Search Results (338)

Obstructive sleep apnea (OSA) is a prevalent disorder linked to metabolic complications such as diabetes and cardiovascular disease. By fragmenting normal sleep architecture, OSA perturbs the growth hormone/insulin-like growth factor (GH/IGF) axis and alters circulating levels of IGF-binding proteins (IGFBPs). A prior clinical observation of elevated IGFBP4 in OSA patients motivated the present investigation in a controlled animal model. Building on the previously reported protocol, OSA was induced in male C57BL/6 mice (9–12 weeks old) through intralingual injection of polytetrafluoroethylene (PTFE), producing tongue hypertrophy, intermittent airway obstruction, and hypoxemia. After 8–10 weeks, the study assessed (1) hypoxia biomarkers—including HIF-1α and VEGF expression—and (2) neurobehavioral outcomes in anxiety and cognition using the open-field and novel object recognition tests. PTFE-treated mice exhibited a significant increase in circulating IGFBP4 versus both baseline and control groups. Hepatic Igfbp4 mRNA was also upregulated. Behaviorally, PTFE mice displayed heightened anxiety-like behavior and impaired novel object recognition, paralleling cognitive deficits reported in human OSA. These findings validate the PTFE-induced model as a tool for studying OSA-related hypoxia and neurocognitive dysfunction, and they underscore IGFBP4 as a promising biomarker and potential mediator of OSA’s systemic effects. Full article

Fecal microbiota transplantation (FMT) promotes growth performance and intestinal development in yellow-feathered broilers, but whether the virome and metabolites contribute to its growth-promoting effect remains unclear. This study removed the microbiota from FMT filtrate using a 0.45 μm filter membrane, retaining the virome and metabolites to perform fecal virome transplantation (FVT), aiming to investigate its regulatory role in broiler growth. Healthy yellow-feathered broilers with high body weights (top 10% of the population) were used as FVT donors. Ninety-six 8-day-old healthy male yellow-feathered broilers (95.67 ± 3.31 g) served as FVT recipients. Recipient chickens were randomly assigned to a control group and an FVT group. The control group was gavaged with 0.5 mL of normal saline daily, while the FVT group was gavaged with 0.5 mL of FVT solution daily. Growth performance, immune and antioxidant capacity, intestinal development and related gene expression, and microbial diversity were measured. The results showed that FVT improved the feed utilization rate of broilers (the feed conversion ratio decreased by 3%; p < 0.05), significantly increased jejunal length (21%), villus height (69%), and crypt depth (84%) (p < 0.05), and regulated the jejunal barrier: insulin-like growth factor-1 (IGF-1) (2.5 times) and Mucin 2 (MUC2) (63 times) were significantly upregulated (p < 0.05). FVT increased the abundance of beneficial bacteria Lactobacillales. However, negative effects were also observed: Immunoglobulin A (IgA), Immunoglobulin G (IgG), Immunoglobulin M (IgM), Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-α), and Interferon-gamma (IFN-γ) in broilers were significantly upregulated (p < 0.05), indicating immune system overactivation. Duodenal barrier-related genes Mucin 2 (MUC2), Occludin (OCLN), Claudin (CLDN1), and metabolism-related genes solute carrier family 5 member 1 (SLC5A1) and solute carrier family 7 member 9 (SLC7A9) were significantly downregulated (p < 0.05). The results of this trial demonstrate that, besides the microbiota, the gut virome and metabolites are also functional components contributing to the growth-promoting effect of FMT. The differential responses in the duodenum and jejunum reveal spatial heterogeneity and dual effects of FVT on the intestine. The negative effects limit the application of FMT/FVT. Identifying the primary functional components of FMT/FVT to develop safe and targeted microbial preparations is one potential solution. Full article

Endometriosis is a disorder characterized by the presence of endometrial tissue outside the uterus, leading to dyspareunia, chronic pelvic pain, dysuria, and infertility. The latter has been related to implantation failure associated with alterations in decidualization, a process regulated by sex hormones such as progesterone. Membrane progesterone receptor β (mPRβ) exhibits a lower expression in endometriotic tissues than in normal endometrial ones. However, the role of mPRβ in decidualization is unknown. This work aimed to investigate whether mPRβ plays a role in the decidualization of endometrial stromal cells (ESCs) derived from women with and without endometriosis. The mPR agonist OrgOD-2 induced the gene expression of key decidualization markers (insulin-like growth factor binding protein 1, prolactin, transcription factor heart and neural crest derivatives-expressed transcript 2, and fork-head transcription factor) in healthy ESCs, eutopic (uterine cavity), and ectopic (outside of the uterine cavity) ESCs from women with endometriosis. Notably, the expression of the decidualization markers was lower in endometriotic cells than in healthy endometrial ones. An siRNA mediated knockdown of mPRβ reduced the expression of decidualization-associated genes in ESCs treated with a decidualization stimuli, regardless of whether cells were derived from healthy women or those with endometriosis. Our data suggest that progesterone, through mPRβ activation, regulates the decidualization process in endometrial stromal cells from women with and without endometriosis. Full article

This experiment examined whether multiparous sows fed a diet lower in energy and lysine at a reduced feed allowance would still mobilise fat and (or) protein to support piglet growth and negatively impact subsequent reproductive performance. A total of 152 multiparous sows was allocated in a 2 × 2 factorial design with the respective factors being diet type fed in lactation (gestation, 13.0 MJ digestible energy (DE)/kg, 0.42 g standardised ileal digestible (SID) lysine/MJ DE; or lactation, 14.3 MJ DE/kg, 0.62 g SID lysine/MJ DE) and feed allowance (ad libitum or 7.5 kg/d, ~15% reduction on ad libitum intake). Body composition was estimated on the day after farrowing (day 2) and at weaning (day 21). Blood was collected on days 2, 21 and at standing heat, for the analysis of insulin and insulin-like growth factor 1 (IGF-1). Diet type did not alter (p > 0.05) bodyweight or P2 backfat depth change in lactation, estimated body fat and protein changes, litter growth, or subsequent total piglets born. Ad libitum-fed sows showed a significant gain in girth compared to sows offered 7.5 kg/d (2.9 versus −0.4 mm, p = 0.015) and had a tendency for a shorter wean-to-service interval (p < 0.10). Sows fed the lactation diet had higher insulin concentrations at weaning (p < 0.05), but levels were the same (p > 0.10) by heat detection; IGF-1 concentrations remained unaffected. These data indicate that imposing a calculated negative energy and lysine balance on lactating sows had a limited impact on lactation or subsequent reproductive performance, supporting the notion that the modern sow may be more resilient to nutritional impositions than has been historically reported. Full article

Neurotrophins and inflammatory mediators are known to influence endometrial function, but their interplay in luminal epithelial cells remains poorly characterized. In this study, sheep endometrial luminal epithelial cells (SELECs) were treated with nerve growth factor (NGF), lipopolysaccharide (LPS), or both, and the effects on gene expression and prostaglandin secretion were evaluated. NGF stimulation alone induced a clear transcriptional activation of NGF, neurotrophic receptor tyrosine kinase 1 (NTRK1), p75 neurotrophin receptor (p75NTR), cyclooxygenase 2 (COX2), and steroidogenic acute regulatory protein (STAR). LPS treatment selectively increased Toll-like receptor 4 (TLR4), COX2, and insulin-like growth factor binding protein 6 (IGFBP6). Combined NGF and LPS treatment did not enhance the transcriptional response beyond that induced by NGF alone, except for STAR. However, co-treatment resulted in a modest increase in prostaglandin production, particularly prostaglandin F2α (PGF2α), but not prostaglandin E2 (PGE2), compared to single treatments, suggesting a possible post-transcriptional modulation rather than a transcriptional synergy. These findings indicate that NGF acts as the primary transcriptional driver in SELECs, while LPS contributes selectively and may enhance prostaglandin output. The observed increase in prostaglandin production may involve post-transcriptional mechanisms, although this remains to be confirmed. Full article

Insulin-like growth factor-binding protein-3 (IGFBP-3) plays a vital role in cellular growth, development, and survival. Incorporating IGFBP-3 into baseline prognostic evaluations may enhance the prediction of mortality in patients with sepsis. In this study, serum levels of IGFBP-3, C-reactive protein, procalcitonin, lactate, interleukin-6, and mid-regional pro-adrenomedullin were measured upon admission to the internal medicine unit (IMU) in 139 patients with microbiologically confirmed sepsis. The objectives were as follows: (1) to classify septic patient phenotypes based on optimal thresholds of independent prognostic biomarkers and (2) to evaluate whether these biomarkers improve the predictive accuracy of a clinical model (Model 1), which includes the clinical predictors of 1-year mortality. Age, sequential organ failure assessment (SOFA) score, multiple sources of infection, and IGFBP-3 levels independently predicted 1-year mortality. Patients with IGFBP-3 levels below 10.64 had significantly lower median body temperature (p = 0.008), reduced lymphocyte count (p = 0.001), and higher 1-year mortality (p < 0.001). Model 1 included age, SOFA score, and the presence of multiple sources of sepsis as predictor variables. Model 2 incorporated the same variables as Model 1, with the addition of IGFBP-3 levels. When comparing their prognostic performance, Model 2 demonstrated superior predictive accuracy for mortality at 60, 90, and 365 days following admission to the IMU. Low IGFBP-3 levels at IMU admission are strongly associated with worse outcomes in septic patients, supporting its potential use as a prognostic biomarker. Full article

Obesity is considered a global pandemic. In Mexico, 7/10 adults, 4/10 adolescents, and 1/3 children are overweight or obese, and it is estimated that 90% of cases of type 2 diabetes (T2D) are attributable to these pathologies. Visceral adipose tissue (VAT) presents increased lipolysis, lower insulin sensitivity, and greater metabolic alterations. Glucagon-like peptide-1 (GLP-1) is a polypeptide incretin hormone that stimulates insulin secretion dependent on the amount of oral glucose consumed, reduces plasma glucagon concentrations, slows gastric emptying, suppresses appetite, improves insulin synthesis and secretion, and increases the sensitivity of β cells to glucose. Liraglutide is a synthetic GLP-1 analog that reduces VAT and improves the expression of Glucose transporter receptor type 4 (GLUT 4R), Mitogen-activated protein (MAP kinases), decreases Fibroblast growth factor type β (TGF-β), reactivates the peroxisome proliferator-activated receptor type ɣ (PPAR-ɣ) pathway, and decreases chronic inflammation. Currently, there are many studies that explain the decrease in VAT with these medications, but there are no studies that compare the decrease in patients with obesity and prediabetes vs. obesity and type 2 diabetes to know which population obtains a greater benefit from treatment with this pharmacological group; this is the reason for this study. The primary objective was to compare the difference in the determination of visceral adipose tissue in people with obesity and type 2 diabetes vs. obesity and prediabetes treated with liraglutide. Methods: A quasi-experimental, analytical, prolective, non-randomized, non-blinded study was conducted over a period of 6 months in a tertiary care center. A total of 36 participants were divided into two arms; group 1 (G1: Obesity and prediabetes) and group 2 (G2: Obesity and type 2 diabetes) for 6 months. Inclusion criteria: men and women ≥18 years with type 2 diabetes, prediabetes, and obesity. Exclusion criteria: Glomerular filtration rate (GFR) < 60 mL/min/1.73 m² elevated transaminases (>5 times the upper limit of normal), and use of non-weight-modifying antidiabetic agents. Conclusions: No statistically significant difference was found in the decrease in visceral adipose tissue when comparing G1 (OB and PD) with G2 (OB and T2D). When comparing intragroup in G2 (OB and T2D), greater weight loss was found [(−3.78 kg; p = 0.012) vs. (−3.78 kg; p = 0.012)], as well differences in waist circumference [(−3.9 cm; p = 0.049) vs. (−3.09 cm; p = 0.017)], and glucose levels [(−1.75 mmol/L; p = 0.002) vs. (−0.56 mmol/L; p = 0.002)], A1c% [(−1.15%; p = 0.001) vs. (−0.5%; p = 0.000)]. Full article

Skeletal muscle, traditionally recognized for its motor function, has emerged as a key endocrine organ involved in metabolic regulation and interorgan communication. This narrative review addresses the dual role of muscle as a target tissue for classical hormones—such as growth hormone (GH), insulin-like growth factor type 1 (IGF-1), thyroid hormones, and sex steroids—and as a source of myokines, bioactive peptides released in response to muscle contraction that exert autocrine, paracrine, and endocrine effects. Several relevant myokines are discussed, such as irisin and Metrnl-like myokines (Metrnl), which mediate exercise-associated metabolic benefits, including improved insulin sensitivity, induction of thermogenesis in adipose tissue, and immunometabolic modulations. It also examines how muscle endocrine dysfunction, caused by chronic inflammation, hormone resistance, or sedentary lifestyle, contributes to the development and progression of metabolic diseases such as obesity, type 2 diabetes, and sarcopenia, highlighting the importance of muscle mass in the prognosis of these pathologies. Finally, the therapeutic potential of interventions aimed at preserving or enhancing muscle function—through physical exercise, hormone therapy and anabolic agents—is highlighted, together with the growing research on myokines as biomarkers and pharmacological targets. This review expands the understanding of muscle in endocrinology, proposing an integrative approach that recognizes its central role in metabolic health and its potential to innovate the clinical management of endocrine–metabolic diseases. Full article

Insulin-like growth factor-binding protein 6 (IGFBP-6) is primarily recognized for its inhibitory effects on insulin-like growth factor 2 (IGF-2), regulating processes such as cell proliferation, differentiation, and survival. However, recent studies have revealed that IGFBP-6 also participates in a range of IGF-independent activities, notably in redox biology, immune regulation, and fibrosis. These IGF-independent actions involve interactions with redox-sensitive signaling pathways that influence mitochondrial metabolism, neutrophil function, and fibroblast activity, all of which are central to redox-dependent processes in inflammation and fibrosis. Despite these insights, the precise mechanisms by which IGFBP-6 modulates redox signaling remain largely unexplored. This review examines the growing understanding of IGFBP-6 beyond its classical role as an IGF-binding protein, with a focus on its involvement in redox homeostasis. By exploring these emerging roles, we aim to elucidate how IGFBP-6 contributes to redox homeostasis and to assess its potential as a therapeutic target in oxidative stress-related diseases, including fibrosis, cancer, and immune dysfunction. Full article

Background: Preeclampsia (PE) is a deadly obstetric complication in pregnant women leading to escalated rates of maternal and fetal mortality. Current research indicates that inadequate invasion of extravillous trophoblasts (EVTs) is a primary factor associated with the pathogenesis of PE. Insulin-like growth factor binding protein 2 (IGFBP2) plays a significant role in promoting cell migration, invasion, and angiogenesis. Researchers aim to investigate the clinical significance and elucidate the molecular mechanisms of IGFBP2 in the pathogenesis of preeclampsia. Methods: This study included 40 pregnant women categorized into 20 PE patients and 20 healthy controls. Expression levels of the mRNA were quantified using real-time quantitative polymerase chain reaction (qRT-PCR), and protein levels were assessed through Western blotting and immunofluorescence techniques. Moreover, the gain- and loss-of-function assays were conducted in human trophoblast cell line HTR-8/SVneo, and cellular models exhibiting overexpression and the knockdown of IGFBP2 were established. The proliferation, migration, and invasion of HTR-8/Svneo cells were determined using CCK8, wound-healing, and transwell assays, respectively. Results: The IGFBP2 was significantly downregulated, and the EMT was suppressed in the placental tissues of the PE patients. Functional experiments demonstrated that IGFBP2 enhanced the proliferation, invasion, and EMT of trophoblast cells activated through the PI3K/AKT signaling pathway. Conclusion: Our findings indicated that IGFBP2 enhances the proliferation, invasion, and EMT of trophoblast cells by activating the PI3K/AKT signaling pathway, serving as a potential therapeutic target in PE patients. Full article

Genomic imprinting is critical for mammalian development, but its regulation varies across species. The insulin-like growth factor 2 receptor (IGF2R), which is a maternally expressed imprinted gene critical for cell proliferation and differentiation, as well as embryonic and placental development, is classically regulated by differentially methylated regions (DMRs) and lncRNA-Airn in mice. However, studies on this in equus are scarce, especially in terms of mechanistic studies. In the present study, heart, liver, spleen, lung, kidney, brain, and muscle samples were obtained from horses, donkeys, and hybrids, and gene expression and imprinting state were tested to investigate the imprinting regulation of Igf2r in these animals. Bisulfite sequencing combined with an allele-specific expression analysis revealed a tissue-specific loss of imprinting in the mule liver and hybrid brain tissues. Strikingly, we found that the maternal-specific expression of equine Igf2r did not rely on the canonical DMRs or lncRNA-Airn. Surprisingly, DNA methylation of a specific region called CpG island 2 (CpGI2) in the Igf2r promoter showed cis-acting inheritance, meaning that the DNA methylation patterns of the parental alleles are retained in hybrid tissues. Notably, the DNA methylation of CpGI2 correlated negatively with Igf2r expression in the spleen (R² = 0.8797, p = 6.46 × 10⁻⁶), lung (R² = 0.8569, p = 1.57 × 10⁻⁵), and kidney (R² = 0.8650, p = 3.85 × 10⁻⁶). Our findings suggest that imprinting may work differently in other species. This study provides a framework for understanding imprinting diversity in hybrids and shows that equine hybrids can be used to study how epigenetic inheritance works. Full article

The insulin-like growth factor (IGF) system has significance for poststroke outcomes. Previously, we reported that low serum IGF-II (s-IGF-II) in the acute phase is associated with poststroke mortality, and that IGF-II is lower among males. Given the known interactions of the IGF system and estrogen receptor signaling, s-IGF-II may have sex-specific effects. In this study, we conducted a secondary analysis of sex differences in s-IGF-II and poststroke functional outcomes and mortality after ischemic stroke (IS) in the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS, males; n = 315, females; n = 177). Functional outcomes were assessed using the modified Rankin scale (mRS) at 3 months and 2 years poststroke. Survival was recorded for 7 years or until death. Males in the lowest quintile of acute s-IGF-II had a higher poststroke mortality, with a crude hazard ratio [HR] of 2.52 (95% confidence interval [CI]) 1.59–3.99) and an adjusted HR of 1.83 (95% CI 1.09–3.06). No corresponding significant association was observed in females. Although acute s-IGF-II was crudely associated with poor functional outcomes among males after 3 months and 2 years, these associations were not independent of initial stroke severity in adjusted models. In conclusion, low levels of acute s-IGF-II are linked with poststroke mortality among males, but not significantly in females. Further studies are, however, warranted with sex hormone analysis, consideration of specific cause of death, and more females. Full article

Background/Objectives: Metabolic syndrome (MetS) is a complex, multifaceted disorder with significant socioeconomic and public health consequences, increasingly acknowledged as a global epidemic. Fibroblast growth factor 21 (FGF-21) is known to play a vital role in metabolic regulation; however, the precise roles and interactions of free fatty acids (FFAs) and insulin in influencing FGF-21 activity under both normal and pathological conditions are not yet fully understood. Meteorin-like protein (Metrnl) is a newly identified adipokine that appears to have the potential to regulate metabolic inflammation, which is a critical pathological factor in obesity and insulin resistance. Additionally, nesfatin-1, which is widely expressed in both central and peripheral tissues, is thought to be involved in various physiological functions beyond appetite control, such as glucose homeostasis, stress response, and cardiovascular health. Recent studies have indicated that sortilin may play a role in the pathophysiology of several metabolic disorders, including type 2 diabetes mellitus. Methods: This investigation was a cross-sectional study involving 200 individuals with obesity, which included both metabolically healthy obese participants and those experiencing obesity along with glycemic disorders. Serum levels of FGF-21, sortilin, Metrnl, and nesfatin-1 were measured using standardized enzyme-linked immunosorbent assay (ELISA) techniques. Results: The results indicated that FGF-21 levels were significantly elevated in patients with metabolic syndrome (p < 0.001), as well as those with insulin resistance (p = 0.009) and dyslipidemia (p = 0.03). Serum Metrnl levels were notably elevated in individuals meeting the criteria for insulin resistance, with a statistical significance of p < 0.001. Additionally, patients experiencing carbohydrate metabolism disorders exhibited significantly higher serum sortilin levels compared to those with normal blood glucose levels, with a p-value of 0.003. Conclusions: This research highlights FGF-21, Metrnl, nesfatin-1, and sortilin as potential biomarkers involved in the development of critical aspects of metabolic syndrome. Full article

This study was conducted to investigate the effects of replacing fish meal with either whole-fat or defatted krill powder on the growth, body color, immunity, and related gene expression of red–white koi carp. A total of 630 red–white koi carp with an initial body mass of 13.5 ± 0.05 g were randomly divided into seven groups with three replicates per group and 30 fish per replicate. The control group was fed a basic diet (C0). The other six diets were supplemented with different levels of whole krill meal or defatted krill meal as replacements (10% whole fat, 20% whole fat, 30% whole fat, 10% defatted, 20% defatted, and 30% defatted) in the experimental groups, named W10, W20, W30, D10, D20, and D30, respectively, for a total duration of 60 days. The growth, body color, immunity and gene expression indexes were measured in the koi after completion. The results indicate the following. (1) Compared with C0, the experimental groups of koi showed a significant increase in the specific growth rate (SGR) (p < 0.05), while the hepatosomatic index (HSI) and viscerosomatic ratio (VSI) decreased. Additionally, there was a significant increase in the relative expression level of insulin-like growth factor (IGF-1) in both the liver and muscle (p < 0.05). (2) The experimental groups of koi carp exhibited a significant increase in the carotenoid content in the scales and skin, as well as an elevated relative expression level of the tyrosinase (TYR) gene in the muscle (p < 0.05). (3) The lysozyme (LZM) and superoxide dismutase (SOD) activities were significantly increased in the experimental groups compared to C0 (p < 0.05). Additionally, the SOD activity was significantly higher in the defatted groups than in the whole-fat groups (p < 0.05). Furthermore, the liver alkaline phosphatase (AKP) activity was significantly lower in the D20 and D30 groups compared to the other five groups. (4) The expression level of LPL was significantly lower in the liver and muscle of the whole-fat group compared to the defatted group (p < 0.05). Tissue section observation revealed that the hepatocytes in the W20 and W30 groups exhibited a reduced size and an increased lipid droplet count, while the vacuolar degeneration of the hepatocytes increased in the D30 group. In conclusion, replacing fish meal with whole-fat or defatted krill powder or defatted Antarctic krill meal significantly improves the growth performance, body color, and immunity of red–white koi carp. However, excessive addition of krill meal can easily cause liver damage. The recommended replacement level for whole krill powder is 20% to 30%, while defatted krill powder should be replaced at a level of 10% to 20%. Full article