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Nature and Science of Sleep 2024Obstructive sleep apnea (OSA) is a prevalent sleep breathing disorder characterized by intermittent hypoxia (IH), with continuous positive airway pressure (CPAP) as its...
BACKGROUND
Obstructive sleep apnea (OSA) is a prevalent sleep breathing disorder characterized by intermittent hypoxia (IH), with continuous positive airway pressure (CPAP) as its standard treatment. However, the effects of intermittent hypoxia/reoxygenation (IH/R) on weight regulation in obesity and its underlying mechanism remain unclear. Gut microbiota has gained attention for its strong association with various diseases. This study aims to explore the combined influence of IH and obesity on gut microbiota and to investigate the impact of reoxygenation on IH-induced alterations.
METHODS
Diet-induced obese (DIO) rats were created by 8-week high-fat diet (HFD) feeding and randomly assigned into three groups (n=15 per group): normoxia (NM), IH (6% O, 30 cycles/h, 8 h/day, 4 weeks), or hypoxia/reoxygenation (HR, 2-week IH followed by 2-week reoxygenation) management. After modeling and exposure, body weight and biochemical indicators were measured, and fecal samples were collected for 16S rRNA sequencing.
RESULTS
DIO rats in the IH group showed increased weight gain (p=0.0016) and elevated systemic inflammation, including IL-6 (p=0.0070) and leptin (p=0.0004). Moreover, IH rats exhibited greater microbial diversity (p<0.0167), and significant alterations in the microbial structure (p=0.014), notably the order , accompanied by an upregulation of bile acid metabolism predicted pathway (p=0.0043). Reoxygenation not only improved IH-exacerbated obesity, systemic inflammation, leptin resistance, and sympathetic activation, but also showed the potential to restore IH-induced microbial alterations. Elevated leptin levels were associated with (p=0.0008) and (p=0.0019), while body weight was linked to (p=0.0377). Additionally, the abundance of was negatively correlated with leptin levels (p=0.0006) and weight (p=0.0339).
CONCLUSION
IH leads to gut dysbiosis and metabolic disorders, while reoxygenation therapy demonstrates a potentially protective effect by restoring gut homeostasis and mitigating inflammation. It highlights the potential benefits of CPAP in reducing metabolic risk among obese patients with OSA.
PubMed: 38812701
DOI: 10.2147/NSS.S454297 -
Cell Death & Disease May 2024High workload-induced cellular stress can cause pancreatic islet β cell death and dysfunction, or β cell failure, a hallmark of type 2 diabetes mellitus. Thus,...
High workload-induced cellular stress can cause pancreatic islet β cell death and dysfunction, or β cell failure, a hallmark of type 2 diabetes mellitus. Thus, activation of molecular chaperones and other stress-response genes prevents β cell failure. To this end, we have shown that deletion of the glucose-regulated protein 94 (GRP94) in Pdx1 pancreatic progenitor cells led to pancreas hypoplasia and reduced β cell mass during pancreas development in mice. Here, we show that GRP94 was involved in β cell adaption and compensation (or failure) in islets from leptin receptor-deficient (db/db) mice in an age-dependent manner. GRP94-deficient cells were more susceptible to cell death induced by various diabetogenic stress conditions. We also identified a new client of GRP94, insulin-like growth factor-1 receptor (IGF-1R), a critical factor for β cell survival and function that may mediate the effect of GRP94 in the pathogenesis of diabetes. This study has identified essential functions of GRP94 in β cell failure related to diabetes.
Topics: Animals; Insulin-Secreting Cells; Mice; Receptor, IGF Type 1; Diabetes Mellitus, Type 2; Cell Death; Receptors, Leptin; Membrane Glycoproteins; Mice, Inbred C57BL; Mice, Knockout
PubMed: 38811543
DOI: 10.1038/s41419-024-06754-y -
Frontiers in Endocrinology 2024Growth Differentiation Factor 15 (GDF15) is a mitokine expressed in response to various stresses whose circulating levels increase with age and are associated with...
INTRODUCTION
Growth Differentiation Factor 15 (GDF15) is a mitokine expressed in response to various stresses whose circulating levels increase with age and are associated with numerous pathological conditions, including muscle wasting and sarcopenia. However, the use of circulating GDF15 (c-GDF15) as a biomarker of sarcopenia is still debated. Moreover, the role of GDF15 intracellular precursor, pro-GDF15, in human skeletal muscle (SM-GDF15) is not totally understood. In order to clarify these points, the association of both forms of GDF15 with parameters of muscle strength, body composition, metabolism and inflammation was investigated.
METHODS
the levels of c-GDF15 and SM-GDF15 were evaluated in plasma and muscle biopsies, respectively, of healthy subjects (HS) and patients with lower limb mobility impairment (LLMI), either young (<40 years-old) or old (>70 years-old). Other parameters included in the analysis were Isometric Quadriceps Strength (IQS), BMI, lean and fat mass percentage, thickness, as well as circulating levels of Adiponectin, Leptin, Resistin, IGF-1, Insulin, IL6, IL15 and c-PLIN2. Principal Component Analysis (PCA), Canonical Discriminant Analysis (CDA) and Receiving Operating Characteristics (ROC) analysis were performed.
RESULTS
c-GDF15 but not SM-GDF15 levels resulted associated with decreased IQS and IGF-1 levels in both HS and LLMI, while only in LLMI associated with increased levels of Resistin. Moreover, in LLMI both c-GDF15 and SM-GDF15 levels were associated with IL-6 levels, but interestingly SM-GDF15 is lower in LLMI with respect to HS. Furthermore, a discrimination of the four groups of subjects based on these parameters was possible with PCA and CDA. In particular HS, LLMI over 70 years or under 40 years of age were discriminated based on SM-GDF15, c-GDF15 and Insulin levels, respectively.
CONCLUSION
our data support the idea that c-GDF15 level could be used as a biomarker of decreased muscle mass and strength. Moreover, it is suggested that c-GDF15 has a different diagnostic significance with respect to SM-GDF15, which is likely linked to a healthy and active state.
Topics: Humans; Growth Differentiation Factor 15; Male; Biomarkers; Adult; Muscle, Skeletal; Female; Aged; Muscle Strength; Sarcopenia; Body Composition; Middle Aged
PubMed: 38808117
DOI: 10.3389/fendo.2024.1404047 -
PloS One 2024Epidemiological studies have shown that the levels of serum adipokine such as leptin and resistin are associated with the risk of developing systemic lupus erythematosus...
Epidemiological studies have shown that the levels of serum adipokine such as leptin and resistin are associated with the risk of developing systemic lupus erythematosus (SLE). Nevertheless, whether either leptin or resistin has causal impacts on the risk of SLE is still unknown. In this study, two-sample univariable MR analyses and multivariable MR analysis were performed to explore the causal relationships between adipokines and SLE. Additionally, the potential causal effects of SLE on major adipokines were evaluated using reverse MR analyses. The results of inverse-variance weighted (IVW), weighted median, weighted mode and MR‒Egger methods concordantly supported that major adipokines have no causal effects on the risk of SLE. In the multivariable MR IVW analysis with leptin and resistin as covariates, neither leptin (odds ratio (OR) = 3.093, P = 0.067) nor resistin (OR = 0.477, P = 0.311) was identified as an independent risk factor for SLE, which is in line with the univariable MR results. In conclusion, our analyses revealed no evidence to support that these three major adipokines are risk factors for SLE.
Topics: Lupus Erythematosus, Systemic; Humans; Mendelian Randomization Analysis; Resistin; Adipokines; Leptin; Risk Factors; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide
PubMed: 38805491
DOI: 10.1371/journal.pone.0301699 -
Communications Biology May 2024Studies suggest links between diabetes and gastrointestinal (GI) traits; however, their underlying biological mechanisms remain unclear. Here, we comprehensively assess...
Studies suggest links between diabetes and gastrointestinal (GI) traits; however, their underlying biological mechanisms remain unclear. Here, we comprehensively assess the genetic relationship between type 2 diabetes (T2D) and GI disorders. Our study demonstrates a significant positive global genetic correlation of T2D with peptic ulcer disease (PUD), irritable bowel syndrome (IBS), gastritis-duodenitis, gastroesophageal reflux disease (GERD), and diverticular disease, but not inflammatory bowel disease (IBD). We identify several positive local genetic correlations (negative for T2D - IBD) contributing to T2D's relationship with GI disorders. Univariable and multivariable Mendelian randomisation analyses suggest causal effects of T2D on PUD and gastritis-duodenitis and bidirectionally with GERD. Gene-based analyses reveal a gene-level genetic overlap between T2D and GI disorders and identify several shared genes reaching genome-wide significance. Pathway-based study implicates leptin (T2D - IBD), thyroid, interferon, and notch signalling (T2D - IBS), abnormal circulating calcium (T2D - PUD), cardiovascular, viral, proinflammatory and (auto)immune-mediated mechanisms in T2D and GI disorders. These findings support a risk-increasing genetic overlap between T2D and GI disorders (except IBD), implicate shared biological pathways with putative causality for certain T2D - GI pairs, and identify targets for further investigation.
Topics: Diabetes Mellitus, Type 2; Humans; Genome-Wide Association Study; Gastrointestinal Diseases; Genetic Predisposition to Disease; Mendelian Randomization Analysis
PubMed: 38802514
DOI: 10.1038/s42003-024-06333-z -
Frontiers in Oncology 2024Previous studies indicated that adipose tissue significantly influences cancer invasion and lymphatic metastasis. However, the impact of neck adipose tissue (NAT) on... (Review)
Review
Previous studies indicated that adipose tissue significantly influences cancer invasion and lymphatic metastasis. However, the impact of neck adipose tissue (NAT) on lymph node metastasis associated with head and neck cancer remains ambiguous. Here, we systematically assess the classification and measurement criteria of NAT and evaluate the association of adipose tissue and cancer-associated adipocytes with head and neck cancer. We delve into the potential mechanisms by which NAT facilitate cervical lymph node metastasis in head and neck cancer, particularly through the secretion of adipokines such as leptin, adiponectin, and Interleukin-6. Our aim is to elucidate the role of NAT in the progression and metastasis of head and neck cancer, offering new insights into prevention and treatment.
PubMed: 38800384
DOI: 10.3389/fonc.2024.1390824 -
Aging Cell May 2024Recent studies have demonstrated the remarkable potential of early life intervention strategies at influencing the course of postnatal development, thereby offering...
Recent studies have demonstrated the remarkable potential of early life intervention strategies at influencing the course of postnatal development, thereby offering exciting possibilities for enhancing longevity and improving overall health. Metformin (MF), an FDA-approved medication for type II diabetes mellitus, has recently gained attention for its promising anti-aging properties, acting as a calorie restriction mimetic, and delaying precocious puberty. Additionally, trodusquemine (MSI-1436), an investigational drug, has been shown to combat obesity and metabolic disorders by inhibiting the enzyme protein tyrosine phosphatase 1b (Ptp1b), consequently reducing hepatic lipogenesis and counteracting insulin and leptin resistance. In this study, we aimed to further explore the effects of these compounds on young, developing mice to uncover biomolecular signatures that are central to liver metabolic processes. We found that MSI-1436 more potently alters mRNA and miRNA expression in the liver compared with MF, with bioinformatic analysis suggesting that cohorts of differentially expressed miRNAs inhibit the action of phosphoinositide 3-kinase (Pi3k), protein kinase B (Akt), and mammalian target of rapamycin (Mtor) to regulate the downstream processes of de novo lipogenesis, fatty acid oxidation, very-low-density lipoprotein transport, and cholesterol biosynthesis and efflux. In summary, our study demonstrates that administering these compounds during the postnatal window metabolically reprograms the liver through induction of potent epigenetic changes in the transcriptome, potentially forestalling the onset of age-related diseases and enhancing longevity. Future studies are necessary to determine the impacts on lifespan and overall quality of life.
PubMed: 38798180
DOI: 10.1111/acel.14227 -
Nutrients May 2024Functional Gastrointestinal Disorders (FGIDs) present a higher prevalence in individuals with Neurodevelopmental Disorders (NDDs). The Stress System and the Gut-Brain...
Functional Gastrointestinal Symptoms in Children with Autism and ADHD: Profiles of Hair and Salivary Cortisol, Serum Leptin Concentrations and Externalizing/Internalizing Problems.
BACKGROUND
Functional Gastrointestinal Disorders (FGIDs) present a higher prevalence in individuals with Neurodevelopmental Disorders (NDDs). The Stress System and the Gut-Brain axis (GBA) may mediate these relations. We aimed to assess the prevalence and profile of FGIDs in a clinical sample of children with Autism Spectrum Disorder (ASD) and Attention Deficit/Hyperactivity Disorder (ADHD) compared to typically developing children (TD) as well as to investigate possible relations between stress-related biomarkers and internalizing/externalizing problems in children with NDDS.
METHODS
In total, 120 children, aged between 4 and 12 years old, formed three groups (N = 40, each): ADHD, ASD and TD. Salivary cortisol, hair cortisol and serum leptin were measured.
RESULTS
The ASD group had more FGID problems than the TD group ( = 0.001). The ADHD and ASD groups had higher total internalizing/externalizing problems than the TD group ( < 0.0001, < 0.0001, = 0.005, respectively). Children with FGIDs showed more total, internalizing and externalizing problems compared to children without FGIDs ( < 0.0001, < 0.0001, = 0.041, respectively). The ADHD group showed lower AUCg values ( < 0.0001), while the hair cortisol was higher for the TD group ( < 0.0001).
CONCLUSION
In conclusion, children with NDDs had more FGID symptoms and present higher internalizing and externalizing problems. Children with ADHD and FGIDs had more internalizing problems compared to those without FGIDs. No differences in stress-related biomarkers were shown to differentiate children with NDDs with and without FGIDs. Future prospective studies including a greater number of children may elucidate the biological pathways linking these comorbidities.
Topics: Humans; Child; Hydrocortisone; Hair; Attention Deficit Disorder with Hyperactivity; Leptin; Female; Male; Saliva; Child, Preschool; Gastrointestinal Diseases; Autism Spectrum Disorder; Biomarkers; Prevalence
PubMed: 38794776
DOI: 10.3390/nu16101538 -
Nutrients May 2024The aim of the study was to assess the impact of two lengths of Nordic walking (NW) training interventions combined with time-restricted eating (TRE) on improving...
The aim of the study was to assess the impact of two lengths of Nordic walking (NW) training interventions combined with time-restricted eating (TRE) on improving body-composition parameters, lipid profiles, and levels of selected adipokines in women with elevated body mass. Overweight and obese women ( = 55, age: 21-85) were recruited. Four groups were selected: 6 weeks (SG6, = 13) and 12 weeks intervention (SG12, = 13); and two control groups: CON6 ( = 13) and CON12 ( = 13). The training sessions took place three times a week (60 min each) and were conducted outdoors under the supervision of a professional coach. The training intensity was determined individually. The extended NW program combined with TRE induced a significant weight reduction in SG12 by 1.96 kg ( = 0.010) and fat tissue by 1.64 kg ( = 0.05). The proposed interventions did not affect LBM, TBW [kg], VFA, and lipid profile. The LDL/HDL ratio changed with a small size effect. The leptin concentration differed between groups ( = 0.006), but not over time. For resistin, the differentiating factor was time ( = 0.019), with lower results observed after the intervention. The change in leptin concentration was negatively correlated with its baseline concentration ( = 0.025). Extended to 12 weeks, this intervention allows for an improvement in body composition. Neither 6 nor 12 weeks of training and fasting affected the lipoprotein profile. It is, therefore, indicated to recommend prolonged training protocols and to inform patients that beneficial effects will be seen only after prolonged use of training and time-restricted eating.
Topics: Humans; Female; Body Composition; Middle Aged; Adult; Walking; Aged; Obesity; Aged, 80 and over; Young Adult; Overweight; Leptin; Time Factors; Weight Loss; Exercise Therapy; Lipids; Fasting; Resistin
PubMed: 38794651
DOI: 10.3390/nu16101413 -
Journal of Clinical Medicine May 2024Many studies have addressed the sex differences in patients with psoriatic arthritis, although these are aimed more at describing the phenotype than at investigating...
Many studies have addressed the sex differences in patients with psoriatic arthritis, although these are aimed more at describing the phenotype than at investigating the causes underlying these differences. The aims of our study were to assess the presence of clinical features in relation to sex, and to measure the effect on disease activity of different comorbidities in each sex. This was a cross-sectional study in which the following factors were measured: the clinical features of the disease, disease activity, the physical function and the disease impact. We measured serum leptin levels, to eliminate the effect of obesity on leptin levels, and a leptin/BMI ratio was calculated. The comorbid conditions evaluated included anxiety and depression, and sleep quality. A total of 203 patients participated in this study. The mean age was 54.6 ± 11.3, and 46.8% of the patients were women. Women less frequently presented axial involvement (8% vs. 28%; < 0.001) and more commonly had enthesitis (2 vs. 0.3; < 0.001). They also had higher DAPSA (16.4 vs. 13.4; < 0.001) and PsAID12 scores (4.1 vs. 2.9; < 0.001), worse HAQ results (0.8 vs. 0.5; < 0.001), and greater FACIT-F scores (32.7 vs. 38.1; < 0.001). As for the comorbid conditions, women presented a higher leptin/BMI ratio (0.8 vs. 0.2; < 0.001), higher levels of HADS-A (6.9 vs. 4.7; < 0.001) and HADS-D (4.9 vs. 3.4; < 0.001), and poorer ISI (9.3 vs. 7.0; < 0.001). By sex, pain affecting women was associated with the leptin/BMI ratio (β: 0.29; < 0.004; 95%CI: 0.3-1.6) and sleep quality (β: 0.31; < 0.004; 95%CI: 0.04-0.25; R: 0.26). The leptin/BMI ratio was not associated with pain in men ( = 0.46). Sex was associated with several clinical manifestations. Leptin/BMI ratio levels were associated with pain in women, but not in men.
PubMed: 38792501
DOI: 10.3390/jcm13102959