scholarly journals Citrus reticulatae pericarpium Extract Decreases the Susceptibility to HFD-Induced Glycolipid Metabolism Disorder in Mice Exposed to Azithromycin in Early Life

2021 ◽  
Vol 12 ◽  
Author(s):  
Hanqi Lu ◽  
Yanting You ◽  
Xinghong Zhou ◽  
Qiuxing He ◽  
Ming Wang ◽  
...  

BackgroundStudies have shown that gut microbe disorder in mice due to early-life antibiotic exposure promotes glycolipid metabolism disorder in adulthood. However, the underlying mechanism remains unclear and there is not yet an effective intervention or treatment for this process.PurposeThe study investigated whether early-life azithromycin (AZT) exposure in mice could promote high-fat diet (HFD)-induced glycolipid metabolism disorder in adulthood. Moreover, the effect of citrus reticulata pericarpium (CRP) extract on glycolipid metabolism disorder via regulation of gut microbiome in mice exposed to antibodies early in life were investigated.Methods and ResultsThree-week-old mice were treated with AZT (50 mg/kg/day) via drinking water for two weeks and then were fed a CRP diet (1% CRP extract) for four weeks and an HFD for five weeks. The results showed that early-life AZT exposure promoted HFD-induced glycolipid metabolism disorder, increased the levels of inflammatory factors, promoted the flora metabolism product trimethylamine N-oxide (TMAO), and induced microbial disorder in adult mice. Importantly, CRP extract mitigated these effects.ConclusionTaken together, these findings suggest that early-life AZT exposure increases the susceptibility to HFD-induced glycolipid metabolism disorder in adult mice, and CRP extract can decrease this susceptibility by regulating gut microbiome.

Author(s):  
Dan-Dan Wang ◽  
Fang Wu ◽  
Ling-Yu Zhang ◽  
Ying-Cai Zhao ◽  
Cheng-Cheng Wang ◽  
...  

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Yanhua Zhao ◽  
Lili Huang ◽  
Huan Xu ◽  
Guangxi Wu ◽  
Mengyi Zhu ◽  
...  

Postoperative cognitive dysfunction (POCD) increases morbidity and mortality after surgery. But the underlying mechanism is not clear yet. While age is now accepted as the top one risk factor for POCD, results from studies investigating postoperative cognitive functions in adults have been controversial, and data about the very young adult individuals are lacking. The present study investigated the spatial reference memory, IL-1β, IL-6, and microglia activation changes in the hippocampus in 2-month-old mice after anesthesia and surgery. We found that hippocampal IL-1βand IL-6 increased at 6 hours after surgery. Microglia were profoundly activated in the hippocampus 6 to 24 hours after surgery. However, no significant behavior changes were found in these mice. These results indicate that although anesthesia and surgery led to neuroinflammation, the latter was insufficient to impair the spatial reference memory of young adult mice.


2018 ◽  
Vol 1 (4) ◽  
Author(s):  
Wenting Shi ◽  
Jin Li ◽  
Pengyi Zhang

Objective  To observe the dynamic changes of gut microbiome in mice before and after different intensities of treadmill exercises, and to explore the effects of different intensities of treadmill exercises on gut microbiome of atherosclerotic (AS) mice. Methods  The 50 male ApoE-/- mice aged 8 weeks were randomly divided into 2 groups, 10 mice in the general feeding group and the other 40 mice in the AS group, which were fed with normal and high-fat diet for 4 weeks respectively. Weight and blood test were taken before and after 4 weeks feeding. The serum Triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein (HDL) levels were examined by blood test in ApoE-/- mice model, and atherosclerotic disease degeneration score of adult mice was used to determine the success of modeling after 4 weeks feeding. Then two mice selected from the normal and high-fat group respectively selected to test the maximum oxygen uptake (VO2 max) by the reformative Bedford method, and the running platform speed and slope corresponding to 30%, 50% and 70%VO2 max were determined. The 40 AS mice were randomly divided into the model blank group, the low-intensity exercise group, the medium-intensity exercise group and the high-intensity exercise group according to their weight for 4 weeks of exercises, respectively. The low-intensity exercise group was 30% VO2 max, with a slope of 10 degrees and a speed of 10 m/min. The medium intensity exercise group was 50% VO2 max with a slope of 10 degrees and a speed of 15 m/min. The high-intensity exercise group was 70% VO2 max with a slope of 10 degrees and a speed of 20 m/min. The exercises were performed for 4 weeks, 5 days a week, 20 minutes a day. The fresh feces were collected from 5 groups of mice before and after 4 weeks treadmill exercises. The number of gut Lactobacillus, Bacteroides, Firmicutes, Bifidobacterium, Verrucomicrobiaceae, Akkermansia , Escherichia coli, Collinsella and Clostridium in AS mice were analyzed by 16s sequencing.  Results 1. The TG, TC and LDL-C were significantly increased in the blood serum of the mice after the modeling, and the HDL-C was decreased, and the atherosclerotic disease degeneration score was significantly increased in the adult mice, and the modeling was successful. 2. The different intensity treadmill exercises can increase the number of gut probiotics in mice and decrease the number of harmful bacteria. The beneficial bacteria in gut tract of AS mice with moderate intensity of 50% VO2max was observed in the experiment: Bacteroides, Bifidobacterium and Verrucomicrobiaceae, Akkermansia were significantly increased, P<0.05. The harmful bacteria:Lactobacillus, Escherichia coli, Collinsella and Clostridium were significantly decreased, P<0.05. The ratio of Firmicutes / Bacteroidetes was increased. Conclusions  1. High-fat diet can lead to AS in ApoE-/- mice. 2. The different intensity treadmill exercises can reduce the weight of AS mice. 3. The number and abundance of probiotics of gut microbiome of AS mice could be promoted by different intensity treadmill exercises, among which the medium intensity aerobic exercise can significantly increase the number of beneficial bacteria such Bacteroidetes, Bifidobacteria, Verrucomicrobiaceae and Akkermansia, meanwhile, the structure of gut microbiome in AS mice was improved as well.


2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Haoyang Zhao ◽  
Kangyu Jin ◽  
Chaonan Jiang ◽  
Fen Pan ◽  
Jing Wu ◽  
...  

AbstractThe pathophysiology of major depressive disorder (MDD) remains obscure. Recently, the microbiota-gut-brain (MGB) axis’s role in MDD has an increasing attention. However, the specific mechanism of the multi-level effects of gut microbiota on host metabolism, immunity, and brain structure is unclear. Multi-omics approaches based on the analysis of different body fluids and tissues using a variety of analytical platforms have the potential to provide a deeper understanding of MGB axis disorders. Therefore, the data of metagenomics, metabolomic, inflammatory factors, and MRI scanning are collected from the two groups including 24 drug-naïve MDD patients and 26 healthy controls (HCs). Then, the correlation analysis is performed in all omics. The results confirmed that there are many markedly altered differences, such as elevated Actinobacteria abundance, plasma IL-1β concentration, lipid, vitamin, and carbohydrate metabolism disorder, and diminished grey matter volume (GMV) of inferior frontal gyrus (IFG) in the MDD patients. Notably, three kinds of discriminative bacteria, Ruminococcus bromii, Lactococcus chungangensis, and Streptococcus gallolyticus have an extensive correlation with metabolome, immunology, GMV, and clinical symptoms. All three microbiota are closely related to IL-1β and lipids (as an example, phosphoethanolamine (PEA)). Besides, Lactococcus chungangensis is negatively related to the GMV of left IFG. Overall, this study demonstrate that the effects of gut microbiome exert in MDD is multifactorial.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jamie L. Young ◽  
Xiaofang Yan ◽  
Jianxiang Xu ◽  
Xinmin Yin ◽  
Xiang Zhang ◽  
...  

Abstract Exposure to the environmental toxicant cadmium (Cd) contributes to the development of obesity-associated diseases. Obesity is a risk factor for a spectrum of unhealthy conditions including systemic metabolic dyshomeostasis. In the present study, the effects of whole-life exposure to environmentally-relevant concentrations of Cd on systemic essential metal distribution in adult mice fed a high-fat diet (HFD) were examined. For these studies, male and female mice were exposed to Cd-containing drinking water for >2 weeks before breeding. Pregnant mice and dams with offspring were exposed to Cd-containing drinking water. After weaning, offspring were continuously exposed to the same Cd concentration as their parents, and divided into HFD and normal (low) fat diet (LFD) groups. At 10 and 24 weeks, mice were sacrificed and blood, liver, kidney and heart harvested for metal analyses. There were significant concentration dependent increases in Cd levels in offspring with kidney > liver > heart. Sex significantly affected Cd levels in kidney and liver, with female animals accumulating more metal than males. Mice fed the HFD showed > 2-fold increase in Cd levels in the three organs compared to similarly treated LFD mice. Cadmium significantly affected essential metals levels in blood, kidney and liver. Additionally, HFD affected essential metal levels in these three organs. These findings suggest that Cd interacts with HFD to affect essential metal homeostasis, a phenomenon that may contribute to the underlying mechanism responsible for the development of obesity-associated pathologies.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1749-1749
Author(s):  
Jin-Ran Chen ◽  
Oxana Lazarenko ◽  
Michael Blackburn ◽  
Eugenia Carvalho ◽  
Kartik Shankar ◽  
...  

Abstract Objectives It has been recognized that mechanical stresses associated with physical activity (PA) have beneficial effects on increasing bone mineral density (BMD) and improving bone quality in humans and animal models. On the other hand, in rodents, high fat diet (HFD) and obesity increase bone marrow adiposity leading to increased production of pro-inflammatory cytokines that activate RANKL-induced bone resorption. In the current study, we investigated whether short-term increased PA via access to voluntary wheel running during early life has persistent effects on HFD-induced bone resorption. Methods Sixty (60) four-week-old male C57BL6/J mice were divided into two groups; without or with PA, access to voluntary running wheel (7 to 8 km per day) for 4 wks, with ad libitum access to control diet for all animals. After 4 wks with or without PA, mice were further subdivided into control diet or HFD groups for 8 wks, before all animals were switched back to control diet for an additional 4 wks. Mice from the HFD groups were significantly heavier, with more adiposity vs. control group at the 12 wk study time point, and returned to levels of mice with continues control diet at the 16 wk study time point. Results Using peripheral quantitative CT (pQCT) and micro-CT scan on tibias ex vivo, we determined that trabecular BMD and bone volume were significantly increased in animals after 4 wks of PA and control diet compared to sedentary animals without access to wheels. Eight weeks of HFD deteriorated bone development in mice, micro-CT showed 9% significant reduction on percentage of bone volume, and pQCT analysis showed 6% significant reduction of trabecular bone density of mice compared with those standard diet mice. Unexpectedly, early life PA exacerbated HFD-induced trabecular bone loss in adult mice. Early life PA accelerated HFD-induced osteoclastogenesis in adult mice. In accordance with these data, signal transduction studies revealed that HFD-induced Ezh2 and NFATc1, and IRF8 expression were amplified in non-adherent hematopoietic cells. Conclusions Increased PA in early life is capable of increasing bone mass; however, it alters the HFD-induced bone marrow hematopoietic cell differentiation program to exacerbate bone resorption if PA is halted. Funding Sources Supported in part by USDA-ARS Project 6026–51,000-010–05S.


Life Sciences ◽  
2021 ◽  
Vol 270 ◽  
pp. 119133
Author(s):  
Heng Tang ◽  
Qingfu Zeng ◽  
Ting Tang ◽  
Yunjie Wei ◽  
Peng Pu

2020 ◽  
Author(s):  
Qingfu Zeng ◽  
Heng Tang ◽  
Ting Tang ◽  
Peng Pu

Abstract Background: Kaempferide (Ka, 3,5,7-trihydroxy-4′-methoxyflavone), an active ingredient of Tagetes erecta L has been demonstrated to possess many pharmacological effects, including antioxidant, anti-inflammation, anticancer and antihypertension in previous study. However, there is no evidence of Ka on metabolic disorder in former studies. This study investigated the effects of Ka on glycolipid metabolism and explored the underlying mechanisms of action in vivo and vitro. Methods: High-fat diet (HFD) was used to induce the model of glycolipid metabolism disorder in mice.The hypolipidemic and hypoglycemic effect was detected by several indicators, like blood sample analysis blood glucose, serum insulin, HOMA index and intraperitoneal glucose tolerance tests (IPGTT). The signaling pathways of lipid metabolism (PPARγ/LXRα/ABCA1) and glucose metabolism (PPARγ/PI3K/AKT) were evaluated using Real-Time PCR and Western blot. The primary culture of hepatocytes was prepared to confirm the target of Ka by co-culturing with PPARγ agonist or inhibitor.Results: Administration of Ka at a dose of 10mg/kg for 16 weeks effectively attenuated obesity, hyperlipidemia, hyperglycemia and insulin resistance in HFD mice. Further studies revealed the hypolipidemic and hypoglycemic effects of Ka depended on the activation of PPARγ/LXRα/ABCA1 pathway and PPARγ/PI3K/AKT pathway, respectively. The primary hepatocyte test, co-cultured with PPARγ agonists or inhibitors, further confirmed the above signaling pathway and key protein. Conclusion: Ka played an important role in improving glycolipid metabolism disorder, which were causally associated with weight loss. The underlying mechanisms might are associated with the activation of PPARγ and its downstream signaling pathway. Our study helped to understand the pharmacological actions of Ka, and provides theoretical basis for Ka in the effective treatment of obesity, diabetes and other metabolic diseases.


2019 ◽  
Vol 172 (1) ◽  
pp. 98-108
Author(s):  
Pei Wang ◽  
Guangming Liu ◽  
Yali Nie ◽  
Shengna Han ◽  
Jiangfeng Li ◽  
...  

Abstract Pregnane X receptor (PXR), which can be activated by xenobiotic chemicals (including pediatric drugs), plays a key role in the regulation of drug-processing genes (DPGs). The induction of DPGs due to PXR activation may reduce therapeutic efficacy or cause toxicity. This work aims to demonstrate the impact of pregnenolone 16α-carbonitrile (PCN)-mediated PXR activation during early life on DPGs expression and drug sensitivity in adulthood, as well as the underlying mechanism. In this study, mice were sacrificed at postnatal day 60 to detect the hepatic expression of selected DPGs and histone modifications in the Cyp3a11 promoter. We found that all doses of PCN treatment (50–200 mg/kg/day) at postnatal days 5–8 resulted in persistently increased CYP2B10 expression, whereas only high doses of PCN treatment (150 and 200 mg/kg/day) persistently induced the expression of CYP3A11, 1A2, and UGT1A1. We also demonstrated that PCN treatment before postnatal day 15 had a long-term impact on the expression of CYP3A11, 2B10, ABCC4, and PAPSS2. Additionally, elevated expression of CYP3A11, SULT2A1, UGT1A1, and PAPSS2 was observed in PCN-treated groups at days 25–28. Attenuated inducibility of CYP3A11 by PCN was seen in the primary hepatocytes derived from PCN-pretreated mice. Moreover, enhanced H3K4me3 level and reduced H3K27me3 level in the PXR response elements (PXREs) of the Cyp3a11 promoter may contribute to the persistent upregulation of CYP3A11 by neonatal PCN treatment. Overall, our study suggests that PXR activation during early life could persistently alter the hepatic expression of DPGs and epigenetic memory may be an underlying mechanism in mice.


2018 ◽  
Vol 1 (3) ◽  
Author(s):  
Jing Xiao

Objective C57 mice were fed with high-fat diet. After the pathological features were detected, a group of C57 high-fat diet mice were randomly selected for eight weeks aerobic and anti-resistance exercise. To observe the effect of exercise on liver glucose and lipid metabolism in mice fed with high fat. To explore the effect of exercise on liver glucose and lipid metabolism disorder caused by high fat feeding, to provide the direction and evidence for the treatment and rehabilitation of fatty liver and other diseases caused by high fat diet. C57 mice were fed with high-fat diet. After the pathological features were detected, a group of C57 high-fat diet mice were randomly selected for eight weeks aerobic and anti-resistance exercise. To observe the effect of exercise on liver glucose and lipid metabolism in mice fed with high fat. To explore the effect of exercise on liver glucose and lipid metabolism disorder caused by high fat feeding, to provide the direction and evidence for the treatment and rehabilitation of fatty liver and other diseases caused by high fat diet. Methods 30 male C57 mice were 8 weeks old, with an average weight of 20.02 ±0.06 g. The purchased mice were randomly divided into C57 diet group (n = 10) and high-fat diet group (n = 20). A pathological model of hepatic glycolipid metabolism disorder was established by high-fat feed feeding. The success of the model was measured by calculating the area under the blood glucose curve. After modeling, the C57 mice were randomly divided into high fat group and high fat exercise group, with 10 mice in each group. The mice in high fat exercise group were trained 6 days a week for 8 weeks. At the end of the exercise, the three groups were uniformly selected. Results 1. Compared with the normal diet quiet group, there was a significant difference in the area under the blood glucose curve in the high-fat diet quiet group (p < 0. 01). Compared with the quiet high-fat diet group, there was a significant difference in the area under the blood glucose curve after intraperitoneal injection of glucose in the high-fat diet exercise group (p < 0. 05). After two weeks of high fat diet feeding, the body weight of the quiet group was significantly higher than that of the quiet group fed with normal diet (p < 0.05). After two weeks exercise training of high-fat mice, the body weight of high-fat exercise group was significantly lower than that of quiet high-fat mice (p < 0.05). Compared with the normal diet group, the liver weight and liver weight of the high-fat quiet group increased (p < 0 01), while the liver weight and liver / body weight of the high-fat exercise group were lower than those of the high-fat quiet group (p < 0 05). The liver AST (aspartate amino transferase) and ALT(Alanine transferase) in the High-fat diet quiet group were significantly higher than those in the normal diet quiet group (p < 0. 01). The ALT (alanine transferase) in high-fat diet exercise group was lower than that in quiet high-fat diet group (p < 0.05). Conclusions 16-week high-fat diet can establish a pathological model of hepatic glycolipid metabolism disorder. Hyper-insulinemia, hyper-lipidemia and other pathological phenomena will occur in mice. 8 weeks aerobic combined with anti-exercise intervention can improve hepatic glycolipid metabolism disorder and liver function.


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