (PPs), as organic compounds, exhibit a variety of biological functions that make them useful for both the prevention and treatment of metabolic disorders. This study focused on how PPs modified by steam explosion (SE-PP) may help to treat mice with high-fat diet (HFD)-mediated glucose metabolism disorders. The experimental results indicate that both the 100 mg/kg BW SE-PP (SE-PPL group) and 400 mg/kg BW SE-PP (SE-PPH group) experienced substantial decreases in body weight, epididymal and inguinal fat mass, and blood glucose levels of obese mice (notably, the body weight of the SE-PPH group was decreased by 33.13% when compared with that of the HFD group (p < 0.05)). By stimulating the IRS-1/PI3K/AKT signaling system, SE-PP controlled glucose metabolism disorder in adipose tissue, while also inhibiting the TLR4/MYD88/NF-κB pathway to reduce inflammation. Furthermore, SE-PP restored the diversity of the gut microbiota destroyed by HFD. SE-PPH increased the Bacteroidetes/Firmicutes ratio from 0.042 to 0.26 (p < 0.05), which is a key indicator of microbiota balance. In addition, SE-PP enhanced the synthesis of short-chain fatty acids (SCFAs) such as isovalerate, propionate, and acetate, which are essential for maintaining intestinal homeostasis and improving metabolic health (supplementation of SE-PPH increased the levels of total SCFAs by 49.87% in obese mice (p < 0.05)). Full article

Obesity is an epidemic that currently impacts many nations. The persistence of this disease is shaped by both genetic and epigenetic factors that extend beyond calorie balance. Research in the past year has revealed that epigenetic and cellular memory within adipose tissue can predispose individuals to weight regain after initial fat loss, as shown by studies indicating persistent transcriptional and chromatin changes even after fat mass reduction. Independent studies also demonstrate long-lasting metabolic shifts, such as those triggered by glucose-dependent insulinotropic polypeptide receptor (GIPR)-induced thermogenesis and sarcolipin (SLN) stabilization that also support a form of “metabolic memory” that is associated with sustained weight loss. At the neural level, rare variants in synaptic genes like BSN (Bassoon presynaptic cytomatrix protein), a presynaptic scaffold protein, and APBA1 (amyloid beta precursor protein binding family A member 1), a neuronal adaptor involved in vesicular trafficking, disrupt communication in feeding circuits, elevating obesity risk and illustrating how synaptic integrity influences food intake regulation. Similarly, the spatial compartmentalization of metabolic signaling within neuronal cilia is emerging as crucial, with cilia-localized receptors G protein-coupled receptor 75 (GPR75) and G protein-coupled receptor 45 (GPR45) exerting opposing effects on energy balance and satiety. Meanwhile, genome-wide association studies (GWAS) have advanced through larger, more diverse cohorts and better integration of environmental and biological data. These studies have identified novel obesity-related loci and demonstrated the value of polygenic risk scores (PRS) in predicting treatment responses. For example, genetic variants in GLP-1R (glucagon-like peptide-1 receptor) and GIPR (glucose-dependent insulinotropic polypeptide receptor) may modulate the effectiveness of incretin-based therapies, while PRS for satiation can help match individuals to the most appropriate anti-obesity medications. This review focuses on studies in the last two years that highlight how advances in obesity genetics are driving a shift toward more personalized and mechanism-based treatment strategies. Full article

Estrogen-dependent conditions, such as endometriosis, adenomyosis, lipedema, polycystic ovary syndrome, and breast cancer, are intimately involved with hormonal changes related to estrogen and their receptors. These conditions can be expressed mainly during hormonal changes such as pregnancy, puberty, and menopause. They are associated with alterations in estrogen function and inflammatory mechanisms, leading to significant discomfort and a marked decrease in self-esteem in women. Resveratrol has been studied in the treatment of inflammatory diseases like obesity, metabolic syndrome, and endometriosis. The research suggests potential pathways through which resveratrol may also be beneficial in treating metabolic and estrogen-dependent conditions. We reviewed 63 articles from 2000 to 2025, prioritizing systematic reviews, meta-analyses, and randomized controlled trials in the PubMed, ScienceDirect, and SciELO databases. Our results suggest that resveratrol may benefit metabolic and estrogen-dependent conditions by modulating anti-inflammatory factors that regulate estrogen receptor activity, increasing lipolysis, decreasing insulin resistance, and mitigating oxidative stress. Future research should evaluate the long-term safety and potential therapeutic effects of resveratrol in metabolic conditions. Full article

Olive oil, a cornerstone of the Mediterranean diet, is increasingly recognized not only for its cardiovascular benefits but also for its potential role in cancer prevention and therapy. Among its bioactive constituents, several phenolic compounds—tyrosol, hydroxytyrosol, oleuropein, oleacein, and oleocanthal—have demonstrated promising anticancer activities in various experimental models. These compounds act synergistically through diverse mechanisms, including antioxidant, anti-inflammatory, and immunomodulatory effects, as well as modulation of cell proliferation, apoptosis, angiogenesis, and metastasis. Notably, oleocanthal selectively induces cancer cell death via lysosomal membrane permeabilization, while hydroxytyrosol and oleuropein exhibit potent radical-scavenging and anti-proliferative properties. This review synthesizes findings from in vitro, in vivo, and clinical studies on the anticancer potential of these polyphenols, with emphasis on their mechanisms of action and possible applications in cancer prevention and adjunctive therapy. Given the established link between obesity and cancer development, clinical studies examining the metabolic, anti-inflammatory, and immunomodulatory effects of olive polyphenols in populations with obesity or prediabetes provide valuable insights into their potential to influence cancer-related pathways indirectly. However, direct clinical evidence in cancer patients remains limited and preliminary, underscoring the need for focused, well-controlled trials with cancer-specific endpoints. Furthermore, it critically evaluates the translational relevance of these findings, highlighting gaps in clinical research and future directions. Literature was retrieved from Google Scholar, PubMed, and ScienceDirect using keywords such as cancer, immunomodulatory, anti-inflammatory, olive, tyrosol, hydroxytyrosol, oleuropein, oleacein, and oleocanthal. Given the rising global cancer burden and the favorable safety profiles of these natural molecules, elucidating their molecular actions may support the development of novel integrative therapeutic strategies. Full article

Background/Objectives: Obesity is a chronic metabolic disorder characterized by the excessive expansion of adipose tissue and impaired energy homeostasis. Natural products, such as plant extracts, are gaining attention as potential anti-obesity agents. This study aimed to evaluate and compare the anti-obesity effects of ginger (Zingiber officinale Roscoe) extract alone and as a mixture with long pepper (Piper longum L.) extract in a mouse model of high-fat diet-induced obesity. Methods: Male ICR mice were fed a high-fat diet to induce obesity and were orally administered ginger extract (60 mg/kg/day) or a 1:1 mixture of ginger and long pepper extracts (30 mg/kg/day each) for 8 weeks. Body weight, fat mass, glucose tolerance, and serum lipid levels were measured. Results: Ginger extract alone significantly reduced body weight gain and visceral and subcutaneous fat accumulation and improved glucose homeostasis and serum lipid profiles compared to the high-fat diet group. These effects were more pronounced than those observed with the mixture group. Ginger extract upregulated lipolytic markers via activation of the protein kinase A (PKA) signaling pathway and increased expression of uncoupling protein 1 (UCP1), indicating browning of white adipose tissue. Conclusions: Ginger extract alone exhibited significant anti-obesity effects compared to the mixture with long pepper extract. These findings suggest that ginger extract may serve as a promising natural agent for the prevention and management of obesity-related metabolic dysfunction. Full article

With the growing use of anti-obesity medications (AOMs), particularly glucagon-like peptide-1 (GLP-1) receptor agonists, interest in their impact on chemosensory function has increased. We report a case of subjective olfactory discomfort that developed during AOM therapy despite normal objective test results. A 41-year-old woman received the GLP-1 receptor agonist semaglutide for 24 weeks. Thorough olfactory function evaluation was performed using the Questionnaire of Olfactory Disorders (a validated questionnaire), the Yonsei Olfactory Function Test (for psychophysical testing), and chemical gustometry. The tests were performed before treatment and after 24 weeks of AOM therapy. At baseline, the patient had no olfactory complaints and showed normal test results. After treatment, she reported significant subjective olfactory discomfort (visual analog scale score: 48, maximum: 50), with decreased quality of life and parosmia, despite stable Yonsei Olfactory Function scores and normal gustatory function. This case highlights the possible mismatch between subjective and objective olfactory assessment during AOM therapy. Comprehensive chemosensory evaluations and interdisciplinary collaboration are essential, and further large-scale long-term studies are required. Full article

Background/Objectives: Gestational diabetes (GD) is a common pregnancy complication linked to inflammation. Obesity, a major risk factor, is associated with elevated pro-inflammatory markers (TNF-α, IL-6) and reduced anti-inflammatory IL-10 and adiponectin. This study investigated the role of inflammatory factors (IL-6, TNF-α, IL-10, adiponectin) and their genetic variants (rs1800629, rs1800796, rs1800896, rs266729) in a unique four-group study design of pregnant women. Methods: We collected venous blood from 162 women in the third trimester of pregnancy. We measured IL-6, IL-10, TNF-α, and adiponectin levels and performed real-time PCR genotyping for the selected SNPs. Results: IL-6 levels were significantly higher (p < 0.001) in pregnant women with GD and additional complications. The IL-6 SNP rs1800796 heterozygous CG genotype showed a slightly increased GD risk (OR = 1.41). However, we found no significant associations between GD and TNF-α rs1800629 or IL-10 rs1800896 SNPs. The AdipoQ rs266729 homozygous CC genotype was linked to increased GD risk (p = 0.03 for superdominant model). Importantly, no significant correlations were observed between inflammatory marker levels and gene variants within any study group. Conclusions: Our findings suggest a greater inflammatory burden in GD pregnancies with additional complications. While certain IL-6 and AdipoQ variants might contribute to GD risk, the overall weak association between inflammatory markers and gene variants likely reflects the complex polygenic nature of GD, environmental factors, or the study’s sample size. Full article

Interferon regulatory factor 5 (IRF5) plays a pivotal role in innate immune responses and macrophage polarization. Although its role in obesity-associated inflammation has been described, sex-specific differences in adipose IRF5 expression and its association with immune and metabolic markers remain poorly defined. To evaluate sex-specific associations between adipose tissue (AT) IRF5 expression and key inflammatory and metabolic markers in overweight and obese individuals. Subcutaneous AT samples from overweight/obese male and female subjects were analyzed for IRF5 expression using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Correlation and multiple linear regression analyses were performed to identify its associations with inflammatory gene expression and metabolic parameters including insulin, glucose, HOMA-IR, and adipokines. RF5 gene and protein levels were significantly elevated in the AT of overweight/obese females compared to males (p < 0.0001), with expression increasing progressively with BMI in females but not in males. Despite these sex-dependent expression levels, IRF5 demonstrated consistent, sex-independent positive correlations with several core immune and inflammatory markers, including CCR5, CD11c, CD16, CD163, FOXP3, RUNX1, and MyD88. However, distinct sex-specific patterns emerged: in males, IRF5 correlated positively with classical pro-inflammatory markers such as IL-2, IL-6, IL-8, TNF-α, and IRAK1; whereas in females, IRF5 was associated with a broader array of immune markers, including chemokines (CCL7, CXCL11), pattern recognition receptors (TLR2, TLR8, TLR9), and macrophage markers (CD68, CD86), along with anti-inflammatory mediators such as IL-10 and IRF4. Notably, IRF5 expression in overweight/obese males, but not females, was significantly associated with metabolic dysfunction, showing positive correlations with fasting blood glucose, HbA1c, insulin, and homeostatic model assessment for insulin resistance (HOMA-IR) levels. Multiple regression analyses revealed sex-specific predictors of IRF5 expression, with metabolic (HOMA-IR) and inflammatory (IRAK1, MyD88) markers emerging in males, while immune-related genes (RUNX1, CD68, CCL7, MyD88) predominated in females. These findings underscore a sex-divergent role of IRF5 in AT, with implications for differential regulation of immune-metabolic pathways in obesity and its complications. Full article

Background: Pancreatic lipase (PL), the principal enzyme catalyzing the hydrolysis of dietary triacylglycerols in the intestinal lumen, is pivotal for efficient lipid absorption and plays a central role in metabolic homeostasis. Enhanced PL activity promotes excessive lipid assimilation and contributes to positive energy balance, key pathophysiological mechanisms underlying the escalating global prevalence of obesity—a complex, multifactorial condition strongly associated with metabolic disorders, including type 2 diabetes mellitus and cardiovascular disease. Inhibition of pancreatic lipase (PL) constitutes a well-established therapeutic approach for attenuating dietary lipid absorption and mitigating obesity. Methods: With the aim to identify putative PL inhibitors, a Structure-Based Virtual Screening (SBVS) of PhytoHub database naturally occurring derivatives was performed. A refined library of 10,404 phytochemicals was virtually screened against a crystal structure of pancreatic lipase. Candidates were filtered out based on binding affinity, Lipinski’s Rule of Five, and structural clustering, resulting in six lead compounds. Results: In vitro, enzymatic assays confirmed theoretical suggestions, highlighting Pinoresinol as the best PL inhibitor. Molecular dynamics simulations, performed to investigate the stability of protein–ligand complexes, revealed key interactions, such as persistent hydrogen bonding to catalytic residues. Conclusions: This integrative computational–experimental workflow highlighted new promising natural PL inhibitors, laying the foundation for future development of safe, plant-derived anti-obesity therapeutics. Full article

Sesame oil extraction byproduct (SOEB) contains a high percentage of protein (49.81 g/100 g), making it a suitable plant-based source for producing protein hydrolysates with nutraceutical potential. In this study, albumins, globulins, glutelins, and prolamins fractions were extracted and characterized from SOEB. These fractions were then enzymatically hydrolyzed with alcalase, yielding high soluble protein content (>90%) and hydrolysis degrees ranging from 34.66 to 45.10%. The hydrolysates were fractionated by molecular weight (<5 kDa, 3–5 kDa, 1–3 kDa, and <1 kDa). These fractions demonstrated potential for inhibiting the DPPH radical (25.19–95.79%) and the α-glucosidase enzyme (40.14–55.63%), particularly the fractions with molecular weight <1 kDa. We identified 28 peptides, with molecular weights between 332.20 and 1096.63 Da, which showed potent antioxidant activities (IC₅₀ = 90.18 µg/mL), as well as inhibitory effects on key enzymes such as α-glucosidase (IC₅₀ = 61.48 µg/mL), dipeptidyl peptidase IV (IC₅₀ = 12.12 µg/mL), and pancreatic lipase (IC₅₀ = 6.14 mg/mL). These results demonstrate the antioxidant, antihyperglycemic, antidiabetic, and anti-obesity potential of SOEB peptides, highlighting their use in the formulation of new functional foods or nutraceuticals. Full article