To evaluate associations of birth weight, midlife weight, and their transitions with mild cognitive impairment (MCI) and brain MRI indices.

This prospective cohort study included 200,726 UK Biobank participants. Self-reported birth weight and measured midlife anthropometrics were used to classify obesity (waist circumference [WC]/waist-to-hip ratio [WHR]). We constructed nine weight transition patterns from birth to midlife WC, six from birth to midlife WHR. Cox proportional hazards models and linear regression models were used to examine associations of birth weight, midlife body size and their transitions with MCI and brain MRI indices.

Compared to normal birth weight, low birth weight (HR: 1.29, 95 % CI: 1.16-1.44) and high birth weight (1.11, 1.01-1.22) were both associated with increased risk of MCI, showing a U-shaped relationship. Compared to normal weight at midlife, midlife central obesity [WC (1.25, 1.15-1.37) and WHR (1.27, 1.17-1.37)] were significantly associated with elevated MCI risk. Compared to individuals with normal weight at birth and midlife, those with low birth weight who transition to central obesity at midlife, defined by WC (1.51, 1.27-1.78) or WHR (1.42, 1.22-1.66), showed the highest risk of MCI. Weight transitions were also associated with brain structure, individuals who had low or high birth weight and developed midlife obesity showed significant reductions in total brain volume and grey matter volume, as well as increases in white matter hyperintensity volume.

Birth weight exhibited a U-shaped association with MCI risk. Individuals transitioning from low birth weight to midlife central obesity demonstrated the highest MCI susceptibility.

Alzheimer's disease (AD) represents a leading cause of dementia, characterized by progressive cognitive and functional decline. Although extensive research has unraveled critical aspects of AD pathology, its etiology remains incompletely understood, urging further exploration into potential risk factors. Growing evidence underscores a significant link between cardiovascular disease (CVD) risk factors and AD, with modifiable lifestyle elements - such as physical inactivity, high low-density lipoprotein (LDL) levels, obesity, hypertension, atherosclerosis, and diabetes - emerging as contributors to cerebrovascular damage and neurodegeneration. ADAM10, a disintegrin and metalloproteinase involved in the non-amyloidogenic processing of amyloid precursor protein (APP), has garnered interest for its dual role in cardiovascular and neurodegenerative processes. ADAM10's regulation of neuroinflammation, endothelial function, and proteolytic cleavage of APP potentially moderates amyloid-β (Aβ) peptide formation, thus influencing both cardiovascular and brain health. Given these interconnected roles, this narrative review investigates whether ADAM10-driven vascular dysfunction accelerates neurodegeneration, how lipid metabolism influences ADAM10 activity in CVD and AD, and whether targeting ADAM10 could offer a dual-benefit therapeutic strategy to mitigate disease burden. By exploring epidemiological data, clinical studies, and molecular pathways, we aim to clarify ADAM10's bridging function between AD and cardiovascular risk, offering a new perspective into therapeutic opportunities to alleviate the dual burden of these interrelated conditions.

The human brain acts as a crucial organ that requires a high glucose metabolic content. However, abnormal glucose levels act as a major factor for frequent epileptic foci. Thus, it has come to attention in the recent past that epilepsy is a metabolic problem in addition to a neurological condition. However, several studies have postulated a link between epilepsy and diabetes mellitus, but very few have emphasized the exact molecular mechanism behind it and its related specific targets. Hence, this article mainly outlines in-depth knowledge about the molecular mechanisms involved and its associated target approaches. Data from several publications, such as meta-analysis, systematic and narrative reviews, and research papers obtained from electronic databases, have been used for postulating a strong evidence in order to establish a comprehensive article addressing this problem in depth. The data discussed here have revealed how adiponectin levels and mitochondrial activity impact obesity, type 2 diabetes mellitus (T2DM), and epilepsy. We have also tried to give a brief idea about the possible theories that would also impact the severity of these two conditions, including adequate exercise and the impact of commonly used AEDs. Furthermore, one of the factors causing genetic predisposition to seizures due to glucose metabolism, such as GLUT-1 deficiency, has also been described briefly. It has to be mentioned that researchers and clinical practitioners might need to take these factors into account while discovering and evaluating a suitable novel therapeutic in the future.

BackgroundDisordered metabolism affects risk for cognitive decline, Alzheimer's disease, and other dementias, likely through pathways involving adipokines.ObjectiveAnalyze incident cognitive impairment in relation to leptin, adiponectin, body mass index, and other risk factors.MethodsNested case-control study within the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort of 30,239 adults in the US. Cases with incident cognitive impairment (n = 489) scored >1.57 SD below demographically adjusted means on ≥2 of 3 cognitive tests: word list learning, word list delayed recall, and category fluency. Cognitively intact controls (n = 583) were randomly selected within demographic strata. Leptin and adiponectin were assayed in thawed blood that had been stored at baseline.ResultsIn participants with normal weight, lower leptin was associated with higher odds of cognitive impairment. Relative to leptin = 25 ng/mL, adjusted ORs were 1.5 (95% CI: 1.2, 1.9) at leptin = 15 ng/mL, 0.8 (0.8, 0.9) at leptin = 30 ng/mL, and 0.5 (0.4, 0.8) at leptin = 45 ng/mL. In participants with obesity, higher adiponectin was associated with higher odds of cognitive impairment. Relative to adiponectin = 25 ng/mL, adjusted ORs were 0.8 (95% CI: 0.7, 1.0) at adiponectin = 15 ng/mL, 1.1 (1.0, 1.2) at adiponectin = 30 ng/mL, and 1.3 (1.0, 1.7) at adiponectin = 45 ng/mL. Associations of adipokines with cognitive impairment varied across levels of other risk factors.ConclusionsAdipokines, in concert with body mass index, play complex roles in cognitive health, with many avenues open for further investigation.

Various forms of neuronal death contribute to neurological injury after traumatic brain injury (TBI), leading to irreversible neurological deficits. Among these, ferroptosis is a form of regulated cell death characterized by the accumulation of iron-dependent lipid hydroperoxides and induced by the incorporation of polyunsaturated fatty acids (PUFAs) into cellular membranes. Adiponectin (APN), a cytokine secreted by adipocytes, have showed neuroprotective effects by binding to adiponectin receptors (AdipoRs), which are widely expressed in the central nervous system. However, the role of APN-AdipoRs signaling in ferroptosis after TBI remains unexplored. Our clinical analysis revealed a significant correlation between serum levels of APN and 6-month outcomes of TBI patients. Subsequent studies confirmed that TBI-induced ferroptosis was more pronounced in APN knockout mice compared to wild-type mice, while additional APN receptor agonist (AdipoRon) treatment significantly mitigated TBI induced ferroptosis. Furthermore, AdipoR1 knockdown significantly diminished the protective effects of AdipoRon against erastin-induced ferroptosis in primary neurons. Correspondingly, in the neuron-specific AdipoR1 conditional knockout (AdipoR1CKO) mice, neurons were more susceptible to ferroptosis after TBI, leading to increased brain edema and lesion volume, and exacerbated neurological deficits. Mechanically, activation of APN-AdipoR1 signaling promoted adenosine monophosphate activated protein kinase (AMPK) -mediated phosphorylation of acetyl-CoA carboxylase-1 (ACC1), thus suppressed the PUFAs biosynthesis, which determines theferroptosissensitivity of neurons. Taken together, these findings provided compelling evidence for the protective role of APN-AdipoR1 signaling against TBI-induced ferroptosis by inhibiting AMPK-ACC1.

Perioperative neurocognitive disorder (PND) is a significant complication affecting elderly patients after surgery, with limited effective interventions to improve its prognosis yet. We have found that decreased serum adiponectin (APN) and increased cerebrospinal fluid (CSF) lactate are involved in the pathophysiological process of PND in elderly patients. APN is known for its anti-insulin resistance property. In this study, we further explored the regulatory effects of APN on cerebral glucose metabolism in PND rats. Twelve-month-old male Sprague-Dawley rats were divided into 3 groups: the sham, PND (splenectomy) and PND+APN (50 mg/kg/day intragastrically) groups. ELISA, quantitative PCR and colorimetric analysis were conducted to analyze tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), pyruvate and lactate in serum, CSF and hippocampus. Open field and Morris water maze (MWM) tests were used to detect hippocampus-dependent cognitive function. Western blot and flow cytometry were conducted to detect neuronal apoptosis in primary hippocampal neurons. In vivo, peripheral APN administration reversed surgery-induced reductions in serum APN expression and elevated levels of cerebral lactate, the ratio of lactate/pyruvate, TNF-α and IL-1β, thereby improving cognitive performance in MWM and Open Field tests. In vitro, APN at concentrations of 2 and 10 ng/ml dose-dependently reduced lipopolysaccharide-induced caspase 3 expression and p38 phosphorylation in neurons, inhibiting apoptosis. Cerebral hypometabolism is one of the pathogenic mechanisms of PND. APN shows its effects on regulating glucose metabolism to inhibit neuroinflammation and neuronal apoptosis in PND. And the underlying mechanism of APN should be investigated further.

Background/Objectives: Previous studies have shown that adiponectin deficiency or blocking adiponectin receptors (AdipoRs) in the brain can lead to an Alzheimer's disease (AD)-like neuropathology. While AdipoRs are abundantly expressed in peripheral tissues, the effects of blocking these receptors in the peripheral tissues on the brain are unclear. This study investigates the impacts of blocking AdipoRs with a peripheral administration of ADP400, an antagonist peptide that targets AdipoRs on cognitive performance, hippocampal adult neurogenesis, and AD-like neuropathology in mice. Methods: Adult mice were intraperitoneally administered with ADP400 peptide that blocks peripheral AdipoRs continuously for 21 days, followed by a battery of behavioral test for mood and memory performance. Results: ADP400-treated mice exhibited impaired memory performance and increased anxiety-like behaviors. Molecular analyses revealed heightened hyperphosphorylation of tau and increased β-amyloid levels, alongside decreased expression of AdipoRs and PP2A in the hippocampus, suggesting a critical role of AdipoRs in AD-like neuropathology. Furthermore, ADP400 treatment significantly reduced hippocampal adult neurogenesis, as indicated by decreased BrdU, Ki67, and DCX staining. Inhibiting peripheral adiponectin receptors could lead to tau hyperphosphorylation and accumulated β-amyloid levels. Conclusions: These findings highlight the critical role of peripheral manipulation of adiponectin receptors in modulating cognitive function and adult neurogenesis, offering insights into potential therapeutic strategies for AD and related cognitive disorders.

Postoperative neurocognitive dysfunction (PND) represents a form of cognitive impairment related to surgery and anesthesia, which may manifest hours or even weeks after the surgical procedure, persist, and potentially progress into Alzheimer's disease. The etiology of PND is intricate, with central nervous inflammation playing a crucial role. The clinical manifestations of PND are not distinctive, no obvious image alterations are observable, and the diagnosis rate is relatively low, thereby influencing prognosis and augmenting postoperative complications and mortality. The optimal treatment approach for PND lies in timely identification and management of the high-risk factors causing PND and implementing early prevention. We hypothesize that the level of peripheral blood adiponectin (APN) is correlated with PND, potentially through inhibiting the central inflammatory response and regulating brain energy metabolism.

Fifty elderly patients undergoing elective hip arthroplasty under continuous epidural spinal anesthesia (CESA) were included. Cognitive function was assessed using the Mini-Mental State Examination (MMSE) preoperatively and postoperatively at 1, 2, 3, and 7 days. Serum APN and CSF levels of TNF-α, IL-1β, lactic acid, and pyruvic acid were measured. The occurrence of PND was recorded, and the patients were divided into a PND group and a non-PND group.

PND occurred in 16 patients (34.04%). The PND group had lower serum APN levels and higher cerebrospinal fluid (CSF) concentrations of TNF-α, IL-1β, and lactic acid compared to the non-PND group. CSF TNF-α and IL-1β levels were negatively correlated with serum APN concentration. These biomarkers are associated with PND occurrence and have high diagnostic value.

Decreases in serum APN and increases in TNF-α, IL-1β, and lactic acid in CSF may be involved in the pathophysiological process of PND in elderly patients after surgery.

Platinum-based chemotherapy provides curative treatment to more than 95% of patients with testicular germ cell tumor but it has negative cardiometabolic and neurological effects. Regular exercise can alleviate late chemotherapy-related toxicities. We examined the impact of a 6-month supervised aerobic-strength training on cognitive and cardiometabolic health and residual level of platinum in cancer survivors.

Twenty-eight middle-aged (42.1 ± 7.6 years) testicular germ cell tumor survivors subjected to platinum-based chemotherapy (1-8 cycles, 0-24 years ago) were recruited into exercise (n = 20) and control (n = 8) groups. Effects of 6-month exercise training on the whole-body and muscle metabolism, cognitive functions, cardiopulmonary fitness, residual plasma platinum, and plasma adiponectin were examined.

Exercise intervention improved cardiopulmonary fitness and cognitive functions, reduced residual plasma platinum, visceral adiposity and muscle lipids, improved glucose (glycosylated hemoglobin) and lipid (high-density lipoprotein cholesterol) metabolism, and enhanced dynamics of muscle post-exercise phosphocreatine recovery. Exercise-related decline in plasma platinum was paralleled by decline of muscle glycerophosphocholines and by the enhanced metabolic flexibility during low-intensity exercise, and predicted training-induced increase in cognitive functions.

The 6-month exercise intervention resulted in improved cognitive and cardiometabolic health in testicular germ cell tumor survivors, which was paralleled by reduced plasma platinum, providing evidence that structured supervised exercise brings multiple health benefits to testicular germ cell tumor survivors.

The worldwide health system faces challenges from obesity and related metabolic disorders because they exhibit both rising rates of occurrence and intricate pathophysiological mechanisms. This work examines how adipokines interact with body composition during obesity to control important metabolic functions. Bioactive molecules produced by adipose tissue function as adipokines which regulate essential biological pathways that control inflammation response and insulin sensitivity alongside energy balance management and immune system operation. The disruption of adipokine secretion and function leads directly to metabolic disorders which include insulin resistance and persistent inflammation characteristic of obesity-related conditions. This article investigates the therapeutic possibilities of adipokine pathway manipulation through new pharmacological approaches and lifestyle changes alongside personalized medicine developments. Researchers analyze adipokines as important biomarkers for patient disease classification and their application in creating individualized treatment plans. The review highlights existing research deficiencies and obstacles that stand in the way of applying adipokine discoveries to clinical settings. This article integrates existing research to show how adipokine regulation helps prevent obesity-related metabolic issues and suggests directions for future studies to enhance treatment results.

A high-fat diet and physical inactivity are key contributors to obesity, predisposing individuals to various chronic diseases, such as cardiovascular disease and diabetes, which involve multiple organs and tissues. To better understand the role of multi-organ interaction mechanisms in the rising incidence of obesity and its associated chronic conditions, treatment and prevention strategies are being extensively investigated. This review examines the signaling mechanisms between different tissues and organs, with a particular focus on the crosstalk between adipose tissue and the muscle, brain, liver, and heart, and potentially offers new strategies for the treatment and management of obesity and its complications.

Although many efforts have been made to understand the pathophysiological mechanisms of COVID-19, critical gaps remain to be explored. This study aimed to investigate potential alterations in adipokine levels (specifically adiponectin, leptin, and resistin) among individuals with COVID-19. Within this population, we further assessed the association between these markers with both, body mass index (BMI) and psychiatric symptoms. This cross-sectional study included an age- and sex-matched sample of adults with COVID-19 (cases) and without COVID-19 (controls). We evaluated the severity of psychiatric symptoms, BMI, and adipokines. Individuals with COVID-19 presented greater BMI, stress levels, and leptin levels when compared to controls. Leptin levels were greater in individuals with moderate/severe COVID-19 as compared to individuals with COVID-19 who were asymptomatic or having mild symptoms. Leptin levels were positively correlated with BMI, severity of depressive and anxiety symptoms, and stress levels in the total sample. Leptin levels were also positively correlated with BMI, severity of anxiety symptoms, and stress levels in controls. In cases, there was a positive correlation between adiponectin and the severity of depressive symptoms and stress levels and leptin/resistin with BMI. A linear regression model revealed that BMI, severity of anxiety symptoms, and the diagnosis of COVID-19 are independently associated with increased leptin levels. Thus, leptin levels seem to be impacted by the COVID-19 infection, anxiety, and BMI.

Sepsis is a life-threatening syndrome characterized by organ dysfunction, resulting from an uncontrolled or abnormal immune response to infection, which leads to septicemia. It involves a disruption of immune homeostasis, marked by the release of Inflammatory factors and dysfunction of immune cells. Adiponectin is widely recognized as an anti-inflammatory mediator, playing a crucial role in regulating immune cell function and exerting protective effects on tissues and organs. However, the physiological role of adiponectin in septicemia remains unclear due to the condition's association with immune response dysregulation and organ damage. This study focuses on the potential relationship between adiponectin and excessive immune responses, along with organ injury in septicemia. Additionally, we investigate possible explanations for the observed discrepancies in adiponectin levels among critically ill or deceased patients compared to theoretical expectations, aiming to provide valuable insights for clinical diagnostics and therapeutic interventions in sepsis.

Profiling circulating lipids and metabolites in Parkinson's disease (PD) patients could be useful not only to highlight new pathways affected in PD condition but also to identify sensitive and effective biomarkers for early disease detection and potentially effective therapeutic interventions. In this study we adopted an untargeted omics approach in three groups of patients (No L-Dopa, L-Dopa and DBS) to disclose whether long-term levodopa treatment with or without deep brain stimulation (DBS) could reflect a characteristic lipidomic and metabolomic signature at circulating level. Our findings disclosed a wide up regulation of the majority of differentially regulated lipid species that increase with disease progression and severity. We found a relevant modulation of triacylglycerols and acyl-carnitines, together with an altered profile in adiponectin and leptin, that can differentiate the DBS treated group from the others PD patients. We found a highly significant increase of exosyl ceramides (Hex2Cer) and sphingoid bases (SPB) in PD patients mainly in DBS group (p < 0.0001), which also resulted in a highly accurate diagnostic performance. At metabolomic level, we found a wide dysregulation of pathways involved in the biosynthesis and metabolism of several amino acids. The most interesting finding was the identification of a specific modulation of L-glutamic acid in the three groups of patients. L-glutamate levels increased slightly in No L-Dopa and highly in L-Dopa patients while decreased in DBS, suggesting that DBS therapy might have a beneficial effect on the glutamatergic cascade. All together, these data provide novel insights into the molecular and metabolic alterations underlying PD therapy and might be relevant for PD prediction, diagnosis and treatment.

Green tea polyphenols (GTP) have been shown to ameliorate lipid metabolic disorders by regulating intestinal bacteria. Given the significant role of intestinal bacteriophages in shaping the gut microbiota, this study investigates GTP's influence on gut bacteriophage-bacteria interactions and lipid metabolism using metagenomics and metabonomics. The research results indicated that GTP significantly reduced body weight, serum triglycerides, leptin, insulin resistance, interleukin-6, and TNF-α levels while increasing adiponectin in ob/ob mice fed high-fat diet, aiding intestinal repair. GTP improved gut health by decreasing Enterobacter, Siphoviridae and Enterobacteria_phage_sfv, increasing Bifidobacterium and intestinal metabolites SCFA and hippuric acid. Correlation analysis showed negative correlations between Enterobacter sp. 50,588,862 and Enterobacteria_phages, Shigella_phages with 4-hydroxyphenylpyruvate and hippuric acid. Bifidobacterium choerinum and Bifidobacterium sp. AGR2158 were positively correlated with fatty acids and bile acids. In conclusion, GTP reduced fat accumulation and inflammation, enhanced gut barrier function in obese mice, closely associated with changes in the gut bacteriophage community.

Obesity-induced insulin resistance (IR) can precipitate metabolic disorders such as diabetes. Zeaxanthin, a crucial member of the carotenoid family, has been found to mitigate the damage caused by obesity. However, reports on the effects of zeaxanthin on obesity-induced IR are lacking. Our objective was to examine the metabolic regulatory impacts of zeaxanthin on mice subjected to a high-fat diet (HFD) that triggered IR and to explore their influence on gut microbiota regulation. This study constructed a mouse model of metabolic dysfunction caused by lipid-rich nutritional patterns to investigate physiological and biochemical indices, liver pathway expression, and the intestinal microbiota. The mechanisms by which zeaxanthin improved both IR and glucose metabolic disorders were elucidated. The results demonstrate that zeaxanthin effectively suppressed obesity. The fasting blood glucose, area under curve of oral glucose tolerance test and insulin tolerance test, and homeostatic model assessment-insulin resistance (HOMA-IR) indices in the HFDZEA group decreased by 14.9%, 25.2%, 28.9%, and 29.8%. Additionally, zeaxanthin improved the lipid metabolism and alleviated damage to the liver and pancreas while also activating the PI3K/Akt pathway, regulating hepatic gluconeogenesis and the glycogen metabolism. The number of OTUs in the HFDZEA group increased by 29.04%. Zeaxanthin improved the structure and profile of the gastrointestinal microbiome and enhanced its diversity, increasing probiotics abundance, decreasing pathogen abundance, and thereby ameliorating the dysbiosis of enteric microbial communities in rodents with obesity resulting from excessive fat consumption. The outcomes of our analysis provide a rational basis for advancing zeaxanthin-based nutritional products.

Some studies suggest that low-grade inflammation and adipokines may be involved in mild cognitive impairment (MCI) and depression in subjects with type 2 diabetes; however, the available data concerning the elderly population are limited. Therefore, we conducted novel research to determine the serum adiponectin, hs-CRP and TNF-α levels in elderly diabetic patients with MCI and depressive symptoms and to identify the factors associated with MCI in this group. A total of 178 diabetic patients (mean age 84.4 ± 3.4 years) were screened for MCI and depressive symptoms. Various biochemical and biomarker data were collected. We found that patients with MCI and depressive symptoms demonstrated lower adiponectin levels and high hs-CRP and TNF-α. In this group, adiponectin concentration was negatively correlated with hs-CRP, TNF-α, HbA1c, and GDS-30 scores and positively correlated with MoCA scores. Multivariable analysis found the risk of MCI to be associated with higher TNF-α levels, fewer years of formal education, an increased number of comorbidities, and the presence of CVD. We concluded that low-grade inflammation and the presence of adipokines are associated with MCI and depressive symptoms in elderly diabetics. Further research should evaluate the suitability of Hs-CRP, TNF-α, and adiponectin as diagnostic markers for MCI and potential therapeutic targets.

Solid organ transplantation is a life-saving treatment for patients with end-stage organ failure, but it poses unique challenges due to metabolic and immunological changes in recipients. One significant complication is post-transplant diabetes mellitus (PTDM), which affects a variety of solid organ recipients. Leptin, a hormone produced by adipose tissue, regulates appetite and affects glucose metabolism. High leptin levels are associated with the development of PTDM, especially in kidney transplant recipients. Adiponectin, another adipokine, increases insulin sensitivity and has anti-diabetic properties. Low adiponectin levels are associated with insulin resistance and increase the risk of PTDM. As the incidence of PTDM increases due to the increased life expectancy among transplant patients, understanding the role of adipokines such as leptin and adiponectin becomes crucial for early detection and treatment. Additional studies on other adipokines may also provide valuable information on the pathogenesis of PTDM.

Type 2 diabetes mellitus (T2DM) is associated with decreased heart rate variability (HRV) with an unclear intermediate mechanism. This study aimed to conduct mediation analysis to explore the impact of various adipose tissues on the relationship between T2DM and HRV.

A total of 380 participants were enrolled for analysis, including 249 patients with T2DM and 131 non-diabetic controls. The thicknesses of four adipose tissues (subcutaneous, extraperitoneal, intraperitoneal, and epicardial) were measured by abdominal ultrasound or echocardiography respectively. HRV was assessed by 24-hour Holter for monitoring both frequency domain indices (LF, HF, and LF/HF) and time domain indices (SDNN, SDANN, SDNN index, rMSSD and pNN50). Mediation analysis was used toexamine whether adipose tissues mediated the relationship between T2DM and each index of HRV. Then, a latent variable - HRV burden - was constructed by structural equation model with selected HRV indices to comprehensively assess the whole HRV.

Compared to non-diabetic controls, patients with T2DM exhibited a significant reduction in indices of HRV, and a remarkable increase in the thicknesses of extraperitoneal, intraperitoneal, and epicardial adipose tissues. Mediation analysis found significant indirect effects of T2DM on six indices of HRV, including HF, SDNN, SDANN, SDNN index, rMSSD, and pNN50, which was mediated by epicardial adipose tissue rather than other adipose tissues, with the mediation proportions of 64.21%, 16.38%, 68.33%, 24.34%, 24.10% and 30.51%, respectively. Additionally, epicardial adipose tissue partially mediated the relationship between T2DM and reduced HRV burden (24.26%), which composed by SDNN, SDNN index, rMSSD, and pNN50.

Epicardial adipose tissue partially mediated the relationship between T2DM and reduced HRV, which reinforces the value of targeting heart-specific visceral fat to prevent cardiac autonomic neuropathy in diabetes.

In dairy cows, the occurrence of subclinical ketosis (SCK) is particularly high during early lactation. Previously, we documented alterations in the abundance of adiponectin (ADPN) in anestrus cows with SCK in comparison to cows in estrus. In the present study, 60 cows were divided into two groups: control (C, n = 30) and SCK (n = 30). Based on cow's estrus situation in two group at 55-60 days postpartum, 15 anestrus SCK cows and estrus cows were designated the SCK-A group and C-E group, respectively. The SCK-A group had downregulated serum and follicular fluid ADPN levels compared with the C-E group. The serum ADPN level was positively correlated with the insulin level and follicle growth rate, and there was a positive correlation between ADPN and glucose in the follicular fluid. Primary culture of dairy cow granulosa cells (GCs) was established to observe the effect of low glucose (Glu) and/or ADPN on GCs cyclins and proteins important for steroid synthesis. The results showed that the addition of 1 µg/mL ADPN alleviated the negative effects of low Glu treatment on the proliferation of GCs and the expression of steroid secretion related protein proteins. Treatment with LY294002 (PI3K inhibitor) four experimental GCs groups: control (0 µg/mL ADPN), 1 µg/mL ADPN, LY294002 inhibitor, and 1 µg/mL ADPN+LY294002. The results showed that ADPN promotes the secretion of steroid hormones by GCs through the PI3K-AKT. In summary, ADPN plays a crucial role in ameliorating postpartum anestrus in dairy cows with SCK.

Alzheimer's disease (AD) is a leading cause of cognitive impairment worldwide. Overweight and obesity are strongly associated with comorbidities, such as hypertension, diabetes, and insulin resistance (IR), which contribute substantially to the development of AD and subsequent morbidity and mortality. Adipose tissue (AT) is a highly dynamic organ composed of a diverse array of cell types, which can be classified based on their anatomic localization or cellular composition. The expansion and remodeling of AT in the context of obesity involves immunometabolic and functional shifts steered by the intertwined actions of multiple immune cells and cytokine signaling within AT, which contribute to the development of metabolic disorders, IR, and systemic markers of chronic low-grade inflammation. Chronic low-grade inflammation, a prolonged, low-dose stimulation by specific immunogens that can progress from localized sites and affect multiple organs throughout the body, leads to neurodystrophy, increased apoptosis, and disruption of homeostasis, manifesting as brain atrophy and AD-related pathology. In this review, we sought to elucidate the mechanisms by which AT contributes to the onset and progression of AD in obesity through the mediation of chronic low-grade inflammation, particularly focusing on the roles of adipokines and AT-resident immune cells.

There is growing evidence showing that adiponectin (APN) can improve Alzheimer's disease(AD)-like pathological changes by improving insulin resistance. However, the role of AdipoRon (an Adiponectin receptor agonist) on synaptic plasticity and cognitive dysfunction in the early stages of type 2 diabetes mellitus(T2DM) remains unknown. In this study, we investigated the neuroprotective effect and the molecular mechanism underlying the effect of AdipoRon in T2DM mice. We found that AdipoRon significantly restored the cognitive deficits in T2DM mice, including shorter escape latency, more crossing times, increased distances, and percentage of time in the target quadrant. In addition, AdipoRon treatment up-regulated synaptic proteins (PSD95, SYN, GAP43, and SYP), increased the number of hippocampal synapses and attenuated synaptic damage, including the length, the number and the density of dendritic spines in CA1 and DG regions. Furthermore, AdipoRon attenuated Tau phosphorylation at multiple AD-related sites (p-tau 205, p-tau 396, p-tau 404) by promoting AdipoR expression and activating the AMPK/mTOR pathway. Our data suggests that AdipoRon exerts neuroprotective effects on the T2DM mice, which may be mediated by the activation of the AdipoR/AMPK/mTOR signaling pathway.

Curcumin (Curcumin) belongs to the polyphenol family. It is extracted by drying the root of a plant of Asian origin, belonging to the Zingiberaceae family. The best-known species is Curcumincuma Longa. Curcumin has been recognized as having great therapeutic powers since ancient times. Studies on curcumin have since confirmed its powerful antioxidant properties, preventing both the formation of free radicals and their neutralization, having anti-inflammatory, antibacterial, immunological, and neuroprotective properties, as well as being a regulator of the intestinal microbiota with beneficial effects on the clinical manifestations of metabolic syndrome. Our study aimed to highlight how all these therapeutic aspects could benefit oral health, both preventing and improving the course of pathological processes. The effect of mouthwashes, and curcumin-based gels on the regulation of bacterial plaque and in the control of gingivitis, was largely comparable to that of using 0.20% chlorhexidine, with fewer side effects. Being a highly hydrophobic substance, it has a high permeability to cross the cell membrane. Bioavailability increases when combined with liposoluble substances (e.g., olive oil) and piperine, which improves absorption. Curcumin also has a negligible degree of toxicity, making it an excellent alternative to the use of gold standard products for oral disinfection.

Adiponectin is a pleiotropic cytokine predominantly derived from adipose tissue. In addition to its role in regulating energy metabolism, adiponectin may also be related to estrogen-dependent diseases, and many studies have confirmed its involvement in mediating diverse biological processes, including apoptosis, autophagy, inflammation, angiogenesis, and fibrosis, all of which are related to the pathogenesis of endometriosis. Although many researchers have reported low levels of adiponectin in patients with endometriosis and suggested that it may serve as a protective factor against the development of the disease. Therefore, the purpose of this review was to provide an up-to-date summary of the roles of adiponectin and its downstream cytokines and signaling pathways in the aforementioned biological processes. Further systematic studies on the molecular and cellular mechanisms of action of adiponectin may provide novel insights into the pathophysiology of endometriosis as well as potential therapeutic targets.

Neurodegenerative diseases (NDDs) such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis epitomize a class of insidious and relentless neurological conditions that are difficult to cure. Conventional therapeutic regimens often fail due to the late onset of symptoms, which occurs well after irreversible neurodegeneration has begun. The integrity of the blood-brain barrier (BBB) further impedes efficacious drug delivery to the central nervous system, presenting a formidable challenge in the pharmacological treatment of NDDs. Recent scientific inquiries have shifted focus toward the peripheral biological systems, investigating their influence on central neuropathology through the lens of extracellular vesicles (EVs). These vesicles, distinguished by their ability to breach the BBB, are emerging as dual operatives in the context of NDDs, both as conveyors of pathogenic entities and as prospective vectors for therapeutic agents. This review critically summarizes the burgeoning evidence on the role of extracerebral EVs, particularly those originating from bone, adipose tissue, and gut microbiota, in modulating brain pathophysiology. It underscores the duplicity potential of peripheral EVs as modulators of disease progression and suggests their potential as novel vehicles for targeted therapeutic delivery, positing a transformative impact on the future landscape of NDD treatment strategies. Search strategy A comprehensive literature search was conducted using PubMed, Web of Science, and Scopus from January 2000 to December 2023. The search combined the following terms using Boolean operators: "neurodegenerative disease" OR "Alzheimer's disease" OR "Parkinson's disease" OR "Amyotrophic lateral sclerosis" AND "extracellular vesicles" OR "exosomes" OR "outer membrane vesicles" AND "drug delivery systems" AND "blood-brain barrier". MeSH terms were employed when searching PubMed to refine the results. Studies were included if they were published in English, involved human subjects, and focused on the peripheral origins of EVs, specifically from bone, adipose tissue, and gut microbiota, and their association with related diseases such as osteoporosis, metabolic syndrome, and gut dysbiosis. Articles were excluded if they did not address the role of EVs in the context of NDDs or did not discuss therapeutic applications. The titles and abstracts of retrieved articles were screened using a dual-review process to ensure relevance and accuracy. The reference lists of selected articles were also examined to identify additional relevant studies.

The adipokines secreted by adipocytes might play an important role through crossing the blood brain barrier to the brain, which could mediate the common physiological pathway between depression and obesity. CTRP4, a member of the CTRP family, is highly expressed in human adipose tissue and brain tissue.

this study aimed to measure serum C1q/TNF-related protein 4 (CTRP4) levels in depressive patients to explore the association between CTRP4 levels and depression.

depressive patients (n = 138), healthy controls (n = 100) were enrolled from September 2020 to December 2021. The level of serum CTRP4 was measured by enzymes linked to immunosorbent assay (ELISA). Other biochemical indicators were measured by Advia 2400 automatic biochemistry analyzer. Depressive symptoms of patients were assessed using the Hamilton Depression Scale-24 item (HAMD-24).

this study found that serum CTRP4 levels in the MDD group were lower than that of the health control (P < 0.001). Serum CTRP4 levels were negatively correlated with HAMD-24 scores (r = -0.368; P = 0.001). The serum CTRP4 levels were negatively correlated with Total Cholesterol (TC), Triglyceride (TG) and Low-Density Lipoprotein Cholesterol (LDL-C), but were positively associated with high density lipid-cholesterol (HDL-C) (r = -0.267, r = -0.255, r = -0.312 and r = 0.280; P = 0.017, P = 0.023, P = 0.005 and P = 0.012). The ROC curve of CTRP4 showed that the Area Under Curve (AUC) was 0.856, P < 0.001.

the serum CTRP4 levels in MDD patients were lower than that in health control, which might mediate the physiological progress of MDD patients.

For much of human evolution, the average lifespan was <40 years, due in part to disease, infant mortality, predators, food insecurity, and, for females, complications of childbirth. Thus, for much of evolution, many females did not reach the age of menopause (45-50 years of age) and it is mainly in the past several hundred years that the lifespan has been extended to >75 years, primarily due to public health advances, medical interventions, antibiotics, and nutrition. Therefore, the underlying biological mechanisms responsible for disease risk following menopause must have evolved during the complex processes leading to Homo sapiens to serve functions in the pre-menopausal state. Furthermore, as a primary function for the survival of the species is effective reproduction, it is likely that most of the advantages of having such post-menopausal risks relate to reproduction and the ability to address environmental stresses. This opinion/perspective will be discussed in the context of how such post-menopausal risks could enhance reproduction, with improved survival of offspring, and perhaps why such risks are preserved. Not all post-menopausal females exhibit risk for this set of diseases, and those who do develop such diseases do not have all of the conditions. The diseases of the post-menopausal state do not operate as a unified complex, but as independent variables, with the potential for some overlap. The how and why there would be such heterogeneity if the risk factors serve essential functions during the reproductive years is also discussed and the concept of sets of reversible epigenetic changes associated with puberty, pregnancy, and lactation is offered to explain the observations regarding the distribution of post-menopausal conditions and their potential roles in reproduction. While the involvement of an epigenetic system with a dynamic "modification-demodification-remodification" paradigm contributing to disease risk is a hypothesis at this point, validation of it could lead to a better understanding of post-menopausal disease risk in the context of reproduction with commonalities may also lead to future improved interventions to control such risk after menopause.

Nonalcoholic fatty liver disease (NAFLD) exponentially affects the global healthcare burden, and it is currently gaining increasing interest in relation to its potential impact on central nervous system (CNS) diseases, especially concerning cognitive deterioration and dementias. Overall, scientific research nowadays extends to different levels, exploring NAFLD's putative proinflammatory mechanism of such dysmetabolic conditions, spreading out from the liver to a multisystemic involvement. The aim of this review is to analyze the most recent scientific literature on cognitive involvement in NAFLD, as well as understand its underlying potential background processes, i.e., neuroinflammation, the role of microbiota in the brain-liver-gut axis, hyperammonemia neurotoxicity, insulin resistance, free fatty acids, and vitamins.

Postmenopausal women with obesity are markedly at risk of cognitive impairment and several health issues. Emerging evidence demonstrated that both diet and exercise, particularly physical-cognitive exercise are involved in cognitive and health benefits. However, the comparative effect of diet, exercise, and combined interventions in postmenopausal women with obesity on cognition and cardiometabolic health is still lacking. Identifying the effective health promotion program and understanding changes in cardiometabolic health linking these interventions to cognition would have important medical implications. This RCT aimed to examine the effect of single and combined interventions of diet and exercise on cognitive function and cardiometabolic health in postmenopausal women with obesity.

Ninety-two postmenopausal women with obesity were randomly assigned to diet group (intermittent fasting 2 days/week, 3 months), exercise group (physical-cognitive exercise 3 days/week, 3 months), combined group, or control group (n = 23/group). All cognitive outcomes and cardiometabolic outcomes were measured at baseline and post-3 months. Primary outcomes were executive functions, memory, and plasma BDNF levels. Secondary outcomes were global cognition, attention, language domain, plasma adiponectin levels, IL-6 levels, metabolic parameters, and physical function.

At the end of the 3-month intervention, the exercise and combined group demonstrated significant memory improvement which was accompanied by significant improvements in plasma BDNF level, insulin levels, HOMA-IR, %body fat, and muscle strength when compared to controls (p < 0.05). Only the combined intervention group demonstrated a significant improvement in executive function and increased plasma adiponectin levels when compared to control (p < 0.05). Surprisingly, no cognitive improvement was observed in the diet group (p > 0.05). Significant reduction in cholesterol levels was shown in the diet and combined groups when compared to controls (p < 0.05). Among the three intervention groups, there were no significant differences in all cognitive outcomes and cardiometabolic outcomes (p > 0.05). However, all three intervention groups showed significant improvements in plasma BDNF levels, weight, BMI, WHR, fat mass, and predicted VO2 max, when compared to control (p < 0.05).

These findings suggest that combined physical-cognitive exercise and dietary intervention are promising interventions to improve cognition and obesity-related complications of postmenopausal women with obesity.

NCT04768725 ( https://clinicaltrials.gov ) 24th February 2021.

Adipose tissue has recently been recognized as an important endocrine organ that plays a crucial role in energy metabolism and in the immune response in many metabolic tissues. With this regard, emerging evidence indicates that an important crosstalk exists between the adipose tissue and the brain. However, the contribution of adipose tissue to the development of age-related diseases, including Alzheimer's disease, remains poorly defined. New studies suggest that the adipose tissue modulates brain function through a range of endogenous biologically active factors known as adipokines, which can cross the blood-brain barrier to reach the target areas in the brain or to regulate the function of the blood-brain barrier. In this review, we discuss the effects of several adipokines on the physiology of the blood-brain barrier, their contribution to the development of Alzheimer's disease and their therapeutic potential. LINKED ARTICLES: This article is part of a themed issue From Alzheimer's Disease to Vascular Dementia: Different Roads Leading to Cognitive Decline. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.6/issuetoc.

Several studies have reported a relationship between elevated serum adiponectin levels and poor outcomes in patients with heart failure (HF). However, data on the activities of daily living (ADL) in elderly patients with HF are limited.

We evaluated 218 hospitalized elderly (≥65 years) patients with HF who underwent a comprehensive cardiac rehabilitation (CR) program during hospitalization. Serum adiponectin levels were measured before discharge. The Barthel index (BI) score was evaluated at discharge. Low ADL was defined as a BI score < 85.

Serum adiponectin levels were significantly associated with low ADL [p = 0.03; odds ratio (OR), 1.024, per 1.0 μg/mL increase]. In logistic or regression analyses adjusted for age, sex, body mass index, and estimated glomerular filtration rate, high adiponectin levels (≥16.2 μg/mL) were significantly associated with low ADL (p = 0.04; OR, 2.53), malnutrition (p < 0.01; OR, 2.88), and 6-min walk distance (p = 0.04; β = -17.5). In the multivariate analysis adjusted for conventional risk factors of low ADL, high adiponectin levels were also significantly associated with low ADL (p = 0.03; OR, 2.68). In the stepwise forward selection procedure, a high adiponectin level was an independent determinant of low ADL (p = 0.02; R2 = 0.0262). Both net reclassification improvement (0.53; p < 0.01) and integrated discrimination improvement (0.02; p = 0.01) improved significantly after the addition of high adiponectin level to conventional risk factors. In the regression analysis adjusted for age and sex, serum adiponectin levels were significantly (p < 0.0025) negatively associated with abdominal visceral and subcutaneous adipose tissue areas, body weight, body mass index, and serum triglyceride levels.

High serum adiponectin levels were not only significantly associated with an increased risk of low ADL, but also with an increased risk of malnutrition and low physical activity in elderly patients with HF after the in-hospital CR program.

The discovery of new biomarkers that can distinguish Alzheimer's disease (AD) from mild cognitive impairment (MCI) in the early stages will help to provide new diagnostic and therapeutic strategies and slow the transition from MCI to AD. Patients with AD may present with a concomitant metabolic disorder, such as diabetes, obesity, and dyslipidemia, as a risk factor for AD that may be involved in the onset of both AD pathology and cognitive impairment. Therefore, metabolite profiling, or metabolomics, can be very useful in diagnosing AD, developing new therapeutic targets, and evaluating both the course of treatment and the clinical course of the disease. In addition, studying the relationship between nutritional behavior and AD requires investigation of the role of conditions such as obesity, hypertension, dyslipidemia, and elevated glucose level. Based on this literature review, nutritional recommendations, including weight loss by reducing calorie and cholesterol intake and omega-3 fatty acid supplementation can prevent cognitive decline and dementia in the elderly. The underlying metabolic causes of the pathology and cognitive decline caused by AD and MCI are not well understood. In this review article, metabolomics biomarkers for diagnosis of AD and MCI and metabolic risk factors for cognitive decline in AD were evaluated.

The relationship between sex-specific blood biomarkers and memory changes in middle-aged adults remains unclear. We aimed to investigate this relationship using the data from the Framingham Heart Study (FHS). We conducted association analysis, partial correlation analysis, and causal dose-response curves using blood biomarkers and other data from 793 middle-aged participants (≤ 60 years) from the FHS Offspring Cohort. The results revealed associations of adiponectin and fasting blood glucose with midlife memory change, along with a U-shaped relationship of high-density lipoprotein cholesterol with memory change. No significant associations were found for the other blood biomarkers (e.g., amyloid beta protein 42) with memory change. To our knowledge, this is the first sex-specific network analysis of blood biomarkers related to midlife memory change in a prospective cohort study. Our findings highlight the importance of targeting cardiometabolic risks and the need to validate midlife-specific biomarkers that can accelerate the development of primary preventive strategies.

Zika virus (ZIKV) is a pathogenic member of the flavivirus family, with several unique characteristics. Unlike any other arbovirus, ZIKV can be transmitted sexually and maternally, and thus produce congenital syndromes (CZS) due to its neurotropism. This challenges the search for safe active molecules that can protect pregnant women and their fetuses. In this context, and in the absence of any existing treatment, it seemed worthwhile to test whether the known cytoprotective properties of adiponectin and its pharmacological analog, AdipoRon, could influence the outcome of ZIKV infection. We showed that both AdipoRon and adiponectin could significantly reduce the in vitro infection of A549 epithelial cells, a well-known cell model for flavivirus infection studies. This effect was particularly observed when a pre-treatment was carried out. Conversely, ZIKV revealed an ability to downregulate adiponectin receptor expression and thereby limit adiponectin signaling.

This study aimed to investigate the impact of cold adaptation on the neuroendocrine and cardiac substance metabolism pathways in broilers. The broilers were divided into the control group (CC), cold adaptation group (C3), and cold-stressed group (C9), and experimental period was divided into the training period (d 1-35), recovery period (d 36-43), and cold stress period (d 43-44). During the training period, the CC group was reared at ambient temperature, while C3 and C9 groups were reared at 3 °C and 9 °C lower than the ambient temperature, respectively, for 5 h/d at 1 d intervals. During the recovery period, all the groups were maintained at 20 °C. Lastly, during the cold stress period, the groups were divided into two sub-groups, and each sub-group was placed at 10 °C for 12 h (Y12) or 24 h (Y24) for acute cold stimulation. The blood, hypothalamic, and cardiac tissues samples were obtained from all the groups during the training, recovery, and acute stress periods. The results revealed that the transcription of calcium voltage-gated channel subunit alpha 1 C (CACNAIC) was increased in the hypothalamic tissues of the C3 group (p < 0.05). Moreover, compared to the CC group, the serum norepinephrine (NE) was increased in the C9 group (p < 0.05), but insulin (INS) was decreased in the C9 group (p < 0.05). In addition, the transcription of the phosphoinositide-3 kinase (PI3K), protein kinase B (Akt), mammalian target of rapamycin (mTOR), SREBP1c, FASN, ACC1, and SCD genes was down-regulated in the C3 and C9 groups (p < 0.05); however, their expression increased in the C3 and C9 groups after acute cold stimulation (p < 0.05). Compared to the CC group, the transcription of forkhead box O1 (FoxO1), PEPCK, G6Pase, GLUT1, HK1, PFK, and LDHB genes was up-regulated in the C3 and C9 groups (p < 0.05. Furthermore, compared to the CC and C9 groups, the protein and mRNA expressions of heat shock protein (HSP) 70 and HSP90 were significantly increased in the C3 group (p < 0.05). These results indicate that intermittent cold training can enhance cold stress tolerance in broilers by regulating their neuroendocrine and cardiac substance metabolism pathways.

Alzheimer Associated Diabetes Mellitus, commonly known as Type 3 Diabetes Mellitus (T3DM) is a distinct subtype of diabetes with a pronounced association with Alzheimer's disease (AD). Insulin resistance serves as a pivotal link between these two conditions, leading to diminished insulin sensitivity, hyperglycemia, and impaired glucose uptake. The brain, a vital organ in AD context, is also significantly impacted by insulin resistance, resulting in energy deficits and neuronal damage, which are hallmark features of the neurodegenerative disorder. To pave the way for potential therapeutic interventions targeting the insulin resistance pathway, it is crucial to comprehend the intricate pathophysiology of T3DM and identify the overlapped features between diabetes and AD. This comprehensive review article aims to explore various pathway such as AMPK, PPARγ, cAMP and P13K/Akt pathway as potential target for management of T3DM. Through the analysis of these complex mechanisms, our goal is to reveal their interdependencies and support the discovery of innovative therapeutic strategies. The review extensively discusses several promising pharmaceutical candidates that have demonstrated dual drug action mechanisms, addressing both peripheral and cerebral insulin resistance observed in T3DM. These candidates hold significant promise for restoring insulin function and mitigating the detrimental effects of insulin resistance on the brain. The exploration of these therapeutic options contributes to the development of innovative interventions that alleviate the burden of T3DM and enhance patient care.