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CHEMOSPHERE · 2018 · IF 4.427

Effects of perinatal exposure to BPA and its alternatives (BPS, BPF and BPAF) on hepatic lipid and glucose homeostasis in female mice adolescent offspring

Zhiyuan Meng,Dezhen Wang,Sen Yan,Ruisheng Li,Jin Yan,Miaomiao Teng,Zhiqiang Zhou,Wentao Zhu

The widespread application of bisphenols (BPs) makes them ubiquitous in the natural environment and poses many potential risks. In this study, we examined the effects of perinatal exposure to BPA and its 3 alternatives (BPS, BPF, and BPAF) on lipid and glucose homeostasis in female mice adolescent offspring . Specifically, BPA exposure promoted the expression of hepatic lipid synthesis and fatty acid accumulation genes, resulting in a significant increase in 2 free fatty acids contents. BPS exposure caused an increase in 6 free fatty acids and triglyceride contents through promoting the expression of fatty acid synthesis, triglyceride synthesis and fatty acid accumulation genes and inhibiting the expression of fatty acid β-oxidation genes. Interestingly, BPAF exposure showed completely opposite effects on hepatic lipid metabolism compared to BPS exposure. 9 free fatty acids and triglycerides contents in the liver were significantly reduced. In particular, BPF exposure caused decreases in 2 free fatty acids contents, but no significant changes were found in the genes for lipid metabolism. In addition, unlike BPA and BPF exposure, BPS and BPAF exposure also resulted in significant increases in glucose and glycogen contents in the liver by activation of Fxr-Sh p pathway and glycolysis, and inhibition of gluconeogenesis. The results showed that compared to BPA and BPF exposure, BPS and BPAF exposure significantly regulated the expression of genes related to glucose and lipid metabolism and severely interfered with hepatic lipid and glucose homeostasis. This suggested that we should thoroughly evaluate the potential health risks of BPA and its alternatives.

CAS / MDL: 7789-20-0
研究领域: 环境科学 · 分子生物学 · 毒理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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CHEMOSPHERE · 2018 · IF 4.427

Impaired lipid and glucose homeostasis in male mice offspring after combined exposure to low-dose bisphenol A and arsenic during the second half of gestation

Dezhen Wang,Wentao Zhu,Sen Yan,Zhiyuan Meng,Jin Yan,Miaomiao Teng,Ming Jia,Ruisheng Li,Zhiqiang Zhou

In this study, we used a 1 H NMR based metabolomics strategy combined with gene expression analysis to determine the combined effects of gestational exposure of mice to BPA (10 μg/kg body weight by subcutaneous injection) and arsenic (10 ppb sodium arsenite in drinking water). Results showed that exposure to either BPA or, arsenic or their combination induced age-dependent metabolic disruptions in male mice offspring , and the combined exposure could exacerbate the metabolic changes induced by either BPA or arsenic alone. Moreover, this combined exposure influenced both glucose tolerance and insulin tolerance in mice, along with changing the expression of genes involved in lipid and glucose homeostasis . Specifically, the combined exposure to BPA and arsenic promoted the uptake of glucose and fatty acid from serum to liver, and genes involved in glycogenesis, glucogenesis, and fatty acid oxidation were activated in the liver in the combined exposure group. Taken together, these experimental results highlight the importance of considering the combined toxicity of environmental pollutants at levels relevant to human exposure, especially during the early life stages of mammals.

CAS / MDL: 7789-20-0
研究领域: 毒理学 · 代谢组学 · 环境健康科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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CELL · 2025 · IF 42.5

A microbial amino-acid-conjugated bile acid, tryptophan-cholic acid, improves glucose homeostasis via the orphan receptor MRGPRE

Jun Lin,Qixing Nie,Jie Cheng,Ya-Ni Zhong,Tianyao Zhang,Xiuying Zhang,Xiaoyan Ge,Yong Ding,Canyang Niu,Yuhua Gao,Kai Wang,Mingxin Gao,Xuemei Wang,Weixuan Chen,Chuyu Yun,Chuan Ye,Jinkun Xu,Weike Shaoyong,Lijun Zhang,Pan Shang,Xi Luo,Zhiwei Zhang,Xin Zheng,Xueying Sha,Jinxin Zhang,Shaoping Nie,Xuguang Zhang,Fazheng Ren,Huiying Liu,Erdan Dong,Xiao Yu,Linong Ji,Yanli Pang,Jin-Peng Sun,Changtao Jiang

Recently, microbial amino-acid-conjugated bile acids (MABAs) have been found to be prevalent in human samples. However, their physiological significance is still unclear. Here, we identify tryptophan-conjugated cholic acid (Trp-CA) as the most significantly decreased MABA in patients with type 2 diabetes (T2D), and its abundance is negatively correlated with clinical glycemic markers. We further demonstrate that Trp-CA improves glucose tolerance in diabetic mice. Mechanistically, we find that Trp-CA is a ligand of the orphan G protein-coupled receptor (GPCR) Mas-related G protein-coupled receptor family member E (MRGPRE) and determine the binding mode between the two. Both MRGPRE-Gs-cyclic AMP (cAMP) and MRGPRE-β-arrestin-1-aldolase A (ALDOA) signaling pathways contribute to the metabolic benefits of Trp-CA. Additionally, we find that the bacterial bile salt hydrolase/transferase of Bifidobacterium is responsible for the production of Trp-CA. Together, our findings pave the way for further research on MABAs and offer additional therapeutic targets for the treatment of T2D.

研究领域: 微生物学 · 代谢组学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ENVIRONMENTAL POLLUTION · 2018 · IF 4.358

Perinatal exposure to low-dose decabromodiphenyl ethane increased the risk of obesity in male mice offspring

Sen Yan,Dezhen Wang,Miaomiao Teng,Zhiyuan Meng,Jin Yan,Ruisheng Li,Ming Jia,Chenyang Yao,Jing Sheng,Sinuo Tian,Renke Zhang,Zhiqiang Zhou,Wentao Zhu

Decabromodiphenyl Ethane (DBDPE), a kind of new brominated flame retardants (NBFRs) used to replace DecaBDE, has been frequently detected in the environment and human samples. In this study, we explored its toxic effects on male mouse offspring after perinatal exposure to DBDPE. During the perinatal period, pregnant ICR mice were exposed to DBDPE (100 μg/kg body weight) via oral gavage. After weaning, male offspring were fed on a low-fat diet and a high-fat diet, respectively. We measured and recorded body weight, liver weight, and epididymis fat mass, blood biochemical markers, metabolites changes in liver, and gene expression involved in lipid and glucose homeostasis . The results showed that perinatal exposure to DBDPE increased the risk of obesity in mouse offspring and affected triglyceride synthesis, bile secretion, purine synthesis, mitochondrial function and glucose metabolism, furthermore, the use of HFD feeding may further exacerbate these effects. All of these results show that early-life exposure to low doses of DBDPE can promote the development of metabolic dysfunction, which in turn induces obesity.

CAS / MDL: 7789-20-0
研究领域: 环境科学 · 毒理学 · 代谢生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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FOOD AND CHEMICAL TOXICOLOGY · 2025 · IF 3.5

Titanium dioxide nanoparticles disturb glucose homeostasis in association with impaired enteroendocrine cell differentiation

Kai Zou,Linna Du,Jing Qin,Jiacheng Zhou,Yanping Xiao,Xixi Song,Hongxia Liu,Xiu Wang

Gut hormones secreted by enteroendocrine cells play a critical role in maintaining glucose homeostasis. However, the adverse endocrine effects related to glucose homeostasis caused by food additives are not well understood. This work aims to investigate the effects of titanium dioxide nanoparticles (TiO 2 NPs) in comparison to titanium dioxide microparticles (TiO 2 MPs) on glucose homeostasis, with a specific focus on the enteroendocrine cells and gut hormones. Our research found that exposure to 1% (w/w) TiO 2 NPs, unlike TiO 2 MPs, resulted in elevated blood glucose levels and impaired glucose tolerance in mice. Notably, 1% (w/w) TiO 2 NPs significantly influenced the differentiation of the intestinal epithelium while not causing any notable histological changes or affecting cell proliferation in the mouse ileum. Furthermore, the levels of gut hormones, including glucagon-like peptide-1 (GLP-1) , peptide YY (PYY) and cholecystokinin (CCK), released from mouse ileum tissues were also significantly reduced following exposure to 1% (w/w) TiO 2 NPs. Using the intestinal organoid model, we also discovered that 20 μg/mL TiO 2 NPs impaired enteroendocrine cell differentiation, reduced basal GLP-1 secretion levels, and disrupted the GLP-1 secretion response to nutrient stimuli. Our research highlights the detrimental effects of TiO 2 NPs as potential intestinal endocrine disruptor and underscores the need to optimize their particle size for safe use in the food industry.

CAS / MDL: 1317-70-0 13463-67-7
研究领域: 营养学 · 分子生物学 · 内分泌学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ACS Omega · 2018 · IF 0

Effect of γ-Aminobutyric Acid–Chitosan Nanoparticles on Glucose Homeostasis in Mice

Yuangang Liu,Weiji Weng,Shibin Wang,Ruimin Long,Hanwen Li,Huihui Li,Tengteng Li,Mengyi Wu

Diabetes mellitus is the most common endocrine disease worldwide; hyperglycemia is a hallmark of this disease. To alleviate the pain caused by diabetes, developing and utilizing effective diabetic drugs to maintain or recover the function of the residual β-cells is an attractive therapeutic approach. γ-aminobutyric acid (GABA) has been shown to have such effects, but it is easy to have reduced GABA activity under physiological conditions. In the present study, GABA–chitosan nanoparticles (GABA–CS NPs) were prepared, and glucose homeostasis, pancreatic β-cell protection, and anti-inflammatory effects of GABA–CS NPs were investigated in vivo. The results showed that blood glucose levels and IL-1β levels in the GABA–CS NP-administered group were both significantly lower, whereas the PDX1 expression was significantly higher than that of the impaired group (p < 0.01). This indicates that GABA–CS NPs can efficiently maintain glucose homeostasis, protect β-cells, and inhibit inflammation. These nanoparticles have the potential to be applied for future diabetes theranostics.

研究领域: 药理学 · 内分泌学 · 纳米技术 · 糖尿病研究
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EMBO JOURNAL · 2024 · IF 9.4

Intestinal NUCB2/nesfatin-1 regulates hepatic glucose production via the MC4R-cAMP-GLP-1 pathway

GengShan,YangShan,TangXuejiao,XueShiyao,LiKe,LiuDongfang,ChenChen,ZhuZhiming,ZhengHongting,WangYuanqiang,YangGangyi,LiLing,YangMengliu

Communication of gut hormones with the central nervous system is important to regulate systemic glucose homeostasis, but the precise underlying mechanism involved remain little understood. Nesfatin-1, encoded by nucleobindin-2 (NUCB2), a potent anorexigenic peptide hormone, was found to be released from the gastrointestinal tract, but its specific function in this context remains unclear. Herein, we found that gut nesfatin-1 can sense nutrients such as glucose and lipids and subsequently decreases hepatic glucose production. Nesfatin-1 infusion in the small intestine of NUCB2-knockout rats reduced hepatic glucose production via a gut – brain – liver circuit. Mechanistically, NUCB2/nesfatin-1 interacted directly with melanocortin 4 receptor (MC4R) through its H-F-R domain and increased cyclic adenosine monophosphate (cAMP) levels and glucagon-like peptide 1 (GLP-1) secretion in the intestinal epithelium, thus inhibiting hepatic glucose production. The intestinal nesfatin-1 -MC4R-cAMP-GLP-1 pathway and systemic gut-brain communication are required for nesfatin-1 - mediated regulation of liver energy metabolism. These findings reveal a novel mechanism of hepatic glucose production control by gut hormones through the central nervous system.

CAS / MDL: 133514-43-9
研究领域: 内分泌学 · 代谢学 · 胃肠病学 · 神经科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2019 · IF 3.571

Optimal Dietary Ferulic Acid for Suppressing the Obesity-Related Disorders in Leptin-Deficient Obese C57BL/6J-ob/ob Mice

Weiwei Wang,Yiou Pan,Li Wang,Hang Zhou,Ge Song,Yongwei Wang,Jianxue Liu,Aike Li

Ferulic acid (FA) is a major polyphenolic compound and has been shown to improve the glucose and lipid homeostasis in high-fat diet-induced obese mice. Here, we found the optimal level of dietary FA to ameliorate obesity and obesity-correlated disorders, and identified the responses of gut microbiota to dietary FA in genetic leptin-deficient obese (ob/ob) mice. The ob/ob mice exhibited persistent higher body weights, feed efficiency, white adipose tissue weights, and hepatic lipid accumulation, compared to those of the wild-type mice. However, 0.5% dietary FA suppressed these symptoms in ob/ob mice. The diversity of gut microbiota and the total abundance of obesity- and anti-obesity-related genera were not influenced after FA intervention in ob/ob mice. These data suggest that sufficient intake of FA (0.5%) could be useful for treating obesity or obesity-related diseases, and this weight-control effect is possibly not correlated with the gut–brain axis.

CAS / MDL: 64-18-6
研究领域: 营养学 · 微生物学 · 代谢学 · 药理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF APPLIED TOXICOLOGY · 2018 ·Vol. 38 ·期 6 ·810-823 · IF 2.909

Effect of titanium dioxide nanoparticles on glucose homeostasis after oral administration

Zhangjian Chen,Yun Wang,Xiang Wang,Lin Zhuo,Shi Chen,Shichuan Tang,Lin Zhao,Xianguo Luan,Guang Jia

As food additives, titanium dioxide nanoparticles (TiO 2 NPs) have been widely used in various products that are usually simultaneously consumed with a high content of sugar, thus necessitating research on the effect of TiO 2 NPs on glucose homeostasis. We conducted an animal study to explore the effect of orally administrated TiO 2 NPs on glucose absorption and metabolism in rats at 0, 2, 10 and 50 mg kg –1 body weight day –1 for 30 and 90 days. The results showed that oral exposure to TiO 2 NPs caused a slight and temporary hypoglycemic effect in rats at 30 days post-exposure but recovered at 90 days post-exposure. Decreased levels of intestinal glucose absorption and increased levels of hepatic glucose metabolism may be responsible for the hypoglycemic effect. Remodeling of the villi in the small intestine that decreased the surface area available for glucose absorption and increased levels of hepatic glucose uptake, utilization and storage related to hepatocellular injury are supposed to be the mechanisms. Our results demonstrated that dietary intake of TiO 2 NPs as food additives could affect the absorption and metabolism of glucose.

CAS / MDL: 13463-67-7
研究领域: 食品科学 · 毒理学 · 代谢
✓ 已验证 产品关联 DOI PubMed 高影响因子
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MOLECULES · 2023 ·Vol. 28 ·期 2 ·722 · IF 4.6

Effects of the Novel LaPLa-Enriched Medium- and Long-Chain Triacylglycerols on Body Weight, Glycolipid Metabolism, and Gut Microbiota Composition in High Fat Diet-Fed C57BL/6J Mice

Jinyuan Shi,Qianqian Wang,Chuang Li,Mengyu Yang,Muhammad Hussain,Junhui Zhang,Fengqin Feng,Hao Zhong

The roles of medium- and long-chain triacylglycerols (MLCT) on health benefits under high fat diet (HFD) conditions remain in dispute. This study was conducted to investigate the effects of novel LaPLa-rich MLCT on the glycolipid metabolism and gut microbiota in HFD-fed mice when pork fat is half replaced with MLCT and palm stearin (PS). The results showed that although MLCT could increase the body weight in the mouse model, it can improve the energy utilization, regulate the glucose and lipid metabolism, and inhibit the occurrence of inflammation. Furthermore, 16S rRNA gene sequencing of gut microbiota indicated that PS and MLCT affected the overall structure of the gut microbiota to a varying extent and specifically changed the abundance of some operational taxonomic units (OTUs). Moreover, several OTUs belonging to the generaDorea, Streptococcus, andg_Eryipelotrichaceaehad a high correlation with obesity and obesity-related metabolic disorders of the host. Therefore, it can be seen that this new MLCT has different properties and functions from the previous traditional MLCT, and it can better combine the advantages of MLCT, lauric acid, and sn-2 palmitate, as well as the advantages of health function and metabolism. In summary, this study explored the effects of LaPLa-enriched lipids on glycolipid metabolism in mice, providing theoretical support for future studies on the efficacy of different types of conjugated lipids, intending to apply them to industrial production and subsequent development of related products.Keywords:MLCT;lipid metabolism;glucose homeostasis;gut microbiota;inflammation

研究领域: 营养学 · 代谢学 · 微生物学 · 动物科学
✓ 已验证 DOI PubMed 高影响因子
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Nutrients · 2023 ·Vol. 15 ·期 4 ·980 · IF 5.9

Dietary Supplementation of Cedryl Acetate Ameliorates Adiposity and Improves Glucose Homeostasis in High-Fat Diet-Fed Mice

Jingya Guo,Mengjie Li,Yuhan Zhao,Seong-Gook Kang,Kunlun Huang,Tao Tong

Cedryl acetate (CA), also called acetyl cedrene, is approved by the FDA as a flavoring or adjuvant to be added to foods. In this study, we aimed to investigate the preventive benefits of CA on obesity and obesity-related metabolic syndrome caused by a high-fat diet (HFD). Three groups of C57BL/6J mice (ten-week-old) were fed Chow, an HFD, or an HFD with CA supplementation (100 mg/kg) for 19 weeks. We observed that CA supplementation significantly reduced weight gain induced by an HFD, decreased the weight of the visceral fat pads, and prevented adipocyte hypertrophy in mice. Moreover, mice in the CA group showed significant improvements in hepatic lipid accumulation, glucose intolerance, insulin resistance, and gluconeogenesis compared with the mice in the HFD group. Since 16S rRNA analysis revealed that the gut microbiota in the CA and HFD groups were of similar compositions at the phylum and family levels, CA may have limited effects on gut microbiota in HFD-fed mice. The beneficial effects on the metabolic parameters of CA were reflected by CA’s regulation of metabolism-related gene expression in the liver (includingPepck,G6Pase, andFbp1) and the epididymal white adipose tissues (includingPPARγ,C/EBPα,FABP4,FAS, Cytc,PGC-1α,PRDM16,Cidea, andCOX4) of the mice. In summary, a potent preventive effect of CA on HFD-induced obesity and related metabolic syndrome was highlighted by our results, and CA could be a promising dietary component for obesity intervention.Keywords:cedryl acetate;high-fat diet;obesity;gut microbiota

CAS / MDL: 10043-52-4
研究领域: 营养学 · 代谢学 · 药理学 · 微生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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MOLECULAR NUTRITION & FOOD RESEARCH · 2022 ·Vol. 66 ·期 10 ·2100772 · IF 6.575

Targeting Gut Microbiota and Host Metabolism with Dendrobium officinale Dietary Fiber to Prevent Obesity and Improve Glucose Homeostasis in Diet-Induced Obese Mice

Hong Zheng,Hui Ji,Kai Fan,Hangying Xu,Yinli Huang,Yafei Zheng,Qingqing Xu,Chen Li,Liangcai Zhao,Yuping Li,Hongchang Gao

Scope Obesity is becoming a major public health problem due to excess dietary fat intake. Dendrobium officinale ( D. officinale ) is a medicine food homology plant and exerts multiple health-promoting effects. However, its antiobesity effects and the potential mechanisms remain unclear. Methods and results High-fat diet (HFD)-fed mice are administered D. officinale dietary fiber (DODF) daily by gavage for 11 weeks. The results show that treatment with DODF alleviates obesity, liver steatosis, inflammation, and oxidant stress in HFD-induced obese mice. Improved glucose homeostasis in obese mice after DODF treatment is achieved by enhancing insulin pathway and hepatic glycogen synthesis. DODF restructures the gut microbiota in obese mice by decreasing the relative abundance of Bilophila and increasing the relative abundances of Akkermansia, Bifidobacterium , and Muribaculum . Also, DODF reshapes the metabolic phenotype of obese mice as indicated by up-regulating energy metabolism, increasing acetate and taurine, and reducing serum low density/very low density lipoproteins (LDL/VLDL). These beneficial effects are partly transferred by FMT, implying the gut microbiota as a target for the protective effect of DODF on obesity-related symptoms. Conclusion The results suggest that DODF can be used as a novel prebiotics to maintain the gut microbial homeostasis and improve metabolic health, preventing obesity and related metabolic syndrome.

CAS / MDL: 9012-54-8 9001-73-4
研究领域: 营养学 · 代谢学 · 微生物学 · 药理学 · 肥胖研究
✓ 已验证 产品关联 DOI PubMed 高影响因子
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