Search Results (1,268)

Multipotent mesenchymal stromal stem cells have captivated the scientific community in recent years due to their ability to differentiate into multiple adult cell types. Central to this potential are many members of the nuclear hormone receptor superfamily, comprising 48 ligand-modulated transcription factors involved in key biological processes such as metabolism, physiology, embryonic development, and reproduction. These transcription factors influence cellular fate by regulating gene expression networks critical for MSC specification, commitment, and differentiation. This review explores the role of nuclear receptors in MSC development, focusing on interactions with chromatin structure, co-regulatory complexes, and responsiveness to extracellular stimuli such as hormones, metabolic cues, and endocrine-disrupting chemicals. We conclude with a discussion of the dangers posed by exogenous and aberrant signaling through nuclear receptors. Full article

Background/Objectives: This review integrates evolutionary, metabolic, genetic, and nutritional perspectives to explain how sterol-derived vitamin D pathways shape human physiology and inter-individual variability in vitamin D status. Methods: The literature on sterol and vitamin D metabolism across animals, plants, fungi, and algae was synthesized with data from metabolomics databases, genome-wide association studies, RNA-seq resources (including GTEx), structural biology, and functional genomics. Results: Vitamin D₂ and vitamin D₃ likely emerged early in evolution as non-enzymatic photochemical sterol derivatives and were later co-opted into a tightly regulated endocrine system in vertebrates. In humans, cytochrome P450 enzymes coordinate vitamin D activation and degradation and intersect with oxysterol production, thereby linking vitamin D signaling to cholesterol and bile acid metabolism. Tissue-specific gene expression and regulatory genetic variants, particularly in the genes DHCR7, CYP2R1, CYP27B1, and CYP27A1, contribute to population-level differences in vitamin D status and metabolic outcomes. Structural analyses reveal selective, high-affinity binding of 1,25-dihydroxyvitamin D₃ to VDR, contrasted with broader, lower-affinity ligand recognition by LXRs. Dietary patterns modulate nuclear receptor signaling through distinct yet convergent ligand sources, including cholesterol-derived oxysterols, oxidized phytosterols, and vitamin D₂ versus vitamin D₃. Conclusions: Sterol and vitamin D metabolism constitute an evolutionarily conserved, adaptable network shaped by UV exposure, enzymatic control, genetic variation, and diet. This framework explains inter-individual variability in vitamin D biology and illustrates how evolutionary and dietary modulation of sterol-derived ligands confers functional flexibility to nuclear receptor signaling in human health. Full article

Alzheimer’s disease (AD) is a chronic neurodegenerative disorder characterized by progressive loss of cognitive function. Its main pathological features include accumulation of Amyloid-beta (Aβ) plaques, excessive phosphorylation of microtubule-associated protein tau (tau protein), and neuroinflammation. In recent years, studies have confirmed intestinal flora is closely connected to AD. Gut–brain axis has an important part in AD. Intestinal flora can achieve signal communication between gut and brain through metabolic, immune, neural, and endocrine pathways, thereby slowing down AD. It has been discovered that exercise is not only beneficial to physical health but also has a positive impact on the brain function. In recent years, more and more studies have found exercise can alleviate AD through the following four major pathways: regulating the diversity of intestinal flora, strengthening the blood–brain barrier (BBB), regulating immune homeostasis, and upregulating the brain-derived neurotrophic factor (BDNF). In this review, we have summarized intestinal flora in AD and systematically expounded potential regulatory pathways of exercise in modulating intestinal flora for AD. This provides a more theoretical basis for subsequent research targeting “gut–brain axis” to regulate AD. At the same time, this review also summarizes differences in different exercise types on improving intestinal flora for alleviating AD, providing new ideas and strategies for AD. Full article

Introduction: Multiple sclerosis (MS) is a chronic autoimmune inflammatory disorder of the central nervous system (CNS) that leads to demyelination of CNS neurons and is influenced by genetic, environmental, and lifestyle factors, including diet and obesity. Methods: This review aims to analyze at the molecular level the relationship between obesity, as a chronic inflammatory condition, and the pathophysiology of MS, as a chronic autoimmune inflammatory disease, in order to understand the complex links between obesity and MS through a search of the PubMed and Google Scholar databases. Discussion: Chronic inflammation and OS are interconnected processes, causing a toxic state, which contributes to the development of CNS neuroinflammation and neuronal damage, resulting in neuronal demyelination and the onset of MS. Adipose tissue is a complex endocrine organ; in addition to being a lipid storage organ, it secretes cytokines and adipokines, which are involved in the regulation of hormones, metabolism, inflammation, and whole-body homeostasis. Obesity triggers chronic low-grade inflammation, disruption of the blood–brain barrier (BBB) and brain metabolism, infiltration of the CNS by immune cells, production of ROS, and generation of oxidative stress (OS). Anti-inflammatory and pro-inflammatory adipokines are also implicated in MS and obesity. Conclusions: Obesity affects MS through common underlying mechanisms and seems to be a modifiable risk factor. Antioxidant and anti-inflammatory compounds with multi-functional characteristics could be additional tools to slow the progression of MS and its promotion through obesity while also offering potential treatment options for both conditions via their multi-targeting characteristics. Full article

Background/Objectives: Replacing fish oil with vegetable oil is an important measure for aquaculture to relieve the pressure of fish oil, but it is also easy to cause the growth decline and metabolic disorder of farmed animals, mainly due to the change in dietary fatty acids. This study investigated the regulatory effects of dietary fatty acid composition on glucose metabolism in large yellow croaker (Larimichthys crocea) with an initial weight of 30.51 ± 0.16 g. Methods: Three isonitrogenous (~43% crude protein) and isolipid (~11% crude lipid) diets were formulated as follows: control (CON, DHA/EPA-rich oil as primary lipid), moderate palmitic acid (MPA, 50% of DHA+EPA-rich oil was replaced by glyceryl palmitate), and high palmitic acid (HPA, 100% of DHA+EPA-rich oil was replaced by glyceryl palmitate). Results: After 10 weeks of feeding, the HPA significantly reduced the liver/muscle glycogen contents, increased the liver lipid content, decreased the serum leptin/insulin level, and increased the adiponectin level. The levels of DHA and EPA in liver were decreased significantly. Transcriptionally, HPA upregulated hepatic glucokinase (gk, glycolysis) but down-regulated glycogen synthase (gys) and insulin/irs2 (insulin pathway) while inhibiting muscle ampk and leptin receptor (lepr). Conclusions: This study showed that high dietary PA/(DHA + EPA) impacted glycolipid homeostasis through endocrine and transcriptional regulation, leading to increased crude lipid and decreased glycogen levels, which provides a theoretical basis for scientific aquatic feed fatty acid formulation. Full article

Calcium ions (Ca²⁺) serve as universal second messengers regulating endocrine, neuronal, and metabolic processes. In children and adolescents, tight calcium signaling control is crucial for growth, hormone homeostasis, neuromuscular function, and neurodevelopment. Disruptions in Ca²⁺-dependent pathways—whether genetic, metabolic, or acquired—underlie a spectrum of pediatric endocrine diseases often presenting with neurological manifestations This review summarizes calcium’s roles in hormone secretion, parathyroid and vitamin D metabolism, and neuronal excitability, and discusses monogenic and metabolic disorders affecting calcium sensing and signaling, including CASR, GNA11, AP2S1, STIM1, and ORAI1 mutations. Diagnostic challenges, therapeutic strategies, and future directions for precision medicine in pediatric neuroendocrinology are highlighted, emphasizing early recognition and improved clinical outcomes. Full article

Brown adipose tissue (BAT) and beige adipocytes play a crucial role in adaptive thermogenesis, primarily via uncoupling protein 1 (UCP1)-driven heat production. Once considered physiologically irrelevant in adults, BAT is now recognized as an active tissue that contributes to energy expenditure and metabolic homeostasis and represents a potential therapeutic target for obesity and metabolic disorders. This review provides an integrated overview of the molecular regulation of thermogenic adipocytes, emphasizing both canonical UCP1-dependent as well as non-canonical UCP1-independent mechanisms of heat generation. Key transcriptional and epigenetic regulators are discussed in the context of mitochondrial biogenesis, substrate utilization, and thermogenic gene programs. Major upstream signaling routes are further summarized, encompassing classical β-adrenergic pathways, as well as alternative regulatory nodes including AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin (mTOR) together with diverse nutrient- and hormone-responsive cues that converge to activate brown and beige adipocytes. Finally, the cross-talk among neuronal, endocrine, immune, and gut microbiota-derived signals is highlighted as a key determinant of thermogenic adipocyte function. Together, these multilayered regulatory inputs provide a comprehensive framework for understanding how thermogenic adipose tissue integrates environmental, metabolic, and microbial cues to regulate systemic energy balance—knowledge that is essential for developing targeted therapies to combat obesity and metabolic diseases. Full article

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by abdominal pain, altered motility, and visceral hypersensitivity. Emerging evidence implicates G protein-coupled receptors (GPCRs) as key integrators of microbial, immune, endocrine, and neural signals in IBS pathophysiology. This review summarizes recent advances in understanding how GPCRs mediate gut immune regulation, microbiota–host crosstalk, metabolic signaling, and pain processing in IBS. Recent studies show that microbial metabolites (e.g., short-chain fatty acids, biogenic amines, and lipid mediators) signal through GPCRs on immune cells, epithelia, and neurons to influence intestinal homeostasis. On immune cells and neurons, GPCRs also mediate signals from external substances (such as fats, sugars, histamine, etc.) to regulate immune and neural functions. And there are challenges and future directions in targeting GPCRs for IBS, including patient heterogeneity and the complexity of host–microbiome interactions. This review provides a mechanistic framework for GPCR-based therapies in IBS. Full article

The objective of this study was to evaluate the protective effect of curcumin (Cur) on reproductive toxicity induced by fumonisin B₁ (FB₁) in laying ducks during the peak egg-laying period. A total of seventy-two 50-week-old Cherry Valley ducks were randomly assigned to four groups: control, FB₁ (30 mg/kg), Cur (200 mg/kg), and Cur + FB₁ (200 mg/kg + 30 mg/kg). The experiment lasted for 35 days. Our results showed that cur supplementation effectively restored the reductions in final body weight (p = 0.005) and oviduct length (p = 0.020) induced by FB₁ exposure. Residual FB₁ concentrations in serum, liver, and ovaries were markedly increased in the FB₁-treated group, while Cur significantly decreased the FB₁ residual in duck liver (p < 0.05). Meanwhile, Cur supplementation markedly counteracted the FB₁-induced reductions in serum total protein, albumin, triglycerides, and high-density lipoprotein induced by FB₁ exposure. Cur supplementation effectively regulated FB₁-induced oxidative stress, inflammation, and endocrine disruption. Specifically, Cur lowered FB₁-induced malondialdehyde levels (p < 0.010), attenuated interleukin-1β increase (p = 0.083), and reversed the reduction in immunoglobulin G levels. FB increased the levels of hormones associated with duck reproduction, including estradiol, follicle-stimulating hormone, and luteinizing hormone; in contrast, curcumin supplementation decreased the levels of these hormones (p < 0.010). Histopathological analysis revealed that Cur significantly alleviated the inflammation and necrosis in the liver, kidneys, ovaries, and oviducts induced by FB₁. In conclusion, dietary Cur supplementation effectively alleviated FB₁-induced reproductive toxicity in laying ducks by enhancing antioxidant capacity, improving lipid metabolism, and restoring hormonal homeostasis. Full article

Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by chronic low-grade inflammation. The NLRP3 inflammasome has been implicated in various inflammatory conditions, but its role in PCOS remains unclear. This study aimed to investigate whether the NLRP3 inflammasome and its associated components, IL-1β, CASP-1, and PYCARD, are involved in the pathogenesis of PCOS. Gene and protein expression levels of NLRP3, IL-1β, CASP-1, and PYCARD were assessed in adipose tissue samples (visceral and subcutaneous) from women with and without PCOS using qPCR and Western blotting. Contrary to our initial hypothesis, CASP-1 gene expression was significantly higher in non-PCOS participants across all adipose depots examined. Similarly, NLRP3 protein levels were significantly upregulated in visceral adipose tissue (VAT) and in combined adipose samples from the non-PCOS group. No significant group differences were observed in the gene expression of NLRP3, IL-1β, or PYCARD. These findings suggest a more complex role for the NLRP3 inflammasome in PCOS than previously assumed. The elevated CASP-1 and NLRP3 levels in non-PCOS participants may reflect compensatory regulation, subclinical inflammation in controls, or technical variability. Further research is needed to explore alternative inflammasome pathways and the influence of metabolic factors, such as insulin, on inflammasome regulation in PCOS. Full article

Testosterone is a key regulator of male and female physiology, influencing reproductive function, muscle and bone anabolism, metabolic homeostasis, and psychological well-being. Growing evidence indicates a secular, age-independent decline in testosterone levels across populations, a trend associated with reduced fertility, metabolic and cardiovascular dysfunction, mood disturbances, and impaired quality of life. While aging and genetic factors play a role, a wide range of modifiable influences—including obesity, physical inactivity, unhealthy dietary patterns, chronic stress, poor sleep, and exposure to endocrine-disrupting chemicals or other environmental stressors—appear to contribute substantially to this phenomenon. This narrative review synthesizes the evidence on testosterone’s physiological significance, the causes and consequences of its secular decline, and evaluates potential interventions, emphasizing lifestyle and environmental strategies (physical activity, nutrition, weight management, sleep, stress reduction, sunlight exposure) as well as pharmacological and nutraceutical options. Overall, the contemporary testosterone decline represents a complex, multifactorial public health issue requiring integrated approaches to preserve hormonal and systemic health. Full article

Alzheimer’s disease (AD) represents an increasingly severe global health challenge. Recently, the role of the gut–brain axis in AD pathogenesis has garnered significant attention. Dysbiosis of the gut microbiota can exacerbate core pathologies such as neuroinflammation, amyloid beta (Aβ) deposition, and tau hyperphosphorylation through neural, endocrine, and immune pathways. Polyphenolic compounds have emerged as a focal point in neuroprotective research owing to their pronounced anti-inflammatory and antioxidant properties. Notably, polyphenols exert effects not only by directly influencing the central nervous system (CNS) but also through indirectly modulating the composition and function of the gut microbiota, thereby impacting bidirectional gut–brain communication. This dual mechanism offers a potential avenue for their application in the prevention and treatment of AD. This review aims to compile recent research on the relationship between polyphenols and the gut microbiota. We assessed the literature from PubMed, Google Scholar, and Web of Science databases, published from the establishment of the database to 24 November 2025. The keywords used include “Polyphenols”, “Gut–brain axis”, “Gut microbiota”, “Alzheimer’s disease”, “Epigallocatechin gallate”, “Quercetin”, “Curcumin”, “Ferulic acid”, “Resveratrol”, “Anthocyanin”, “Myricetin”, “Chlorogenic acid”, etc. This review discusses the various mechanisms by which polyphenols influence AD through modulating the gut microbiota. Polyphenols and gut microbiota exhibit critical bidirectional interactions. On one hand, the bioavailability and activity of polyphenols are highly dependent on metabolic conversion by gut microbiota. On the other hand, polyphenols selectively promote the proliferation of beneficial bacteria such as bifidobacteria and lactobacilli like prebiotics, while inhibiting the growth of pathogenic bacteria. This reshapes the intestinal microecology, enhances barrier function, and regulates beneficial metabolites. Utilizing a nanotechnology-based drug delivery system, the pharmacokinetic stability and brain targeting efficacy of polyphenols can be significantly enhanced, providing innovative opportunities for the targeted prevention and management of AD. Full article

Medium- and long-chain fatty acids (MLFAs) are increasingly recognized not only as metabolic substrates but also as precursors of diverse bioactive metabolites generated through host and microbial transformations. Recent advances in analytical chemistry and microbiome research have revealed that gut microorganisms catalyze extensive modifications of dietary MLFAs—producing hydroxylated, conjugated, and keto-fatty acids with enhanced potency toward host receptors. These metabolites exhibit dual activity on classical metabolic receptors, including FFAR1/4 and PPARα/γ, as well as ectopically expressed chemosensory receptors such as olfactory receptors (ORs) and bitter taste receptors (TAS2Rs). This expanded receptor landscape establishes a previously unrecognized chemosensory–metabolic axis that integrates dietary signals, microbial metabolism, and host physiology. Microbial MLFA derivatives such as 10-hydroxyoctadecenoic acid and conjugated linoleic acid regulate incretin secretion, adipogenesis, macrophage polarization, and intestinal barrier function through coordinated activation of FFARs and PPARs. Concurrently, dicarboxylic acids such as azelaic acid activate Olfr544 to modulate lipolysis, ketogenesis, GLP-1 release, and feeding behavior. TAS2Rs also sense oxidized lipids, linking lipid metabolism to immune regulation and enteroendocrine signaling. Collectively, these pathways highlight the microbiome as a metabolic transducer that converts dietary lipids into signaling molecules influencing endocrine, immune, and gut–brain circuits. Understanding the mechanisms governing MLFA bioconversion and receptor engagement provides new opportunities for therapeutic and nutritional intervention. Targeting ORs and TAS2Rs, engineering probiotics to enhance beneficial FA-derived metabolites, and developing receptor-selective synthetic analogs represent promising strategies. Future progress will require integrative approaches combining physiology, biochemistry, metabolomics, and microbial genomics to elucidate receptor specificity and host variability. Full article

Background/Objectives: Spexin (SPX) is a bioactive peptide involved in the regulation of appetite, lipid metabolism, and glucose homeostasis. This systematic review and meta-analysis aimed to evaluate exercise-induced changes in SPX levels and their implications for metabolic health. Methods: This systematic review and meta-analysis aimed to synthesize evidence retrieved from PubMed, Web of Science, and Scopus databases, without restrictions on publication year, with the final literature search completed on 10 September 2024 and conducted in line with PRISMA 2020 reporting standards. The search strategy employed the keywords exercise, metabolic health, obesity, spexin and diabetes yielding 42 eligible records. Eligible studies included human or experimental animal populations exposed to acute or chronic exercise interventions. Exercise interventions included aerobic, resistance, combined, and high-intensity interval training protocols, with exercise intensity reported using heterogeneous metrics. The primary focus was on circulating SPX, alongside the assessment of related metabolic and endocrine parameters. Six studies satisfied the eligibility criteria and were included in the review. Results: The included studies were conducted in overweight or obese sedentary populations. Plasma SPX levels remained unchanged following acute (<3 weeks) aerobic exercise, whereas increased SPX levels were reported after chronic (≥3 weeks) exercise interventions. Elevated SPX concentrations were observed across different exercise modalities, including aerobic exercise, combined aerobic–resistance training, treadmill running, swimming, and HIIT. In addition to SPX, the included studies reported changes in metabolic and endocrine markers, including lipid-related variables, insulin-associated indices, adipokines, hormones, and selected metabolic proteins. Conclusions: This systematic review and meta-analysis indicate that exercise-related increases SPX are reported alongside changes in adiposity and metabolic–endocrine markers. Full article

Type 2 diabetes mellitus (T2DM) is an endocrine–metabolic disorder characterized by pancreatic islet dysfunction-induced hyperglycemia, which triggers hepatic injury, intestinal microbiota dysbiosis, and systemic complications. Fagopyrum tararicum seeds exhibit various biological activities, including antioxidant, hypolipidemic, and antihypertensive effects. However, there is limited research exploring how supernatants derived from the water extraction–ethanol precipitation of Fagopyrum tararicum seeds (SWEPFT) modulate the intestinal microbiota and their potential link to T2DM. This study evaluates SWEPFT’s effects on hyperglycemia and intestinal microbiota in T2DM mice. After a 4-week therapeutic period, SWEPFT markedly ameliorated hyperglycemia, as evidenced by reduced body weight (BW), fasting blood glucose (FBG), and glycated serum protein (GSP) and improved insulin sensitivity/resistance indicators (HOMA-IS/IR) and β-cell function (HOMA-β). Furthermore, the levels of both Akt1 and Slc2a2 transcription displayed notable enhancement. SWEPFT-H (high-dose SWEPFT) exhibited superior effects to SWEPFT-L (low-dose SWEPFT) in improving BW, FBG, and HOMA-IS. Moreover, SWEPFT modulated the intestinal microbiota by decreasing the Firmicutes/Bacteroidetes ratio, augmenting the proportion of Intestinimonas and Ruminiclostridium, and increasing the short-chain fatty acid content. A correlation analysis identified Candidatus_Arthromitus, Anaeroplasma, Candidatus_Stoquefichus, and Harryflintia as potential T2DM biomarkers linked to glycemic regulation. These findings elucidate SWEPFT’s critical role in microbiota modulation and hyperglycemia alleviation, providing a novel perspective for T2DM pathogenesis research and therapeutic development. Full article