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High-fat diet increase proinflammatory cytokines in primary glial culture. (A) Quantitative real-time PCR data show the mean (±SEM) expression levels compared to the Sham control group for TNFα mRNA. (B) Quantitative real-time PCR data show the mean (±SEM) expression levels compared to the Sham control group for IL-1β mRNA. All data are normalized with corresponding β-actin values. Statistical significance is based on ANOVA followed by Bonferroni. * P ≤0.05 between diet groups; ** P ≤0.05 between hormone groups; N ≥6.
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Background
Low testosterone and obesity are independent risk factors for dysfunction of the nervous system including neurodegenerative disorders such as Alzheimer¿s disease (AD). In this study, we investigate the independent and cooperative interactions of testosterone and diet-induced obesity on metabolic, inflammatory, and neural health indices i...
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Context 1
... <0.001) and not hormone (F 2,12 = 2.1; P = 0.17) on mRNA levels of TNFα in comparing the levels in the glial cultures from both diet groups. However, there was a significant decrease in TNFα mRNA levels with testosterone treatment in the high- fat animals (P <0.05) ( Figure 3A). IL-1β mRNA levels were also significantly affected by diet (F 1,12 = 49.5; ...
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... It is believed that insulin is a nutrient that regulates neuronal development and proliferation. The peripheral nervous system regulates the discharge and storage of urine; the urethral sphincter and the bladder's detrusor muscle cooperate to carry out this function; IR may harm these peripheral nerves and muscles, resulting in incontinence [37,38]. Insulin, on the other hand, modulates oxidative capacity and mitochondrial metabolism via PI3K/ Akt signaling [39,40]. ...
Background
Postmenopausal women are more susceptible to stress urinary incontinence (SUI), and insulin resistance (IR) is closely related to SUI. The triglyceride-glucose (TyG) index is an efficient metric for assessing IR. Investigating whether TyG index and its correlation indexes were correlated with SUI in postmenopausal women was the aim of this research.
Methods
Data from 2,132 postmenopausal women from the National Health and Nutrition Examination Survey (NHANES) were included in the study for analysis. Weighted multiple logistic regression was used to evaluate the correlation between the TyG index and its correlation indexes and SUI. The nonlinear correlation between the TyG correlation indexes and SUI, as well as the diagnostic efficacy for SUI, was investigated using the smooth curve approach and receiver operating characteristics. Through detailed subgroup analysis, the stability and generalization of the results are confirmed.
Results
Of the 26.87 million, 13.63 million, or 50.73%, suffered from SUI. The prevalence of SUI was significantly higher in the fourth quartile of TyG-BMI (OR = 1.93, 95% CI 1.13–2.84), TyG-WC (OR = 1.76, 95% CI 1.23–2.51), and TyG-WHtR (OR = 1.81, 95% CI 1.28–2.55) compared to the first quartile. Among the three models, TyG-WHtR always maintained a more significant correlation with SUI (Model 1:OR = 1.30;Model 2:OR = 1.33; Model 3:OR = 1.24). Smooth curve fitting results showed that TyG correlation indexes were not linearly correlated with SUI (P > 0.05). Subgroup analysis further confirmed the reliability and applicability of the results. TyG-BMI had the greatest diagnostic performance for SUI out of the four markers.
Conclusions
In comparison to TyG, TyG correlation indexes showed a more significant correlation with SUI among postmenopausal women in US, with TyG-BMI showing the best diagnostic effectiveness.
... Specifically, abdominal fat accumulation may stimulate the sympathetic nervous system, leading to hyperactivity of the detrusor muscle and causing OAB symptoms [36]. Additionally, obesity may affect the pelvic nervous system, altering bladder sensory and motor functions [37,38]. ...
Background
The link between regional body fat distribution and overactive bladder (OAB) in prior epidemiological research has been uncertain. Our objective is to assess the relationship between increased regional body fat and the prevalence of OAB.
Methods
Within this analysis, 8,084 individuals aged 20 years and older were selected from NHANES surveys conducted from 2011 to 2018. The evaluation of OAB symptoms utilized the overactive bladder symptom score (OABSS). Fat mass (FM) across various regions was quantified employing dual-energy X-ray absorptiometry, which assessed total FM, trunk FM, arm FM, and leg FM. The fat mass index (FMI) was calculated as the ratio of fat mass (kg) to the square of height (meters). Data weighting was performed in accordance with analysis guidelines. A linear logistic regression model was employed to assess the correlation between regional FMI and the occurrence of OAB. Stratified analyses were also conducted.
Results
The study found significant associations between total FMI and limb FMI with OAB. After adjusting for all variables in the analysis, higher total FMI (OR = 1.07, 95% CI = 1.02–1.12) was linked to an increased risk of OAB. Trunk FMI (OR = 1.12, 95% CI = 1.03–1.22), arm FMI (OR = 1.59, 95% CI = 1.20–2.10), and leg FMI (OR = 1.12, 95% CI = 1.01–1.25) demonstrated significant correlations with OAB. The weighted associations between total FMI and limb FMI with OAB incidence showed no significant differences among most subgroups.
Conclusions
The data indicates a correlation between higher regional FMI and increased OAB risk across different populations.
... An alternative wintering strategy, hibernation, involves substantial metabolic changes (19,20) regulated by a genetic toolkit of metabolic pathways, circadian rhythms, and thermogenesis (21). Many of the metabolic changes of wintering strategies are related to the metabolic dysregulation also observed in human neurodegenerative diseases (22)(23)(24)(25). As wintering survival strategies are a continuum of conserved processes (26), brain and metabolic alteration in DP could resemble mechanisms of hibernation. ...
Contrasting almost all other mammalian wintering strategies, Eurasian common shrews, Sorex araneus , endure winter by shrinking their brain, skull, and most organs, only to then regrow to breeding size the following spring. How such tiny mammals achieve this unique brain size plasticity while maintaining activity through the winter remains unknown. To discover potential adaptations underlying this trait, we analyzed seasonal differential expression in the shrew hypothalamus, a brain region that both regulates metabolic homeostasis and drastically changes size and compared hypothalamus expression across species. We discovered seasonal variation in suites of genes involved in energy homeostasis and apoptosis, shrew-specific upregulation of genes involved in the development of the hypothalamic blood brain barrier and calcium signaling, as well as overlapping seasonal and comparative gene expression divergence in genes implicated in the development and progression of human neurological and metabolic disorders, including CCDC22 , FAM57B , and GPR3 . With high metabolic rates and facing harsh winter conditions, Sorex araneus have evolved both adaptive and plastic mechanisms to sense and regulate its energy budget. Many of these expression changes mirrored those identified in human neurological and metabolic disease, highlighting the interactions between metabolic homeostasis, brain size plasticity, and longevity.
... [32] This occurs as testosterone prevents nuclear translocation of NF-κB (which induces the expression of various proinflammatory genes encoding cytokines and chemokines), blunts the increased production of proinflammatory mediators caused by interferon-γ (INF-γ), [32] decreases prostaglandin E2 (PGE2) production and prevents maturation of type-1 and type-17 helper T cells. [33] Testosterone also modulates inflammation by altering leukocyte infiltration, [34][35][36] preventing the deleterious effect of interleukin-1β (IL-1β) and IL-6 on cartilage and bone, attenuating the expression of vascular cell adhesion molecules, [7] and by promoting angiogenesis which assists in the resolution of inflammation and wound healing. [36] Some studies suggest that testosterone has a proinflammatory effect. ...
Background
Testosterone is an anabolic and androgenic steroid hormone therapeutically used to produce male sex characteristics. It has also been shown to have a modulating effect on proinflammatory biomarkers. Critical illness is characterised by a proinflammatory and catabolic state and is accompanied by altered testosterone production, which may persist into the recovery phase. Testosterone may, therefore be a potential therapeutic option in critical illness. This paper reviews normal testosterone physiology, and the changes seen during critical illness and systematically reviews testosterone therapy during both the acute and chronic phases of critical illness.
Contribution of the study
This article explains the pathophysiology of testosterone during critical illness and explores the therapeutic value of testosterone in the management of critically ill patients.
... [2] These diseases include cardiovascular diseases, [3] obesity, diabetes, [4] dyslipidemia, [5] and degenerative diseases. [6] Currently, pharmaceutical treatments for inflammation in clinical practice include steroids, ...
The rising prevalence and detrimental impact of inflammatory diseases have spurred the exploration of novel therapeutic approaches to tackle these conditions. Fuzi, lateral root of Aconitum carmichaelii Debx. has been used as a traditional Chinese medicine (TCM) for the treatment of inflammatory diseases for a long time. This article provides a comprehensive review of the medicinal applications, anti-inflammatory constituents, analytical techniques for detecting anti-inflammatory components, molecular mechanisms, and anti-inflammatory effects of Fuzi and its formulas. The information on Fuzi was collected from a variety of resources including classical works on Chinese herbal medicine, scientific databases (PubMed, Google Scholar, ACS, Web of Science, Science Direct, CNKI), TCMSP, NCBI, PubChem databases and others. About 122 compounds were isolated and identified from Fuzi, with alkaloids constituting the primary constituents that demonstrate potent anti-inflammatory activity. Specifically, among the identified compounds, there was one C-18 type, nineteen C-19 type, four C-20 type diterpenoid alkaloids, one other alkaloid, and 6 non-alkaloid constituents, all of which exhibited noteworthy anti-inflammatory and pain-alleviating properties in both in vivo and in vitro models of inflammation. These effects were mainly attributed to the reduction of pro-inflammatory cytokines, including IL-1, TNF-α, NO, IL-Iβ, and IL-6, as well as the inhibition of MAPK, NF-κB or PI3K/Akt signaling pathways, which effectively suppressed the inflammatory response and alleviated pain. Additionally, the anti-inflammatory effects were also achieved through the regulation of TLR4 expression and its downstream factors, or by modulating the homeostasis of the gut microbiota.
... Analyzed from a possible molecular mechanism standpoint, potential factors related to brain changes and cognition may be explained by the release of different secretory factors from different fat deposits (55,56). These different fat deposits release different secreted factors that can cross the blood-brain barrier (BBB) and cause damage, increase cognitive impairment and accelerate AD progression (55). ...
... Analyzed from a possible molecular mechanism standpoint, potential factors related to brain changes and cognition may be explained by the release of different secretory factors from different fat deposits (55,56). These different fat deposits release different secreted factors that can cross the blood-brain barrier (BBB) and cause damage, increase cognitive impairment and accelerate AD progression (55). Pro-inflammatory factors secreted by adipocytes, such as leptin, IL-6 and TNF-α, can cross the BBB and lead to neuroinflammation, thus playing a role in cognitive impairment and AD (56). ...
... Most of these changes occur in the volume of different brain regions and the level of cortical proteins. This series of changes points to commonalities between metabolic diseases and cognitive changes in brain injury (13,19,20,41,(55)(56)(57). Another study found that long-term high-sugar and high-fat diets can induce metabolic syndrome in experimental animals, and their brain tissue can exhibit typical characteristic changes of AD (99). ...
Alzheimer's disease (AD) is a type of neurodegenerative disease characterized by cognitive impairment that is aggravated with age. The pathological manifestations include extracellular amyloid deposition, intracellular neurofibrillary tangles and loss of neurons. As the world population ages, the incidence of AD continues to increase, not only posing a significant threat to the well-being and health of individuals but also bringing a heavy burden to the social economy. There is epidemiological evidence suggesting a link between AD and metabolic diseases, which share pathological similarities. This potential link would deserve further consideration; however, the pathogenesis and therapeutic efficacy of AD remain to be further explored. The complex pathogenesis and pathological changes of AD pose a great challenge to the choice of experimental animal models. To understand the role of metabolic diseases in the development of AD and the potential use of drugs for metabolic diseases, the present article reviews the research progress of the comorbidity of AD with diabetes, obesity and hypercholesterolemia, and summarizes the different roles of animal models in the study of AD to provide references for researchers.
... An alternative wintering strategy, hibernation, involves substantial metabolic changes (19,20) regulated by a genetic toolkit of metabolic pathways, circadian rhythms, and thermogenesis (21). Many of the metabolic changes of wintering strategies are related to the metabolic dysregulation also observed in human neurodegenerative diseases (22)(23)(24)(25). As wintering survival strategies are a continuum of conserved processes (26), brain and metabolic alteration in DP could resemble mechanisms of hibernation. ...
To meet the challenge of wintering in place many high-latitude small mammals reduce energy demands through hibernation. In contrast, short-lived Eurasian common shrews, Sorex araneus, remain active and shrink, including energy-intensive organs in winter, regrowing in spring in an evolved strategy called Dehnel's phenomenon. How this size change is linked to metabolic and regulatory changes to sustain their high metabolism is unknown. We analyzed metabolic, proteomic, and gene expression profiles spanning the entirety of Dehnel's seasonal cycle in wild shrews. We show regulatory changes to oxidative phosphorylation and increased fatty acid metabolism during autumn-to-winter shrinkage, as previously found in hibernating species. But in shrews we also found upregulated winter expression of genes involved in gluconeogenesis: the biosynthesis of glucose from non-carbohydrate substrates. Co-expression models revealed changes in size and metabolic gene expression interconnect via FOXO signaling, whose overexpression reduces size and extends lifespan in many model organisms. We propose that while shifts in gluconeogenesis meet the challenge posed by high metabolic rate and active winter lifestyle, FOXO signaling is central to Dehnel's phenomenon, with spring downregulation limiting lifespan in these shrews.
... Sex differences in Δ 9 -THC-induced antinociception could be attributable to differences in sex hormone signaling, or interactions between sex hormones and the endocannabinoid system. For example, estrogen can interfere with ∆ 9 -THC's ability to bind to CB 1 R (Wakley et al. 2014a) while testosterone may have protective effects on inflammation (Jayaraman et al. 2014;Klein and Flanagan 2016;Roglio et al. 2007). Previous work in rats determined that endocannabinoid levels fluctuate across the estrous cycle in several brain regions (Bradshaw et al. 2006;de Fonseca et al. 1994a;González et al. 2000) and that hormone fluctuations across the estrus cycle can alter the efficacy of G protein coupling to CB 1 R (Riebe et al. 2010) without altering CB 1 R density (Farquhar et al. 2019). ...
Cannabinoids are increasingly used to alleviate pain; however, tolerance to their antinociceptive effects, including those of delta-9-tetrahydrocannabinol (Δ⁹-THC), may limit their therapeutic utility. With more women than men using medical cannabis for pain relief, it is crucial to understand how sex influences cannabinoid-mediated antinociception and tolerance. Though studies in rats consistently find females are more sensitive to the acute antinociceptive effects of cannabinoids, our work with mice consistently finds the converse. The present study examined whether our observed sex differences in Δ⁹-THC-induced antinociception and tolerance are consistent across multiple mouse strains or are strain-dependent. Male and female C57BL/6J (B6), DBA/2, AKR, and CBA/J mice were assessed for differences in acute Δ⁹-THC-induced antinociception and hypothermia prior to and following seven days of once-daily Δ⁹-THC administration. Consistent with our previous findings, male B6 mice were more sensitive to the acute antinociceptive effects of Δ⁹-THC than female littermates, an effect which dissipated with age. B6 males had decreased cannabinoid expression in the PAG compared to females. While DBA and CBA female mice showed increased Δ⁹-THC-antinociception compared to male littermates at 30 and 10 mg/kg Δ⁹-THC, respectively, these differences were less pronounced at higher doses, revealing that dose of Δ⁹-THC may also be important. Overall, CBA mice were more sensitive to Δ⁹-THC-induced antinociception while AKR mice were less responsive. These studies highlight the therapeutic potential of Δ⁹-THC in pain management and underscore the importance of considering not only Δ⁹-THC dose as a function of sex, but potentially genetic differences when evaluating their clinical utility.
... Its impact on neuroinflammation has been extensively studied. HFD feeding induces the activation of the NF-κB (Nuclear Factor kappa B) pathway and the subsequent expression of inflammatory mediators in the hippocampus (Beilharz, et al., 2016;Wang, et al., 2016; in the amygdala (Almeida-Suhett, et al., 2017), as well as increased levels of TNFα (Tumor Necrosis Factor alpha) messenger RNA and IL-1β in the cerebral cortex (Jayaraman, et al., 2014). and found increased levels of IL-6, MCP-1 (Macrophage Chemoattractant Protein-1) and TNFα (Pistell, et al., 2010) and in the brainstem elevated levels of TNFα and IL-1β (Hao, et al., 2016;Speretta, et al., 2016). ...
Obesity is one of the main health problems worldwide. It is a disease that is associated with excessive food consumption, although it is also associated with a process of chronic inflammation and with a group of disorders known as metabolic syndrome. Some of the most distinctive characteristics of obesity are that the individual's adipocytes are hypertrophied, have an irregular adipokine secretion profile, have increased recruitment of inflammatory cells, and altered metabolic homeostasis; which eventually results in the development of various important pathologies or conditions, such as insulin resistance and mitochondrial dysfunction. This review aims to present the current knowledge on inflammation of adipose tissue associated with obesity.
... In recent years, inflammation responses with Celsus' four cardinal signs, namely heat, pain, redness and swelling have attracted increasing attention [1]. Inflammation responses play an important role in multiple diseases with a high prevalence among population, such as hepatitis [2], lung disease [3] and Alzheimer's disease [4]. And, they are also centrally related to the pathogenesis of a large number of acute and chronic diseases, such as rheumatoid arthritis [5], colonic inflammatory response [6], dermatitis [7]. ...
