Search Results (151)

Background/Objectives: Non-caloric sweeteners are increasingly used as alternatives to sugar to reduce energy intake, yet their metabolic effects remain controversial. This study aimed to evaluate the effects of sucrose, saccharin, and steviol glycosides on glucose regulation and cardiometabolic risk markers in healthy adults. Methods: In a randomized, double-blind, crossover trial, 39 healthy, normal-weight adults consumed beverages containing sucrose (66 g/day), saccharin (220 mg/day), or steviol glycosides (220 mg/day) for 14 days, with washout periods between interventions. Metabolic outcomes were assessed at baseline and after each intervention under fasting conditions and during a 2 h postprandial test. Primary outcomes were glucose and insulin responses; secondary outcomes included gut hormones, lipids, inflammatory markers, and subjective appetite. Results: Compared with baseline, fasting glucose increased after sucrose and saccharin, and fasting insulin increased after stevia (p < 0.01). All interventions increased postprandial insulin responses and reduced indices of insulin sensitivity (p < 0.05). Fasting PYY and GLP-2 increased following all treatments (p < 0.001), without differences between sweeteners. Triglycerides were higher after sucrose than saccharin (p < 0.05), while no differences were seen for cholesterol, apolipoproteins, or CRP. Appetite ratings were unchanged, with a trend (p = 0.053) towards a reduced desire to eat after stevia in the late postprandial phase. Conclusions: Short-term intake of sucrose and non-caloric sweeteners resulted in broadly similar metabolic responses, with no significant differences in glucose regulation. However, triglyceride concentrations were higher following sucrose than saccharin, whereas no consistent differences were observed across the remaining outcomes. Observed deviations from baseline should be interpreted with caution. Further long-term studies in diverse populations are warranted. Full article

Dietary fiber is an under-consumed nutritional substrate that supports gut microbial metabolism, intestinal barrier integrity, enteroendocrine signaling, and cardiometabolic regulation. Among dietary fibers, psyllium and glucomannan are clinically accessible viscous, gel-forming soluble fibers with distinct but complementary physicochemical profiles. This narrative review examines how these fibers act through luminal viscosity, nutrient diffusion, bile acid and cholesterol handling, short-chain fatty acid production, epithelial barrier support, enteroendocrine L-cell signaling, and low-grade metabolic inflammation. Psyllium has the strongest clinical support for stool normalization, glycemic modulation, and LDL cholesterol reduction, whereas glucomannan provides marked viscosity and water-holding capacity that may support satiety, lipid modulation, and weight-management strategies when appropriately hydrated and tolerated. We also discuss the emerging nutritional context of glucagon-like peptide-1 receptor agonist therapy, in which appetite suppression, reduced meal volume, delayed gastrointestinal transit, and constipation may reduce dietary fiber intake and fermentable substrate delivery to the colon. The pain- and mood-related implications are framed as hypothesis-generating extensions, because direct clinical evidence that psyllium or glucomannan improves these outcomes remains limited. A psyllium-centered, selectively glucomannan-supported strategy may help close the fiber gap and support bowel function, microbial metabolite signaling, and cardiometabolic stability during modern metabolic and weight-loss therapies. Full article

Background: C-reactive protein (CRP) is a well-established marker of systemic inflammation, while Growth Differentiation Factor-15 (GDF-15) has emerged as a potential biomarker of cellular stress. Their relative perioperative dynamics remain incompletely defined. This prospective observational study aimed to explicitly characterize and compare the longitudinal dynamics of CRP and GDF-15 in patients undergoing elective knee arthroplasty. Characterizing these biomarkers in a controlled acute surgical model provides clinical relevance by mapping systemic acute-phase inflammation against cellular stress pathways, which may offer a baseline reference for evaluating chronic tissue-wasting states. Methods: This prospective observational study included 47 patients undergoing elective knee arthroplasty. After excluding nine patients with elevated baseline CRP (>10 mg/L), serial measurements of CRP and GDF-15 were analysed daily in 38 patients from pre-operation to postoperative Days 1–3. Results: CRP rose sharply after surgery, peaking on Day 3 (median: 206.0 mg/L vs. baseline: 3.0 mg/L), representing a maximal increase exceeding 6100%. GDF-15 levels also increased progressively, peaking on Day 3 (median: 1682.5 pg/mL vs. baseline: 968.8 pg/mL), which represented a statistically significant but more modest rise of 33%. CRP and GDF-15 were significantly correlated on postoperative day 1 (rs = 0.53, p = 0.001) but not days 2 and 3. Baseline GDF-15, but not CRP, was significantly associated with oral hypoglycaemic agent use and vitamin B12 supplementation. Compared to values reported in recent randomized trials of ghrelin, anti-GDF-15, and anti-IL-6 therapies, GDF-15 levels in this surgical cohort remained lower, while CRP approached levels observed in such studies. Conclusions: CRP and GDF-15 rise in parallel following surgical injury; however, GDF-15 shows a considerably lower sensitivity to the inflammatory response. These findings suggest a complementary role of GDF-15 alongside CRP in profiling the perioperative stress response. While its relatively modest acute elevation limits its utility as a primary marker of acute inflammation, this surgical stress model serves as a reference that may help contextualize biomarker profiles in chronic inflammatory or wasting conditions, such as cancer cachexia, rather than serving as a direct tool for cachexia management. Full article

Obesity is a major global health problem and is closely associated with a broad range of metabolic disorders, including metabolic syndrome (MetS), dyslipidemia, hypertension, atherosclerosis, type 2 diabetes mellitus, and cardiovascular disease. The gut microbiota plays a central role in maintaining intestinal epithelial integrity, regulating glucose and lipid metabolism, and modulating immune function. Through the gut–brain axis, it also contributes to appetite regulation and energy homeostasis by influencing the release of anorexigenic hormones. Dysbiosis, including alterations in the relative abundance of major bacterial phyla such as Firmicutes and Bacteroidetes, has been associated with increased intestinal permeability, metabolic endotoxemia, and chronic low-grade inflammation, all of which may contribute to the development of obesity and insulin resistance. Diets rich in plant-derived fiber can beneficially shape gut microbiota composition. Bacterial fermentation of dietary fiber produces short-chain fatty acids (SCFAs), including butyrate, acetate, and propionate, which contribute to intestinal barrier integrity, inflammatory regulation, immune regulation, and metabolic homeostasis. Overall, the interaction between gut microbiota, diet, and host metabolic pathways represents a promising field for therapeutic and nutritional interventions aimed at preventing and managing MetS and metabolic diseases. Full article

Background: Nutritional deterioration and systemic inflammation are prevalent in cancer patients undergoing chemotherapy and may independently impair health-related quality of life (QoL). Yet their simultaneous, domain-specific contributions to QoL remain poorly characterized, particularly in Middle Eastern populations. Methods: This cross-sectional study included adult cancer patients receiving chemotherapy. Medical records were used to collect clinical and laboratory data. Structured interviews were conducted to assess nutritional status using the Malnutrition Universal Screening Tool (MUST) and quality of life using the EORTC QLQ-C30 questionnaire. The NLR was calculated as an indicator of systemic inflammation. Multiple linear regression models, adjusted for age, sex, cancer site, stage, and treatment cycle, were used to examine independent associations with QoL domains. Results: Nearly 60% of patients were at a medium-to-high malnutrition risk and 27.1% exhibited high systemic inflammation (NLR > 3). The NLR was significantly associated with greater dyspnea (B = 28.4, p = 0.001), and the MUST was significantly associated with greater appetite loss (B = 17.0, p = 0.001). Additional significant associations included the NLR with poorer physical functioning (p = 0.009) and role functioning (p = 0.012), and the MUST with nausea and vomiting (p = 0.039). In the multivariate analysis, the NLR showed a statistically significant overall effect on the QoL profile (p = 0.007), while the MUST did not (p = 0.281), consistent with its more domain-specific pattern. Conclusions: This cross-sectional study suggests that systemic inflammation and nutritional risk are associated with domain-specific quality of life among cancer patients receiving chemotherapy. The NLR and MUST may represent accessible, complementary indicators of patient vulnerability and supportive care needs. Prospective multi-center studies are warranted to validate these associations and determine their clinical utility in supportive oncology practice. Full article

Obesity is a growing public health concern linked to poor dietary habits, physical inactivity, and metabolic disturbances, which can be evaluated using complementary laboratory tests. Among pharmacological interventions, semaglutide, a GLP-1 receptor agonist, has shown promise by acting on the central nervous system to reduce appetite and stimulate insulin secretion, thereby improving the lipid profile and reducing inflammation biomarkers. This review focused on changes in lipid parameters and C-reactive protein (CRP) levels in overweight or obese individuals treated with semaglutide, based on phase 3 studies from the STEP program (“Semaglutide Treatment Effect in People with Obesity”). The STEP clinical trial program was conducted across 36 countries, reflecting a broad and diverse geographic representation. Key findings include significant reductions between placebo vs. semaglutide in body weight (−1.3 vs. −13.0 Kg), body mass index (−0.69 vs. −4.72 kg/m²), and waist circumference (−2.79 × −11.81 cm). Additionally, there were notable decreases in triglycerides (−0.67 vs. −20.89%), VLDL-C (−0.99 vs. 20.82%), and CRP levels (−15.45 vs. −55.55%). These changes reflect improvements in both inflammatory and metabolic markers. The observed benefits suggest that semaglutide may contribute to reducing comorbidities associated with metabolic syndrome and to the prevention of cardiovascular disease. Current evidence also supports its potential role in individualized treatment strategies based on patients’ clinical and biochemical profiles. However, despite these promising findings, further long-term studies are required to confirm the efficacy and safety of semaglutide across diverse populations. Full article

Janus kinase (JAK) inhibitors have become an important therapeutic option for a wide range of immune-mediated inflammatory diseases. By targeting intracellular cytokine signaling through inhibition of the JAK–STAT pathway, these agents provide effective suppression of multiple inflammatory cascades. Alongside their growing clinical use, changes in body weight—particularly weight gain—have recently been reported in clinical practice. Although this phenomenon has not consistently emerged as a prominent adverse event in randomized clinical trials, observational studies and real-world data suggest that weight gain may occur in some of the treated patients. The mechanisms underlying these changes remain barely understood and are likely multifactorial. Effective suppression of systemic inflammation may reverse inflammation-driven catabolism and restore metabolic balance, contributing to increases in body weight and lean body mass. In addition, experimental evidence indicates that JAK–STAT signaling participates in adipocyte differentiation, lipid metabolism, and energy regulation. Pharmacologic inhibition of this pathway may therefore influence adipose tissue biology, thermogenic activity, and appetite regulation through leptin-dependent signaling pathways. This review summarizes current evidence regarding weight and body composition changes associated with JAK inhibitor therapy, integrating findings from experimental studies, clinical trials, and real-world observations. Potential biological mechanisms are discussed alongside patient-related and disease-related factors that may modify the risk of weight gain. A better understanding of these immune–metabolic interactions may help guide clinical monitoring and future research on the metabolic consequences of JAK inhibition. Full article

Metabolic diseases, including obesity, type 2 diabetes, and their related complications, have emerged as major global public health challenges. Increasing evidence indicates that gut microbiota dysbiosis contributes to disrupted metabolic homeostasis, chronic low-grade inflammation, and progression of metabolic disorders. Among candidate microbiome-based interventions, Lactiplantibacillus plantarum (L. plantarum) and Akkermansia muciniphila (A. muciniphila) have attracted particular attention because they regulate host metabolism through partially distinct yet potentially complementary mechanisms. L. plantarum has been associated with modulation of appetite-related hormones, adipose tissue remodeling, reinforcement of intestinal barrier function, and attenuation of inflammatory signaling. A. muciniphila has been linked to strengthening of the mucus barrier, production of beneficial metabolites, and improvement in immune and metabolic homeostasis. However, current evidence remains fragmented across strain-specific studies, heterogeneous formulations, and predominantly single-strain experimental designs, and direct comparative evidence for combined administration is still limited. This review synthesizes current epidemiological, mechanistic, preclinical, and clinical evidence on L. plantarum and A. muciniphila, with emphasis on their physiological traits, gut ecological adaptability, pathway-based metabolic effects, and translational challenges in obesity, type 2 diabetes, and related complications. We further highlight the ecological rationale for their functional complementarity and discuss priorities for future combination studies and precision implementation. Overall, the available literature supports functional complementarity and possible additive metabolic benefits, but synergistic effects in humans remain unconfirmed. A clearer understanding of strain identity, active therapeutic entities, delivery strategies, and host context will be essential for advancing this dual-target microbial strategy toward clinically meaningful applications. Full article

Background: Understanding how endogenous hormonal fluctuations and exogenous hormonal modulation influence exercise-related outcomes in women is essential for developing individualized and evidence-informed training and nutritional strategies. This narrative review summarizes the endocrine physiology of the eumenorrheic menstrual cycle and hormonal contraceptive (HC) use and critically examines their implications for athletic performance, neuromuscular function, injury risk, and metabolic regulation in physically active women. Methods: A non-systematic literature search was conducted in PubMed, Scopus, and Web of Science for articles published up to January 2026. Search terms combined menstrual cycle-related, hormonal contraceptive, performance, and metabolic/nutritional keywords, and relevant studies were selected based on their relevance to the scope of this narrative review. Results: Estradiol and progesterone fluctuations may modulate substrate utilization, connective tissue properties, central fatigue regulation, and symptom expression; however, evidence indicates that performance-related effects across menstrual phases are generally small and inconsistent, reflecting both the modest magnitude of physiological effects and the methodological heterogeneity in menstrual cycle phase classification and verification across studies. Similarly, although HC use suppresses endogenous hormonal variability, current findings do not support consistent benefits for performance, injury prevention, or metabolic outcomes, and responses remain heterogeneous. From a nutritional perspective, the endocrine context may contribute to modest changes in energy expenditure, insulin sensitivity, appetite regulation, inflammation, and recovery-related processes. Importantly, symptom burden—including pain, fatigue, sleep disturbances, gastrointestinal discomfort, and fluid retention—emerges as a practical driver of day-to-day training tolerance. Conclusions: We propose an integrative framework in which sex hormones define a physiological context rather than deterministic performance regulators, while nutrition acts as a key modifiable factor influencing metabolic responses, symptom severity, and performance consistency. Full article

Diet is a key modulator of the gut microbiota, thereby influencing host physiology. Microbial colonization begins early in life, influenced by maternal sources, mode of birth, diet, and environmental exposures, and stabilizes into an adult-like microbiome during early childhood. This maturation yields a microbial ecosystem dominated by Firmicutes and Bacteroidetes that contributes to host physiological homeostasis. Gut microorganisms function as an integrated metabolic system that transforms dietary substrates into bioactive metabolites, including short-chain fatty acids (SCFAs), amino acid-derived compounds, and microbial lipids. These metabolites regulate glucose and lipid metabolism, intestinal barrier integrity, and immune modulation. Although many metabolic functions are conserved, their activity is shaped by diet, microbial cross-feeding, and local intestinal conditions, enabling functional specialization within the gut. Disruption of this system, known as dysbiosis, is associated with alterations in microbial diversity and metabolic output that have been linked to metabolic diseases, including obesity and related disorders. Evidence from experimental models and observational studies suggests that these associations may involve interconnected inflammatory and metabolic mechanisms, such as impaired intestinal barrier function, low-grade inflammation, and altered dietary energy harvest; however, causal relationships in humans remain incompletely understood. Beyond peripheral effects, the gut microbiome influences host metabolism via the gut–brain axis, a bidirectional network that integrates neural, endocrine, immune, and metabolic signaling. Microbiota-derived metabolites and gut hormone modulation contribute to appetite regulation, energy balance, and glucose homeostasis, while central neuroendocrine signaling can reciprocally shape the intestinal microbial niche. Collectively, these findings highlight the gut microbiome as a central regulator of host metabolism, whose disruption may contribute to the development of metabolic disease. Full article

The substitution of fish meal with soybean meal (SBM) in aquafeeds aligns with sustainable development but often leads to depressed feed intake and growth in fish. This study aimed to investigate the mitigating effect of earthworm powder (EP) on these negative impacts in rice field eels (Monopterus albus), focusing on appetite regulation, intestinal health, and gut microbiota. Three isonitrogenous (~41% crude protein) and isolipidic (~6.4% crude lipid) diets (control [CON], high-SBM [SBM], and SBM + 2.5% EP [EP]) were tested in a 56-day trial. Juveniles (initial weight 18.00 ± 0.01 g) were stocked at 40 fish per net (0.5 m × 0.5 m× 0.5 m) and fed to visual satiety once daily. The results indicated that EP improved growth performance through a dual mechanism. Firstly, it was associated with significantly increased feed intake, correlated with the upregulated expression of orexigenic genes (agrp, npy) in the brain, and associated with reduced levels of anorexigenic hormones (Cholecystokinin, Leptin). Secondly, it correlated with enhanced intestinal health, evidenced by improved morphology (villus height, goblet cells), improved digestive enzyme activity, enhanced antioxidant capacity (increased Catalase and Superoxide Dismutase activities), repaired intestinal barrier function (upregulated zo-1, cla-12), and alleviated intestinal inflammation (downregulated tnf-α, il-1β). Furthermore, EP supplementation was associated with a shift in gut microbiota, including the suppression of the potential pathogen g_Clostridium_T and promotion of the beneficial bacterium g_Lactococcus_A, alongside increased concentrations of major short-chain fatty acids (acetate, propionate, and butyrate). These correlative observations suggest that EP may help mitigate the growth-inhibiting effects of SBM in Monopterus albus, offering a potential functional strategy for high-SBM aquafeeds. Full article

Background: Obesity is characterized by chronic low-grade systemic inflammation that contributes to metabolic dysfunction. Diet is a modifiable factor that can help reduce this inflammation. Nuts such as almonds are rich in unsaturated fats, and antioxidant and anti-inflammatory micronutrients, which may work synergistically to attenuate obesity-related inflammation. Hence, the objective of this study was to investigate whether daily almond consumption improves systemic inflammatory and immune markers in adults with obesity. Methods: In this randomized controlled parallel-arm trial (ClinicalTrials.gov ID NCT05530499), 69 adults (age 30–45 years) with obesity (BMI 30–45 kg/m²) were assigned to consume either 57 g/day of almonds (n = 38) or an isocaloric snack (cookie; n = 31) for six weeks. Fasting serum inflammatory cytokines, innate immune cell counts, body weight, serum glucose, insulin, lipid profile, and alpha-tocopherol were measured at baseline and week six. Dietary intake, compliance, palatability, acceptance, and appetite ratings were also assessed. Primary outcomes were analyzed using linear mixed models and baseline-adjusted linear models. Results: Subjective compliance was high in both groups, with greater acceptance of almonds (p < 0.05); however, serum alpha-tocopherol did not change. Almond consumption significantly decreased serum IL-6, TNF-α, and IFN-γ over 6 weeks compared with the cookie group (p < 0.05). No significant group differences were observed for innate immune cell counts, body weight, appetite ratings, blood pressure, or serum fasting glucose, insulin, total cholesterol (C), LDL-C, and triglycerides over six weeks. The almond group also increased intakes of monounsaturated fat, fiber, alpha-tocopherol, magnesium, zinc, and manganese, and improved diet quality indices relative to the cookie group (p < 0.05). Conclusions: Daily almond consumption for six weeks improved inflammatory cytokine profiles in adults with obesity, without changes in body weight under free-living conditions. These findings support recommending almonds as part of healthy dietary patterns to help attenuate obesity-related inflammation. Full article

Incretin hormones, such as glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), are essential regulators of glucose homeostasis, energy balance, and metabolic communication between organs. While therapies based on incretins are well established for type 2 diabetes (T2DM), their physiological significance and therapeutic potential in type 1 diabetes (T1DM) are less understood. In T1DM, the autoimmune destruction of pancreatic β-cells greatly reduces but does not abolish insulin production. However, various extrapancreatic actions of incretins continue, including effects on gastric emptying, glucagon secretion, appetite, inflammation, and cardiovascular function. The increasing prevalence of overweight, obesity, and insulin resistance among individuals with T1DM has heightened interest in exploring incretin-based treatments as adjuncts to insulin therapy. Data from randomized controlled trials, retrospective cohorts, and mechanistic studies were analyzed. This narrative review synthesizes available experimental, clinical trial, and real-world evidence on the physiology of incretins, their altered actions in T1DM compared with T2DM, and the effects of GLP-1 receptor agonists (GLP-1RAs) and tirzepatide, a dual GIP/GLP-1 agonist, on glycemic control, body weight, and cardiovascular outcomes in patients with T1DM. The use of GLP-1RAs in T1DM showed a weight reduction between 3.6 kg and 8.8 kg and improved glycated hemoglobin (HbA_1c) by 0.2–0.8%, while treatment with tirzepatide for 6 months resulted in a body weight change of −10.3 to −10.6 kg. Growing evidence suggests a significant role of incretins in certain patients with T1DM, although large-scale, adequately powered randomized controlled trials are necessary to confirm their long-term efficacy and safety. Full article

Background/Objectives: Obesity is characterized by dysregulated hypothalamic energy homeostasis and reduced central responsiveness to the anorexigenic hormones leptin and insulin. β-Hydroxybutyrate (β-HB), a major ketone body, has recently garnered attention as a signaling metabolite. However, its effects on hypothalamic leptin and insulin responsiveness remain unclear. This study aimed to investigate the effects of β-HB on hypothalamic hormone responsiveness and the associated molecular mechanisms, primarily using a high-fat diet (HFD)-induced obese mouse model. Methods: Male mice were fed an HFD to induce obesity and treated with β-HB via oral or intracerebroventricular (ICV) administration. Feeding behavior following leptin and insulin administration was evaluated, and activation of hypothalamic leptin-induced STAT3 signaling and insulin-induced Akt signaling was analyzed. In addition, mRNA expression of inflammation-related and appetite-regulating genes was assessed by quantitative PCR. Normal mice also received chronic ICV administration of β-HB from the onset of HFD feeding, and changes in body weight and cumulative food intake were measured. Results: Both oral and ICV administration of β-HB significantly enhanced the anorexigenic responses to leptin and insulin in HFD-induced obese mice. At the molecular level, leptin-induced STAT3 phosphorylation and insulin-induced Akt phosphorylation were enhanced in the hypothalamus. Gene expression analysis revealed reduced SOCS3 and TNFα expression and increased POMC expression. Furthermore, chronic ICV administration of β-HB from the onset of HFD feeding significantly suppressed body weight gain and the increase in cumulative food intake. Conclusions: This study demonstrates that β-HB improves hypothalamic leptin and insulin responsiveness in obese mice and modulates the associated molecular environment. These findings suggest that β-HB acts as a metabolically responsive signaling molecule regulating hypothalamic function, providing a basis for novel metabolic intervention strategies against obesity. Full article

Metabolic diseases such as type 2 diabetes and obesity are increasingly recognized as disorders of dysregulated cellular communication rather than solely enzymatic or transcriptional dysfunction. While conventional therapies primarily target metabolic enzymes and nuclear receptors, growing evidence highlights ion channels and G protein-coupled receptors (GPCRs) at the cell membrane as critical upstream regulators of glucose homeostasis, energy expenditure, and inflammation. Cinnamon (Cinnamomum spp.), a widely consumed nutraceutical, has demonstrated consistent antidiabetic and antiobesity effects; however, its actions at the membrane signaling interface remain underappreciated. This review synthesizes emerging evidence that cinnamon-derived phytonutrients, particularly cinnamaldehyde, eugenol, and polyphenolic compounds, modulate key ion channels and GPCR pathways involved in metabolic regulation. We discuss how cinnamon influences calcium signaling, transient receptor potential (TRP) channels, and metabolite- and hormone-sensing GPCRs, thereby affecting insulin secretion, incretin release, appetite control, thermogenesis, and inflammatory tone. A central highlight of this review is the crosstalk between ion channels and GPCRs in metabolic tissues, illustrating a systems-level mechanism through which cinnamon exerts pleiotropic metabolic benefits. Translational implications are explored, including the potential of cinnamon to complement existing antidiabetic therapies and its relevance within precision nutrition frameworks. By focusing on the cell membrane as an integrative signaling hub, this review reframes cinnamon as a membrane-active nutraceutical capable of restoring metabolic balance through coordinated modulation of ion channel GPCR networks. Full article