朱惠莲 博士


柴 智 博士


报告一 NAD 增加和肝脏健康

Lili Yang 博士



Liver is a major organ for energy metabolism. Dysregulation of energy homeostasis is an important risk factor for the formation and progression of fatty liver diseases. We hypothesize that boosting NAD with nicotinamide riboside (NR) can prevent the dysregulation of energy homeostasis in the liver and prevent the formation of fatty liver and liver fibrosis. We did in vivo fatty liver and liver fibrosis mice model and in vitro experiment to test our hypothesis and explore the molecular mechanisms. We found that NR can protect alcohol induced liver steatosis and CCl4 induced liver fibrosis via NAD-SIRT1 pathway. The target for the prevention of liver steatosis by alcohol drinking is by regulating the de-acetylation of PGC1-alpha and mitochondrial function in hepatocytes, and the target for ameliorating liver fibrosis is via regulating de-acetylation of SMADs and collagen synthesis, and inhibiting stellate activation. Overall, our studies show that boosting NAD via NR supplement has protective effect against the formation and progression of fatty liver disease.

报告二 亚麻籽粉经肠-肝-胆汁酸代谢途径对非酒精性脂肪性肝 病改善作用与机制研究

孙桂菊 教授




This study mainly carried out the intervention study of flaxseed powder (FLA) at three doses, constructed the mouse model of simple steatosis (NAFL) and the mouse model of nonalcoholic hepatitis (NASH), and observed the effects of FLA intervention on the gene expression level and protein expression of key enzymes and proteins in lipid metabolism and inflammation, intestinal flora diversity and bile acid profile, To elucidate the mechanism of FLA intervention in the regulation of nonalcoholic fatty liver disease (NAFLD) via intestinal liver bile acid metabolic pathway, and to clarify the role of bile acid-FXR/TGR5 pathway in FLA regulation of NAFLD.

The main results of the study were as follows: FLA intervention had good health benefits in preventing and delaying two-stage NAFL and NASH of NAFLD; Both can significantly improve the lipid metabolism disorder and inflammation in the two stages of NAFLD, and can significantly reduce serum TG, LDL-C, TC and TNF-α. At the same time, it has a significant effect on delaying weight gain. By regulating the structure of intestinal flora, changing the composition of bile acid spectrum, and activating two specific signal pathways FXR-CYP7A1 and TGR5-NF-κB mediated by intestinal FXR and TGR5. Specifically, intestinal FXR activates and inhibits the expression of CYP7A1 in liver through FGFR4, and activates intestinal TGR5, and then inhibits the expression of nfbp65 in liver through TLR4; The two pathways play the role of lipid-lowering and anti-inflammatory respectively. TGR5 gene knockout reverse validation experiment further suggests that these two signal pathways have a certain synergistic effect; TGR5 gene knockout may have no obvious effect on the composition of bile acid spectrum, but TGR5 gene knockout will change the relative abundance of dominant flora in mouse feces and weaken the correlation between intestinal flora and bile acid subfractions.


研究的主要结果为: FLA干预对预防和延缓NAFLD的两阶段NAFL和NASH具有良好的健康效益;并均能够显著改善NAFLD两阶段的脂代谢紊乱和炎症,可显著降低血清TG、LDL-C、TC和TNF-α水平,同时对延缓体重增加均具有显著功效。通过调节肠道菌群结构,改变胆汁酸谱构成,激活两条由肠道FXR和TGR5介导的特异性信号通路FXR-CYP7A1和TGR5-NF-κB,具体表现为肠道FXR激活并通过FGFR4介导抑制肝脏CYP7A1的表达,和激活肠道TGR5,进而通过TLR4介导抑制肝脏NF-κB p65的表达;两个途径分别发挥降脂和抗炎的作用。TGR5基因敲除反向验证实验进一步提示,这两个信号通路具有一定的协同效应;TGR5基因敲除可能对胆汁酸谱构成的影响并不明显,但TGR5基因敲除会造成小鼠粪便中优势菌群相对丰度发生改变,并减弱肠道菌群与胆汁酸亚组分之间的相关性。

报告三 肠道微生物群改变:一种解决食源性二氧化钛纳米颗粒潜 在不良反应的新机制

肖 航 教授



Titanium dioxide (TiO2), a commonly used food additive, contains an appreciable fraction of particles falling in nanoscale. There is increasing concern about the potential unintended health risks associated with foodborne NPs in specific susceptible populations, such as the obese. Herein, we determined the possible adverse effects of orally administered two types of TiO2(30 nm and E171-food grade TiO2) for 12 weeks on two populations of mice, i.e., high-fat diet-treated obese mice and low-fat diet-treated non-obese mice and explore the potential role of gut microbiota in mediating the adverse effects. The results showed that administration of E171 and TiO2 NPs led to the accumulation of TiO2 in mouse kidney and liver dose-dependently, accompanied by the damage to specific cellular organelles in the renal and liver tissues. Furthermore, the TiO2 NPs profoundly modulated the mRNA levels of genes involved in oxidative damage in the liver and kidney. The effects mentioned above were more pronounced in obese mice than in non-obese mice. TiO2 NPs aggravated the obesity-induced abnormality in serum biochemical parameters, related to liver function and lipid metabolism. Additionally, it exacerbated the obesity-induced low-grade colonic inflammation, such as increasing inflammation-relatedcytokines and losing normal morphology in the colon. TiO2NPs further reduced obesity-induced decline in the cecal levels of SCFAs. The results showed that TiO2 NPs led to a significant dysbiosis of gut microbiota with stronger alterations in the obese mice than the non-obese mice. In microbial transplant study, microbiota from the obese mice consuming the high-fat diet with TiO2 NPs led to an increase of pro-inflammatory cytokines and loss of healthy morphology in the colon of health recipient mice, indicating the altered-gut microbiota induced by high-fat diet and TiO2 NPs significantly caused the colonic inflammation. On the other hand, E171 and TiO2 NPs caused adverse effects on the reproductive systems of both male and female mice, such as the sperm and oocytes number decrease, sperm abnormality, pathological change of testes and ovaries, and abnormalities in sex hormone secretion. It is worth noting that the severity of these adverse effects appeared to be greater in the obese mice than non-obese mice. Moreover, TiO2 NPs disordered the expression of genes and proteins related to spermatogenesis, oogenesis, apoptosis, oxidative stress, and steroidogenesis in the gonads of mice, causing reproductive toxicity, especially in the obese ones. Overall, these findings provided valuable new perspectives on the potential adverse effects of foodborne TiO2 engineered NPs among obese vs. non-obese populations.

报告四 中国北方地区老年人膳食炎症指数(DII)与抑郁症的关系

马玉霞 博士

河北医科大学 河北省营养学会 理事长



Objective: Our study aimed to assess the association between the Dietary Inflammatory Index (DII) and depression in the elderly over 55 years in Northern China. and to provide dietary intervention for the depression in the elderly.

Methods: We analyzed the data of 2022 Chinese adults aged 55 and over from a community-based neurological disease cohort study from 2018 to 2019. 6720 participants were included in this cohort study and followed up for 4 years. A validated semi-quantitative food frequency questionnaire was used to assess eating habits at the time of inclusion. The depression was defined according to the geriatric depression scale (GDS). Multiple Logistic regression, mediation effect analysis and Bayesian kernel machine regression (BKMR) were used for analysis by R language software. The social demographics, lifestyle, and health-related factors were adjusted.

Results: Middle-aged and older adults with a higher dietary inflammatory index had a higher prevalence of depression; this association may be mediated by BMI. The BKMR analysis found that pro-inflammatory nutrients were positively correlated with the risk of depressive symptoms, and anti-inflammatory nutrients were positively correlated with the risk of non-depressive symptoms.

Conclusion: Diet is closely related to depression in the elderly. The higher pro-inflammatory potential of diet is associated with a higher risk of depression, and this association may be mediated by BMI. Further study is necessary to verify our findings and clarify the latent mechanism.

报告五 7 个月高脂饮食(HFD)喂养颠覆了干扰素基因刺激因子 (STING)对肥胖相关肝脏炎症的保护作用

Xinlei Guo




Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive depositions of fats in hepatocytes (hepatic steatosis) and progresses its advanced form, non-alcoholic steatohepatitis (NASH) when the liver displays overt inflammatory damage. As a crucial mediator of innate immunity, stimulator of interferon genes (STING) is positively correlated with the degrees of liver inflammation in human patients with NAFLD/NASH. In addition, STING disruption alleviates obesity-induced liver inflammation in mice fed a high-fat diet (HFD, 60% fat calories) for 3 months. However, it is unknown about the effect of STING on liver inflammation in mice upon a prolonged period of HFD feeding, which reflects the long-term course of human obesity. In the present study, wild-type (WT) C57BL/6J mice were fed an HFD or low-fat diet (LFD) for 3 months and examined for changes in liver STING expression in relation to obesity-associated liver inflammation. Next, STING-disrupted (STINGgt) mice and WT mice, at 5-6 weeks of age, were fed an HFD for 3 or 7 months and examined for liver inflammation. Compared with LFD-fed mice, 3 month-HFD-fed mice displayed significantly increased hepatic STING signaling, accompanied with increased phosphorylation states of NFkB p65 and JNK p46. When the effect of STING disruption was examined, the degrees of obesity-associated liver inflammation in STINGgt mice upon HFD feeding for 3 months were significantly lower than those in WT mice, validating a protective role for STING disruption in liver inflammation from mice upon HFD for 3 months. However, upon HFD feeding for 7 months, STINGgt mice displayed significantly increased severity of liver inflammation as evidenced by increased phosphorylation states of NFkB p65 and MAPK p38 relative to WT mice or STINGgt mice upon HFD feeding for 3 months. These results indicate that HFD feeding for 7 months overturns the protective effect of STING disruption on obesity-associated liver inflammation. As such, diets or nutritional approach is of particular importance in managing obesity-associated metabolic diseases.

报告六 调节SEL1L-HRD1 内质网相关降解(ERAD)活性及缓解 内质网(ER)中蛋白质错误折叠的膳食和草药来源的化合物特征分析

Jifeng Yang



Dysregulated production of peptide hormones is the key pathogenic factor of various endocrine diseases. Endoplasmic reticulum (ER) associated degradation (ERAD) is a critical machinery in maintaining ER proteostasis in mammalian cells by degrading misfolded proteins. Dysfunction of ERAD leads to maturation defect of many peptide hormones, such as insulin and vasopressin (AVP), which results in the occurrence of diabetes mellitus and central diabetes insipidus. However, drugs targeting ERAD to regulate the production of peptide hormones are very limited. Dietary and herbal products provide not only nutritional sources, but also alternative therapeutics for chronic diseases. Virtual screening is an effective strategy for identifying protein structure-based interacting compounds extracted from a variety of dietary or herbal sources, which could be served as (pro)drugs for preventing or treating endocrine diseases. Here, we performed a virtual screening by directly targeting SEL1L-HRD1 interface of the most conserved mammalian SEL1L-HRD1 ERAD machinery. Further, we analyzed the 58 top-ranked compounds in vitro, and demonstrated that Cryptochlorogenic acid (CCA), a natural product enriched in mulberry, honeysuckle, etc., showed high affinity with the SEL1L protein on its binding pocket with HRD1. Through structure-based docking, protein expression assays and FACS analysis, we revealed that CCA enhanced ERAD activity and promoted the degradation of misfolded protein both in vitro and in vivo. These results provide us with novel insights into drug discovery strategies targeting ER protein homeostasis, as well as candidate compounds for treating hormone-related diseases.

报告七 综合应激反应(ISR)通路在结肠炎发展过程中调节结肠分泌细胞血清素的分泌

Guanying Bianca Xu



Objectives:Ablation of Hnrnp Iin intestinal epithelial cells (IECs) activates NF-κB signaling, resulting in the early onset of spontaneous colitis and later develop to colorectal cancer. Integrated stress response (ISR) signaling was linked to activation of canonical NF-κB pathway. In this study, we aimed to investigate ISR regulation during inflammation using Hnrnp I knockout mouse model. We hypothesized that increase of cellular stress during colon inflammation would trigger ISR in colonic epiethelia, afftecting epithelial cell dynamics, which intervenes metabolic processes such as serotonin production and cell-cell communication.

Methods:Total RNA was isolated from colon tissue in WT and KO mice. Single-cell RNAseq libraries (biological replicates, n=3) were prepared using Chromium Single-Cell Gene Expression NextGem (v3.1, 10X Genomics). Analyses from raw counts were performed using the Seurat (v3.2.0) R package using default parameters, a computational cell calling algorithm was used to identify cell type using two published annotated mouse cell datasets. Cell-cell communication analysis was performed by CellChat (v1.1.3).

Results:Comparing to WT, proportion of EECs were significantly increased in KO mice colon epithelium. This result was confirmed via immunofluorescence staining of EEC marker, Chromogranin A (CHGA). Total mRNA level of Atf4, the principal regulator of ISR, was significantly increased in EECs of KO mice. Serotonin expression was examined on whole colon and was higher in KO mice colon compared to WT. Amyloid precursor protein (APP) plays eseential role in cell-cell communication initiated from EECs.

Conclusions:Cellular stress originated activates ISR specially in the colonic secretory cell lineages – EECs. The activation of ISR is reflected by the upregulation of Atf4, a pro-survival transcription. Consequently, acvation of ISR promotes differentiation to more EECs. Enterochromaffin cells (ECs) are a type of EECs responsible for serotonin secretion. The increase of EECs on colon epithelium contributes to the increase of ECs, which leads to higher serotonin secretion. Serotonin signaling further regulates APP expression. Hence, the overall manipulation of serotonin secretion through ISR signaling during inflammation may lead to upregulated cell-cell communication via APP initiated from EECs to both intestinal epithelia and immune system, contributing to the following immune responses.

报告八 1,25(OH)2D3对自发性糖尿病大鼠肾脏损伤的改善作用及其机制

Dongxia Wang



Part 1: Ameliorative effect of 1,25(OH)2D3on disorders of glucolipid metabolism in spontaneously diabetic rats.

Part 2: Protective effect of 1,25(OH)2D3on renal injury in spontaneously diabetic rats.

Part 3: The role of NOX4 in oxidative damage of diabetic kidney and the intervention mechanism of 1,25(OH)2D3.

报告九 高脂血症通过视网膜内皮细胞IRE1α-XBP1激活STING通路诱导促炎反应

Zheyao Wen



The incidence of excessive nutrition related diseases such as obesity, type 2 diabetes mellitus (T2DM), cardiovascular disease has been rising in the recent decades. Hyperlipidemia, a common disease associated with excessive nutrition, is a widely-recognized independent risk factor for diabetic microvascular complications. Previous studies demonstrate that microvascular endothelial inflammation caused by chronic hyperlipidemia plays a key role in the pathogenesis of diabetic retinopathy (DR) , which is one of the most prevalent microvascular complications caused by DM. However, the detailed mechanisms on how hyperlipidimia contributes to endothelial inflammation during DR are not fully understood. The STING pathway is an important innate immune signaling pathway. Although STING has been implicated in multiple autoimmune and metabolic diseases, it is not clear whether and how STING was involved in the pathogenesis of DR. In this study, we demonstrated that STING mRNA was highly expressed in mouse retinal vessels by re-analyzing the public single cell RNA-seq database. Interestingly, our results demonstrated that STING and p-TBK1 protein levels in mouse retinal endothelial cells were significantly increased in mice fed with high fat diet compared with chow diet. Then we showed that palmitic acid (PA) treatment on human retinal vascular endothelial cells (HRVECs) in vitro induced mitochondrial DNA leakage into the cytosol, induced TBK1 protein phosphorylation and IFN-β mRNA expression, indicating the activation of STING pathway. As STING is localized to the ER, we analyzed the relationship between STING activation and ER stress. In HRVECs, we showed that STING pathway was activated under ER stress in vitro, but attenuated when IRE1α was abolished by genetic deletion or pharmacological inhibition. Taken together, our findings reveal that STING signaling plays an important role in mediating lipotoxicity-induced endothelial inflammatory and injury, while IRE1α-XBP1 signaling exaggerated STING signaling. Thus, targeting IRE1α or STING pathways provides candidate therapeutics for treating DR as well as other microangiopathy through alleviating endothelial inflammation.

报告十 叶酸和二十二碳六烯酸通过端粒改善轻度认知障碍老年人认知功能的作用及机制

Mengyue Li



Objective: Mild cognitive impairment (MCI) is the early status of Alzheimer’s disease, (AD). Delaying the decline of cognitive function in the elderly with MCI is an important means to prevent AD. The objective of this study was to discuss the mediating effect of telomere in the relationship between folic acid (FA) or docosahexaenoic acid (DHA) and cognitive function, whether the combined intervention of FA and DHA has a synergistic effect on the improvement of cognitive function in the elderly with MCI, and whether they can ameliorate the cognitive function of the elderly with MCI by delaying telomere shorting.

Method: In the case-control study, 280 MCI elderly and 280 cognitively normal elderly were matched according to the same sex, two years in age and one year in education. The cognitive function was estimated by the scores of mini mental state examination (MMSE). Serum folate, Hcy, plasma DHA, leukocytes telomere length (LTL) and mitochondrial copy number were detected. The relationships between folate, Hcy, DHA, LTL, mitochondrial copy number and cognitive function were analyzed by Pearson correlation analysis and logistic regression. Structural equation models were used to analyze the mediating effect of LTL in the relationship between FA or DHA and cognitive function.

In the randomized double-blind controlled trial, 280 elderly patients with MCI were randomly divided into FA+DHA group (800 μg FA + 800 mg DHA/d), FA group (800 μg FA/d), DHA group (800 mg DHA/d) and Placebo group, with 70 subjects in each group. Cognitive function, peripheral folate, Hcy, DHA, LTL, telomere related protein mRNA expression, oxidative stress levels, mitochondrial function, p53 protein levels and p53-mRNA expression were measured at baseline and 12 months. Mixed linear models were used to analyze the changes of the above indexes after 12 months of intervention.

Result: The results of case-control study showed that, the serum folate and plasma DHA levels, LTL and mitochondrial copy numbers of MCI group were lower and the serum Hcy levels of MCI group was higher (P < 0.05), comparing with control group. The levels of folate, DHA, LTLs and numbers of mitochondrial copy number were positively correlated with MMSE scores, while the levels of Hcy was negatively correlated with LTL (P <0.05). Higher levels of folate, DHA, LTL and mitochondrial copy number were the protective factors of MCI, while higher levels of Hcy was a risk factor of MCI. The levels of folate, LTL and Hcy were negatively correlated, and the levels of LTL and DHA were positively correlated (P <0.05). LTL played mediating roles in the relationship of Hcy and cognitive function, and DHA and cognitive function (P <0.05), and the mediating effects were 21.90% and 12.10%. Hcy levels and LTL played a tandem mediating role in the relationship between folate levels and MMSE scores (P <0.05).

The results of randomized double-blind controlled trial showed that, after a 12 months intervention, the full scale IQ (FIQ), verbal IQ (VIQ), performance IQ (PIQ), information, arithmetic, similar and block diagram scores in FA + DHA group, the FIQ, VIQ, information, arithmetic and similar scores in FA group and DHA group, were higher, comparing with placebo group (P <0.05). The FIQ, PIQ and block diagram scores in FA+DHA group were higher, comparing with FA group or DHA group (P <0.05). The LTL in FA + DHA group, FA group and DHA group were longer; the expression of TRF2-mRNA in FA + DHA group, FA group and DHA group were lower; the levels of hydrogen peroxide in FA+DHA group were lower; the ability of inhibiting superoxide anion in FA+DHA group and FA group were higher; the content of genomic 8-oxoG in FA+DHA group, FA group and DHA group were lower; the mitochondrial copy number in FA+DHA group, FA group and DHA group were higher; the mitochondrial deletion in FA+DHA group and FA group were less; the levels of p53 in FA+DHA group, FA group and DHA group were lower, comparing with placebo group (P < 0.05).

Conclusion: The levels of folate, DHA, Hcy and LTL were related to cognitive function of the elderly. Folic acid, DHA can improve the cognitive function of MCI elderly. The effect of folic acid and DHA combined intervention is better than that of folic acid and DHA alone. Folic acid and DHA may play a synergistic role in improving the cognitive function of MCI elderly. Folic acid and DHA may improve cognitive function of MCI elderly by delaying telomere shortening.




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