Search Results (2,336)

Objectives: Paratubal cysts (PTCs) are embryological remnants and are potentially hormonally responsive. Since hyperandrogenism (HA) is representative of polycystic ovary syndrome (PCOS), we examined whether biochemical hyperandrogenism is associated with PTCs in women with PCOS and if body mass index (BMI) and insulin resistance (IR) mediate this association. Methods: This retrospective study included 577 women diagnosed with PCOS at a tertiary academic center from 2010 to 2018. Clinical data included age at diagnosis, BMI, and diagnoses of hypertension, non-alcoholic fatty liver disease, and metabolic syndrome. Laboratory measures included total testosterone, sex hormone-binding globulin, anti-Müllerian hormone, luteinizing hormone, fasting glucose, insulin, and triglycerides (TG). Derived indices included a free androgen index (FAI), homeostasis model assessment of insulin resistance (HOMA-IR), and fasting glucose-to-insulin ratio. PTCs were identified through imaging or surgical findings. Structural equation modeling (SEM) assessed direct and indirect relationships between FAI, BMI, HOMA-IR, and PTCs, while adjusting for diagnostic age. Results: PTCs were identified in 2.77% of participants. BMI, FAI, TG, and IR indices were significantly higher for women with PTCs than those without PTCs. SEM revealed significant indirect effects of FAI on PTCs via BMI and HOMA-IR. The direct effect was negative, resulting in a non-significant total effect. A sensitivity model using HOMA-IR as the predictor showed a significant direct effect on PTCs without mediation via FAI. Conclusions: Biochemical HA may influence PTC development in PCOS through metabolic pathways, establishing the need to consider metabolic context when evaluating adnexal cysts in hyperandrogenic women. Full article

Insulin-regulated glucose uptake is a central mechanism in maintaining systemic glucose homeostasis, primarily occurring in skeletal muscle and adipose tissue. This process relies on the insulin-stimulated translocation of the glucose transporter, GLUT4, from specialized intracellular compartments, known as GLUT4 storage vesicles (GSVs), to the plasma membrane. Disruption of this pathway is a hallmark of insulin resistance and a key contributor to the pathogenesis of type 2 diabetes. Recent advances have provided critical insights into both the insulin signalling cascades and the complex biogenesis, as well as the trafficking and fusion dynamics of GSVs. This review synthesizes the current understanding of the molecular mechanisms governing GSV mobilization and membrane fusion, highlighting key regulatory nodes that may become dysfunctional in metabolic disease. By elucidating these pathways, we propose new therapeutic avenues targeting GSV trafficking to improve insulin sensitivity and combat type 2 diabetes. Full article

The kallikrein–kinin system and its B1 and B2 receptors are key regulators in metabolic disorders such as obesity, diabetes, and insulin resistance. Obesity, a chronic and multifactorial condition often associated with comorbidities like type 2 diabetes and dyslipidemia, remains poorly understood at the metabolic level. The kinin B2 receptor (B2R) is involved in blood pressure regulation and glucose metabolism, promoting glucose uptake in skeletal muscle via bradykinin. Studies in B2R-KO mice demonstrate that the absence of this receptor predisposes animals to glucose intolerance under a high-fat diet and impairs adaptive thermogenesis, indicating a protective role for B2R in metabolic homeostasis and insulin sensitivity. In contrast, the kinin B1 receptor (B1R) is inducible under pathological conditions and is activated by kinin metabolites. Mouse models lacking B1R exhibit improved metabolic profiles, including protection against high-fat diet-induced obesity and insulin resistance, enhanced energy expenditure, and increased leptin sensitivity. B1R inactivation in adipocytes enhances insulin responsiveness and glucose tolerance, supporting its role in the development of insulin resistance. Moreover, B1R deficiency improves energy metabolism and thermogenic responses to adrenergic and cold stimuli, promoting the activation of brown adipose tissue and the browning of white adipose tissue. Collectively, these findings suggest that B1R and B2R represent promising therapeutic targets for the treatment of metabolic disorders. Full article

Background and Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a progressive liver disorder associated with metabolic risk factors such as obesity, type 2 diabetes, and cardiovascular disease. If left untreated, the accumulation of excess hepatic fat can lead to inflammation, fibrosis, cirrhosis, hepatocellular carcinoma, and ultimately liver failure. Capsaicin (CAP), the primary pungent compound in chili peppers, has previously been shown to prevent weight gain in high-fat diet (HFD)-induced obesity models. In this study, we investigated the potential of dietary CAP to prevent HFD-induced MASLD. Methods: C57BL/6 mice were fed an HFD (60% kcal from fat) with or without 0.01% CAP supplementation for 26 weeks. We evaluated CAP’s effects on hepatic fat accumulation, inflammation, and mitochondrial function to determine its role in preventing MASLD. Results: CAP acts as a potent and selective agonist of the transient receptor potential vanilloid 1 (TRPV1) channel. We confirmed TRPV1 expression in the liver and demonstrated that CAP activates hepatic TRPV1, thereby preventing steatosis, improving insulin sensitivity, reducing inflammation, and enhancing fatty acid oxidation. These beneficial effects were observed in wild-type but not in TRPV1 knockout mice. Mechanistically, CAP-induced TRPV1 activation promotes calcium influx and activates AMPK, which leads to SIRT1-dependent upregulation of PPARα and PGC-1α, enhancing mitochondrial biogenesis and lipid metabolism. Conclusions: Our findings suggest that dietary CAP prevents MASLD through TRPV1 activation. TRPV1 signaling represents a promising therapeutic target for the prevention and management of MASLD in individuals with metabolic disorders. Full article

Insulin resistance (IR) plays a pivotal role in the pathogenesis of several dermatological diseases, including psoriasis, acne, acanthosis nigricans, and hidradenitis suppurativa (HS). These conditions are characterized by chronic inflammation, oxidative stress, and metabolic dysfunction, which are exacerbated by IR. This narrative review examines the emerging role of nutraceutical insulin-sensitizing agents (ISAs), including myo-inositol, alpha-lipoic acid, vitamin D, vitamin C, and folic acid, in managing IR-related dermatological disorders. A comprehensive literature search was conducted across Cochrane Library and MEDLINE (1965–May 2025), focusing on clinical trials involving nutraceutical ISAs in dermatological conditions associated with IR. Only human studies published in English were included. Evidence from randomized controlled trials (RCTs) and observational studies suggests that ISAs improve glycemic control, reduce oxidative stress, and modulate inflammatory pathways in IR-related dermatoses. Notably, myo-inositol combined with magnesium and folic acid has demonstrated significant reductions in acne severity, hirsutism, and quality-of-life impairments in women with polycystic ovary syndrome. Similar benefits have been observed in psoriasis and HS, though data remain limited. Nutraceutical ISAs offer a promising adjunctive approach for the management of IR-associated dermatological diseases, potentially addressing both metabolic dysfunction and skin inflammation. However, robust RCTs with long-term follow-up are needed to confirm these preliminary findings and to establish optimal treatment regimens. Full article

We recently reported that phospholipase A2 (PLA2)-mediated production of prostaglandins within the ventromedial hypothalamus (VMH) plays a critical role in systemic glucose homeostasis. However, the role of PLA2 in the VMH in regulating food intake is still unclear. Here, we attempted to investigate the role of PLA2 in regulating food intake and body weight in male mice. We injected an adeno-associated virus encoding short hairpin RNA (AAV-shRNA) targeting cytosolic phospholipase A2 (shPla2g4a) into the VMH. We assessed food intake, body weight, oxygen consumption, glucose tolerance, and insulin sensitivity. Three weeks after the AAV injection, the shPla2g4a group exhibited increased food intake and body weight gain compared to controls (shSCRM). Energy expenditure, oxygen consumption, and respiratory quotient (RQ) were comparable between groups. Our findings suggest that the cPLA2-mediated pathway in the VMH is critical for feeding behavior and maintaining energy homeostasis. Further investigation is needed to elucidate the underlying mechanisms. Full article

Adipose tissue inflammation contributes to obesity-induced insulin resistance. However, increasing evidence shows that high BMI (obesity) is not an accurate predictor of poor metabolic health in individuals. The molecular mechanisms regulating the metabolically activated M1 macrophage phenotype in the adipose tissues leading to insulin resistance remain largely unknown. Although the Janus Kinase (Jak)/signal transducer and activator of transcription 3 (Stat3) signaling in myeloid cells are known to promote the M2 phenotype in tumors, we demonstrate here that the Jak2/Stat3 pathway amplifies M1-mediated adipose tissue inflammation and insulin resistance under metabolic challenges. Ablating Jak2 in the myeloid compartment reduces insulin resistance in obese mice, which is associated with a decrease in infiltration of adipose tissue macrophages (ATMs). We show that the adoptive transfer of Jak2-deficient myeloid cells improves insulin sensitivity in obese mice. Furthermore, the protection of obese mice with myeloid-specific Stat3 deficiency against insulin resistance is also associated with reduced tissue infiltration by macrophages. Jak2/Stat3 in the macrophage is required for the production of pro-inflammatory cytokines that promote M1 macrophage polarization in the adipose tissues of obese mice. Moreover, free fatty acids (FFAs) activate Stat3 in macrophages, leading to the induction of M1 cytokines. Silencing the myeloid cell Stat3 with an in vivo siRNA targeted delivery approach reduces metabolically activated pro-inflammatory ATMs, thereby alleviating obesity-induced insulin resistance. These results demonstrate Jak2/Stat3 in myeloid cells is required for obesity-induced insulin resistance and inflammation. Moreover, targeting Stat3 in myeloid cells may be a novel approach to ameliorate obesity-induced insulin resistance. Full article

Background/Objectives: The effect of metformin on the secretory function of thyrotropic cells is sex-dependent. The current study aimed to investigate whether the impact of this drug on activity of the hypothalamic–pituitary–thyroid axis in women is impacted by the androgen status of patients. Methods: The study population included 48 levothyroxine-naïve reproductive-aged women with subclinical hypothyroidism and prediabetes receiving 3.0 g of metformin daily. Women with (n = 24) and without (n = 24) polycystic ovary syndrome were matched for age, insulin sensitivity, TSH, and reasons for thyroid hypofunction. Circulating levels of glucose, glycated hemoglobin, insulin, TSH, thyroid hormones, gonadotropins, androgens, estradiol, SHBG, prolactin, ACTH, and IGF-1 were measured before metformin treatment and six months later. Results: At entry, women with and without polycystic ovary syndrome differed in LH, LH/FSH ratio, androgens, and estradiol. The decrease in TSH, fasting glucose and glycated hemoglobin, and the improvement in insulin sensitivity were less pronounced in women with than in women without polycystic ovary syndrome. In each group, there were no differences in the impact on TSH and thyroid hormones between patients with subclinical hypothyroidism of autoimmune and non-autoimmune origin. The changes in TSH inversely correlated with total testosterone and free androgen index. Only in women with coexisting polycystic ovary syndrome, did metformin slightly reduce LH, LH/FSH ratio, testosterone, and free androgen index. Conclusions: The results suggest that concurrent polycystic ovary syndrome attenuates metformin action on TSH secretion, which can be explained by increased androgen production. Moreover, the drug seems to alleviate PCOS-associated changes in the activity of the reproductive axis. Full article

Sprouted grains are gaining attention as a natural and sustainable source of bioactive compounds with potential benefits in managing insulin resistance (IR), a hallmark of obesity-related metabolic disorders. This review aims to synthesize current findings on the biochemical changes induced during grain germination and their relevance to metabolic health. We examined recent in vitro, animal, and human studies focusing on how germination enhances the nutritional and functional properties of grains, particularly through the synthesis of compounds such as γ-aminobutyric acid, polyphenols, flavonoids, and antioxidants, while reducing anti-nutritional factors. These bioactive compounds have been shown to modulate metabolic and inflammatory pathways by inhibiting carbohydrate-digesting enzymes, suppressing pro-inflammatory cytokines, improving redox balance, and influencing gut microbiota composition. Collectively, these effects contribute to improved insulin sensitivity and glycemic control. The findings suggest that sprouted grains serve not only as functional food ingredients but also as accessible dietary tools for preventing or alleviating IR. Their role in delivering multiple bioactive molecules through a simple, environmentally friendly process highlights their promise in developing future nutrition-based strategies for metabolic disease prevention. Full article

Insulin resistance (IR), a core component in the development of type 2 diabetes mellitus (T2DM), is increasingly recognized for its role in cardiovascular and pulmonary complications. This review explores the relationship between IR, right ventricular dysfunction (RVD), and decreased lung volume in patients with T2DM. Emerging evidence suggests that IR contributes to early structural and functional alterations in the right ventricle, independent of overt cardiovascular disease. The mechanisms involved include oxidative stress, inflammation, dyslipidemia, and obesity—factors commonly found in metabolic syndrome and T2DM. These pathophysiological changes compromise right ventricular contractility, leading to reduced pulmonary perfusion and respiratory capacity. RVD has been associated with chronic lung disease, pulmonary hypertension, and obstructive sleep apnea, all of which are prevalent in the diabetic population. As RVD progresses, it can result in impaired gas exchange, interstitial pulmonary edema, and exercise intolerance—highlighting the importance of early recognition and management. Therapeutic strategies should aim to improve insulin sensitivity and cardiac function through lifestyle interventions, pharmacological agents such as SGLT2 inhibitors and GLP-1/GIP analogs, and routine cardiac monitoring. These approaches may help slow the progression of RVD and its respiratory consequences. Considering the global burden of diabetes and obesity, and the growing incidence of related complications, further research is warranted to clarify the mechanisms linking IR, RVD, and respiratory dysfunction. Understanding this triad will be crucial for developing targeted interventions that improve outcomes and quality of life in affected patients. Full article

Background: Chronic stress in childhood and adolescence leads to excessive cortisol secretion, adipokines production and obesity with all the negative mental and physical effects on the health of individuals and adulthood. Objectives: The aim of the present non-randomized controlled trial was to investigate the effect of a stress management protocol with diaphragmatic breathing (DB) and physiotherapy exercise on stress, body composition, cardiorespiratory and metabolic markers of children and adolescents with morbid obesity. Methods: The study included 31 children and adolescents (5–18 years old) with morbid obesity (22 in the intervention arm and 9 controls). All participants completed anxiety questionnaires and a self-perception scale. Forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), blood pressure (BP) and SpO₂ were measured. Fasting glucose, uric acid, triglycerides, HbA1c, (AST/SGOT), (ALT/SGPT), HDL, LDL, insulin, ACTH, cortisol, HOMA-IR, 17-OH, S-DHEA, SHBG were assessed, and anthropometric measurements were also performed. Results: In the intervention group, 4 months after the treatment, an improvement was noted in the BMI, BMI z-score, waist-to-height ratio, FEV1, SpO₂, pulse and systolic BP. HDL increased, ALT/SGPT and insulin resistance improved. Positive changes were observed in temporary and permanent stress and self-esteem of children in the intervention group, including anxiety, self-perception, physical appearance, etc. Conclusions: A combined exercise and DB protocol has a positive effect on stress, by improving body composition, reducing insulin resistance, and ameliorating physical and mental health and quality of life of pediatric patients with morbid obesity. Full article

Insulin resistance is a fundamental pathophysiological mechanism contributing to the development of type 2 diabetes and metabolic syndrome. Recently, attention has focused on mitochondria’s role in glucose and lipid metabolism. Mitochondrial dysfunction is strongly associated with impaired energy metabolism and elevated oxidative stress. We investigated the mitochondrial DNA (mtDNA) copy number in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in insulin-sensitive (IS) and insulin-resistant (IR) individuals. Twenty-seven paired adipose tissue biopsies were obtained during elective abdominal surgery. DNA and RNA were extracted, and mtDNA copy number was quantified using Real-Time PCR. We found that mtDNA content in VAT was approximately two-fold lower than in SAT. Furthermore, in IR individuals, mtDNA copy number was significantly reduced in both SAT and VAT compared to IS subjects. A strong positive correlation was observed between mtDNA content in VAT and body mass index (BMI), and a negative correlation was found with the QUICKI index. Additionally, mtDNA copy number in VAT positively correlated with the expression of several genes involved in insulin signalling, lipid metabolism, and other metabolic pathways. These findings underscore the central role of mitochondrial function in VAT in the context of metabolic disorders and suggest that targeting mitochondrial regulation in this tissue may represent a promising therapeutic approach. Full article

Cinnamic acid, an organic acid naturally occurring in plants of the Cinnamomum genus, has been highly valued for its medicinal properties in numerous ancient Chinese texts. This article reviews the chemical composition, pharmacological effects, and various applications of cinnamic acid and its derivatives reported in publications from 2016 to 2025, and anticipates their potential in medical and industrial fields. This review evaluates studies in major scientific databases, including Web of Science, PubMed, and ScienceDirect, to ensure a comprehensive analysis of the therapeutic potential of cinnamic acid. Through systematic integration of existing knowledge, it has been revealed that cinnamic acid has a wide range of pharmacological activities, including anti-tumor, antibacterial, anti-inflammatory, antidepressant and hypoglycemic effects. Additionally, it has been shown to be effective against a variety of pathogens such as Staphylococcus aureus, Pseudomonas aeruginosa, and foodborne Pseudomonas. Cinnamic acid acts by disrupting cell membranes, inhibiting ATPase activity, and preventing biofilm formation, thereby demonstrating its ability to act as a natural antimicrobial agent. Its anti-inflammatory properties are demonstrated by improving oxidative stress and reducing inflammatory cell infiltration. Furthermore, cinnamic acid enhances metabolic health by improving glucose uptake and insulin sensitivity, showing promising results in improving metabolic health in patients with diabetes and its complications. This systematic approach highlights the need for further investigation of the mechanisms and safety of cinnamic acid to substantiate its use as a basis for new drug development. Particularly in the context of increasing antibiotic resistance and the search for sustainable, effective medical treatments, the study of cinnamic acid is notably significant and innovative. Full article

Background/Objectives: Vitamin D supplementation has shown promise in managing type 2 diabetes mellitus (T2DM), while the simultaneous impact on glycemic control and inflammation in T2DM remains poorly understood. This study aimed to investigate the potential role of vitamin D supplementation in managing T2DM using fasting plasma glucose (FPG), insulin levels, HOMA-IR, HOMA-B, HbA1c, and Hs-CRP as the biomarkers. Methods: Original articles from Scopus, Pubmed, Cochrane Library, Epistemonikos, and ScienceDirect published between 2014 and 2024 were the sources. Inclusion criteria included studies conducted as clinical trials or randomized controlled trials involving adult patients diagnosed with T2DM undergoing treatment with vitamin D. The risk of bias was evaluated using the ROB-2 tool and meta-analysis was conducted to quantitatively synthesize the results across the studies using pooled effect sizes and confidence intervals. Results: Nine studies were included in the meta-analysis. Significant differences were found at 12-week follow-up in insulin level (MD(−3.59) [95% CI: −6.93, −0.25]), HOMA-B (MD(−50.35) [95% CI: −92.29, −8.41]), hs-CRP (−2.51 [95% CI: −3.45, −1.57]), and HbA1c level (MD(−0.30) [95% CI: −0.54, −0.06]) and at 24-week follow-up in HOMA-IR (MD(−0.38) [CI: −0.53, −0.24]). The quality of the included studies was generally moderate, with three showing a potential risk of bias. Conclusions: The observed trends in FPG, insulin levels, HOMA-IR, HOMA-B, HbA1c, and hs-CRP indicate that vitamin D may influence glycemic control, insulin sensitivity, and inflammation, but these effects are often modest and may diminish over time. Future studies should explore longer duration randomized trials with standardized dosing and baseline vitamin D status stratification. Full article

Benign prostatic hyperplasia (BPH) is a multifactorial condition that is highly prevalent and affects aging males. It frequently results in lower urinary tract symptoms (LUTS) and a reduced quality of life. While hormonal dysregulation and chronic inflammation have long been implicated in BPH pathogenesis, recent evidence highlights the role of physical activity in modulating prostate health. In this narrative review, evidence from quantitative studies examining the effect of exercise on BPH risk and symptom severity was first synthesized. Collectively, these studies suggest that regular physical activity is associated with a lower incidence and reduced progression of BPH. The potential mechanisms through which exercise may exert protective effects on the prostate were then explored. These include modulation of sympathetic nervous system activity, alterations in hormonal profiles (e.g., testosterone and insulin), suppression of chronic inflammation and oxidative stress, and the promotion of autophagy within prostatic tissue. Central to these mechanisms is the role of myokines—signaling molecules secreted by skeletal muscle during exercise. Key myokines, such as irisin, interleukin-6 (IL-6), brain-derived neurotrophic factor (BDNF), and myostatin, are reviewed in the context of prostate health. These molecules regulate inflammatory pathways, metabolic processes, and tissue remodeling. For instance, exercise-induced reductions in myostatin are linked to improved insulin sensitivity and decreased fat accumulation, while elevated irisin and BDNF levels may exert anti-inflammatory and metabolic benefits relevant to BPH pathophysiology. Although direct causal evidence linking myokines to BPH is still emerging, their biological plausibility and observed systemic effects suggest a promising avenue for non-pharmacological intervention. Future research should focus on identifying the specific myokines involved, elucidating their molecular mechanisms within the prostate, and evaluating their therapeutic potential in clinical trials. Full article