Chronic low-grade inflammation of visceral adipose tissue can cause obesity-associated insulin resistance, leading to metabolic syndrome. However, anti-inflammatory drugs and those for obesity management can lead to serious side effects such as abnormal heart rate and blood pressure. Consequently, this study aimed to explore the therapeutic potential of electroacupuncture stimulation (ES) for obesity and associated chronic inflammation. Sprague-Dawley male rats were fed a high-fat diet (HFD) for ten weeks to build an obesity model, and half of the diet-induced obesity (DIO) rats were received ES. The levels of inflammatory factors were detected by ELISA and qPCR analysis. The nerve-associated macrophages were marked with immunofluorescence staining. The molecular mechanism of NLRP3 inflammasome in ES was determined by the NLRP3 inflammasome activation model. Compared to HDF rats, ES showed decreased body weight and chronic inflammatory damage. Specifically, this occurred via a decrease in monoamine oxidase-A (MAOA) expression, which suppressed noradrenaline degradation. MAOA is expressed in nerve-associated macrophages (NAMs), and ES attenuated NAMs by suppressing the NLRP3 inflammasome. The NLRP3 agonist blocked the noradrenaline degradation-reducing effect of ES, and an increase in lipolysis via the inhibition of the NLRP3 inflammasome attenuated NAMs. Thus, our findings suggest that ES induced lipolysis via activation of the NLRP3 inflammasome in nerve-associated macrophages (NAMs), independently of sympathetic nervous system activity.
Abstract Microglia, the main immune cell of the central nervous system (CNS), categorized into M1-like phenotype and M2-like phenotype, play important roles in phagocytosis, cell migration, antigen presentation, and cytokine production. As a part of CNS, retinal microglial cells (RMC) play an important role in retinal diseases. Diabetic retinopathy (DR) is one of the most common complications of diabetes. Recent studies have demonstrated that DR is not only a microvascular disease but also retinal neurodegeneration. RMC was regarded as a central role in neurodegeneration and neuroinflammation. Therefore, in this review, we will discuss RMC polarization and its possible regulatory factors in early DR, which will provide new targets and insights for early intervention of DR.
Obesity often coexists with diabetes, especially abdominal obesity, recognized as a risk factor for diabetic complications. Diabetic retinopathy (DR), as one of the most common microvascular complications of diabetes, may be associated with these indices. Lipid accumulation product (LAP) and Chinese visceral obesity index (CVAI) are novel visceral obesity indicators, which have been proven to be an influential factor predicting type 2 diabetes (T2DM). However, the correlation among LAP, CVAI, and DR still lacks systematic research in T2DM. The study aimed to explore the relationship among LAP, CVAI levels in different DR stages of T2DM patients and the diagnostic efficacy of LAP and CVAI for DR.A total of 263 participants were recruited in this cross-sectional study. We enrolled 169 patients with T2DM, divided into the non-DR group (NDR, n = 61), non-proliferative DR group (NPDR, n = 55), and proliferative DR group (PDR, n = 53). And we also enrolled 94 healthy control participants. We collected demographic, anthropometric, and biochemical data on each subject. LAP and CVAI are calculated according to different formulas for men and women.Compared with the control group, LAP and CVAI were significantly higher (P < 0.05). After adjusting for confounding factors, LAP (OR: 1.029, 95CI%: 1.010-1.049, P < 0.05), WC (OR: 1.073, 95CI%: 1.009-1.141, P < 0.05) and CVAI (OR: 1.017, 95CI%: 1.000-1.033, P < 0.05) were all associated with an increased risk of DR. Furthermore, increased LAP (OR: 1.020, 95% CI: 0.100-0.290) is associated with DR severity (P < 0.001). Moreover, the LAP had the most significant area under the receiver operating characteristics (ROC) curve (AUC) (AUC = 0.728, 95% CI: 0.653-0.804).A high LAP is associated with an increased risk of DR in T2DM patients, and the LAP index appears to be a good predictor of DR risk and severity in patients with T2DM, compared with BMI, WC, and CVAI.
Human breast milk, the best source of nutrition for newborns, can reduce the incidence of bronchopulmonary dysplasia (BPD). Bioactive peptides are important components of human breast milk. However, their function in BPD are unclear. We screened a novel peptide (named MDABP) in the breast milk of mothers of premature infants, which has beneficial effects in experimental BPD. This study aimed to investigate the role and mechanism of MDABP in vivo and vitro. Newborn Sprague-Dawley (SD) rats were exposed to normoxia (21 % O2) or hyperoxia (85 % O2) and injected with MDABP or PBS from postnatal days 1 to 7 (PN1-PN7). On PN7, the lungs were harvested for histological and biochemical analysis. The results revealed that MDABP improved alveolar simplification and pulmonary vascular retardation, promoted alveolar epithelial cell (AEC) proliferation and inhibited cell apoptosis. In vitro, MDABP, but not scrambled MDABP, promoted cell proliferation and reduced cell injury without obvious toxicities. RNA-sequencing in A549 cells showed a total of 214 genes were significantly differentially expressed between the MDABP + hyperoxia and hyperoxia groups, including 80 upregulated and 134 downregulated genes. KEGG pathway analysis showed that significant differentially expressed genes were related to the ferroptosis signaling pathway. Rescue experiments showed that MDABP reduced the hyperoxia- and ferroptosis-induced damage to AEC by decreasing the levels of Fe2+ and ROS and increasing the levels of GSH and GPX4. The p-value of the above experiment was less than 0.05, which was considered statistically significant. This study provides a new basis for developing treatments for BPD.
Abstract Background The study and synthesis of membrane organelles are becoming increasingly important, not only as simplified cellular models for corresponding molecular and metabolic studies but also for applications in synthetic biology of artificial cells and drug delivery vehicles. Lipid droplets (LDs) are central organelles in cellular lipid metabolism and are involved in almost all metabolic processes. Multiple studies have also demonstrated a high correlation between LDs and metabolic diseases. During these processes, LDs reveal a highly dynamic character, with their lipid fraction, protein composition and subcellular localisation constantly changing in response to metabolic demands. However, the molecular mechanisms underlying these functions have not been fully understood due to the limitations of cell biology approaches. Fortunately, developments in synthetic biology have provided a huge breakthrough for metabolism research, and methods for in vitro synthesis of LDs have been successfully established, with great advances in protein binding, lipid function, membrane dynamics and enzymatic reactions. Aims and methods In this review, we provide a comprehensive overview of the assembly and function of endogenous LDs, from the generation of lipid molecules to how they are assembled into LDs in the endoplasmic reticulum. In particular, we highlight two major classes of synthetic LD models for fabrication techniques and their recent advances in biology and explore their roles and challenges in achieving real applications of artificial LDs in the future.
Abstract Background and aims: Obesity often coexists with diabetes has been recognized as a risk factor for diabetic complications. Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes, and the metabolic syndrome (MetS) is one of the most common symptoms of diabetes. The purpose of this study was to explore the relationship between DR and some induces, including NC, CVAI, PWNC and so on; as well as the relationship between DR and MetS. Methods: From 2018 to 2019, a total of 562 diabetics from the Hulan District of Harbin, Heilongjiang, were selected and completed a questionnaire survey. The questionnaire included basic patient information, anthropometric parameters, blood pressure, biochemical parameters and fundus photography results. Results: In both men and women, a one standard deviation (SD) increase in NC、CVAI and PWNC was not associated with the prevalence of DR (P>0.05). However, in both men and women, a one SD increase in NC、CVAI and PWNC was significantly associated with the prevalence of MetS (P<0.05). These association were all adjusted for potential confounding factors. Moreover, DR was not associated with MetS(P>0.05). Conclusions: NC, CVAI and PWNC are associated with the prevalence of MetS. NC in men and CVAI in women had the largest area under the ROC curve compared to the other induces, which may be convenient and valuable anthropometric measurements for early prevention of MetS. However, these induces had no association with DR and there is no relationship between DR and MetS.
Background: Diabetes may increase the risk of conversion of mild cognitive impairment (MCI) to dementia. Lipid accumulation product (LAP), an index of visceral obesity, has been shown to be a powerful predictor of insulin resistance and type 2 diabetes (T2D). However, little attention has been paid to the relationship between LAP and MCI in T2D. Objective: We aimed to investigate the association between the LAP index and MCI in patients with T2D. Methods: In total, 220 hospitalized patients with T2D, including 113 MCI patients and 107 patients with normal cognition, were enrolled in this cross-sectional study. We collected demographic, anthropometric, and biochemical data on each subject. The LAP index was calculated according to the following formulas: [waist circumference (WC) (cm) – 65]×triglyceride (TG) (mmol/L) for males and [WC (cm) – 58] ×TG (mmol/L) for females. Results: Compared with patients with normal cognition, MCI patients were older and had a higher LAP index, WC, body mass index, and glycosylated hemoglobin A1c level, as well as a lower Montreal Cognitive Assessment score and education level (p < 0.05). After adjusting for confounding factors, LAP index was associated with MCI (OR = 1.047, 95% CI = 1.031–1.063, p < 0.01). The area under the ROC curve (AUC) for the LAP index was higher than that for WC and BMI. Conclusion: A high LAP index is associated with an increased risk of MCI in T2D patients. The LAP index appears to be a good indicator of risk of MCI in patients with T2D.
Abstract Diabetic retinopathy (DR), a serious microvascular complication of diabetes, is a leading cause of blindness in adults. The pathogenesis of DR involves a variety of tissues and complex mechanisms, such as inflammation, oxidative stress, optic neurodegeneration, and autophagy. Nowadays, microRNAs (miRNAs), a novel group of non-coding small RNAs, have been extensively studied and recognized to play a key role in the pathogenesis of DR through aforementioned pathways. Furthermore, some miRNAs have been proposed as biomarkers that may be utilized to screen for DR. Also, miRNAs are a new therapy for DR. In this review, we summarize several miRNAs and, their roles in the pathogenesis of DR. miRNAs, as potential pharmacological targets for the diabetic retinopathy, may provide new insights for the treatment of DR.
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