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FOOD AND CHEMICAL TOXICOLOGY · 2013 · IF 3.01

Pentamethylquercetin reduces fat deposition via Sirt1-mediated pathways in male obese mice induced by a high fat diet

Hua-Zong Ying,Jia-Na Zang,Li-Li Deng,Zhi-Yuan Wang,Chen-huan Yu

Pentamethylquercetin (PMQ) is a natural quercetin derivative found in a variety of edible herb. Although PMQ has potential as anti-diabetic agent, there have been no reports on its anti-adipogenic effects in the obese animals. This study investigated whether PMQ attenuates high-fat diet (HFD)-induced adipogenesis in the epididymal fat tissues of mice and explored its underlying mechanisms. In comparison with HFD-fed mice, mice fed with PMQ showed significantly lower body weight gain, adipose tissue mass, and plasma levels of triglyceride, total cholesterol, low-density lipoprotein cholesterol, and glucose, but higher plasma levels of high-density lipoprotein cholesterol. PMQ significantly reversed the HFD-induced regulation of Sirt1/mTOR signaling genes (Sirt1, mTOR , 4EBP1, and S6K1), and key adipogenic genes (PPARγ, SREBP1, FAS, ATGL, HSL, and Perilipin) in the epididymal adipose tissues of obese mice. However, nicotinamide appeared to partly inhibit PMQ-mediated anti-adipogenic effects involved in this attenuation. These results suggested that PMQ inhibited visceral adipogenesis by suppressing the Sirt1-mediated mTOR and adipogenesis signaling cascades. It might be a potential candidate for the treatment of obesity.

CAS / MDL: 98-92-0
研究领域: 药理学 · 营养学 · 分子生物学
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BIOCHEMICAL PHARMACOLOGY · 2017 · IF 4.581

Testosterone regulates 3T3-L1 pre-adipocyte differentiation and epididymal fat accumulation in mice through modulating macrophage polarization

Xiaojiao Ren,Xiaojian Fu,Xinhua Zhang,Shiqiang Chen,Shuguang Huang,Lun Yao,Guoquan Liu

Low testosterone levels are strongly related to obesity in males. The balance between the classically M1 and alternatively M2 polarized macrophages also plays a critical role in obesity. It is not clear whether testosterone regulates macrophage polarization and then affects adipocyte differentiation. In this report, we demonstrate that testosterone strengthens interleukin (IL) -4-induced M2 polarization and inhibits lipopolysaccharide (LPS)-induced M1 polarization, but has no direct effect on adipocyte differentiation. Cellular signaling studies indicate that testosterone regulates macrophage polarization through the inhibitory regulative G-protein (Gαi) mainly, rather than via androgen receptors , and phosphorylation of Akt. Moreover, testosterone inhibits pre-adipocyte differentiation induced by M1 macrophage medium. Lowering of serum testosterone in mice by injecting a luteinizing hormone receptor (LHR) peptide increases epididymal white adipose tissue. Testosterone supplementation reverses this effect. Therefore, our findings indicate that testosterone inhibits pre-adipocyte differentiation by switching macrophages to M2 polarization through the Gαi and Akt signaling pathways.

研究领域: 内分泌学 · 免疫学 · 细胞生物学 · 肥胖研究
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ACS Applied Materials & Interfaces · 2024 · IF 8.3

Hydrogel-Composited Laminate for Islet Immune-Isolation to Treat Type 1 Diabetes

Yi Wang,Kai Wang,Xi Wang,Ying Luo,Haifeng Chen

Challenges remain to be solved for the clinical translation of β-cell encapsulation technology in the treatment of type 1 diabetes (T1D). Successful delivery of β cells urgently needs the development of an encapsulation device with a thin dimension and rapid mass transport that offers stable immune isolation and complete retrieval. In this study, we focus on a laminate in which an islet-embedding alginate hydrogel layer (Alg) is sandwiched between two polymer layers (polyether sulfone, PES). Mechanical support by the PES layer protects the alginate from disintegrating after implantation and allows complete retrieval. The multilayered device has a thin membrane configuration (∼1 mm), and the edge of the laminate and the gaps between Alg and PES offer a semiopen structure that could be more permeable to molecules compared with the closed pocket of conventional macroencapsulation. Islets are suspended in the alginate solution and then encapsulated in the hydrogel layer in the middle of the laminate after gelation. Encapsulating syngeneic or xenogeneic islets in the laminate device corrected chemically induced T1D in mice for over 90 days in both the intraperitoneal space and the epididymal fat pad. The multilayered membrane system may therefore provide a translatable solution in β cell-transplantation therapy in T1D.

CAS / MDL: 39346-81-1
研究领域: 生物医学工程 · 糖尿病研究 · 组织工程 · 移植医学
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Food Bioscience · 2023 · IF 5.2

Tibetan highland barley fiber improves obesity and regulates gut microbiota in high-fat diet-fed mice

Linyao Gan,Jing Han,Chenyao Li,Jing Tang,Xuebing Wang,Yue Ma,Yefu Chen,Dongguang Xiao,Xuewu Guo

Tibetan highland barley fiber (T-Fiber) contains high dietary fiber (DF) and beta-glucose. Highland barley has been shown to reduce the risk of diseases associated with high-fat diets (HFD). In the present research, we studied whether T-Fiber could ameliorate HFD-induced obesity in mice and explored its regulatory effects on intestinal microbes . Our findings revealed that T-Fiber feeding significantly reduced weight gain and dyslipidemia , improved glucose tolerance and insulin resistance, alleviated chronic systemic inflammation, and increased short-chain fatty acids (SCFA) in feces in mice. Histological observations confirmed that T-Fiber alleviated Epididymal fat (EF) and lipid accumulation in the liver. In addition, 16s rRNA sequencing analysis of mice cecum contents showed that T-Fiber restored the HFD-induced gut microbiota. T-Fiber supplementation increased the abundance of potentially beneficial bacteria Muribaculaceae , Akkermansiaceae , and Lachnospiraceae_NK4A136_groups , while significantly reducing the abundance of Bacteroidaceae , Prevotellaceae , Rikenellaceae , and Alloprevotella . Furthermore, the increase in the production of SCFA may be related to the abundance of Lachnospiraceae_NK4A136_group . In conclusion, T-Fiber has some anti-obesity abilities under high-fat feeding and can be developed as a relevant anti-obesity product.

CAS / MDL: 64-19-7 107-92-6 79-09-4
研究领域: 营养学 · 微生物学 · 代谢学 · 肥胖研究 · 胃肠科学
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Food & Function · 2021 ·Vol. 12 ·期 8 ·3572-3585 · IF 5.396

Sargassum fusiforme fucoidan modifies gut microbiota and intestinal metabolites during alleviation of hyperglycemia in type 2 diabetic mice

Qifang Wu,Siya Wu,Yang Cheng,Zhongshan Zhang,Genxiang Mao,Shijun Li,Yue Yang,Xu Zhang,Mingjiang Wu,Haibin Tong

Type 2 diabetic mellitus (T2DM) is a complicated metabolic disorder that is now considered as a major global public health problem. Fucoidan exhibits diverse biological activities, especially prevention of metabolic diseases. In this regard, we herein aimed to reveal the beneficial effect of Sargassum fusiforme fucoidan (SFF) on high-fat diet (HFD) and streptozotocin (STZ) induced T2DM mice. We noted that on the one hand, SFF significantly decreased fasting blood glucose, diet and water intake, and hyperlipidemia, while on the other hand, it improved glucose tolerance. Furthermore, SFF reduced epididymal fat deposition, attenuated the pathological changes in heart and liver tissues, and decreased oxidative stress in diabetic mice. To explore the underlying mechanisms of these ameliorative effects, the gut microbiota was analyzed. Notably, SFF highly enriched benign microbes including Bacteroides, Faecalibacterium and Blautia, as well as increased levels of (R)-carnitine and choline in the colon of diabetic mice. This may be a potential mechanism for alleviating T2DM, thus implying the benefits of SFF as an adjuvant agent for T2DM treatment. Taken together, this study demonstrated a promising application of fucoidan as one of the adjuvant agents for the management of T2DM in the future.

CAS / MDL: 57-88-5 361-09-1
研究领域: 药理学 · 代谢学 · 微生物学 · 营养学 · 内分泌学
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2022 · IF 5.895

Preventive Effect of Apple Polyphenol Extract on High-Fat Diet-Induced Hepatic Steatosis in Mice through Alleviating Endoplasmic Reticulum Stress

Bei Yan,Lei Chen,Yanhui Wang,Jiacheng Zhang,Hui Zhao,Qinglian Hua,Shengjie Pei,Zihang Yue,Hui Liang,Huaqi Zhang

In this work, the protective effect of apple polyphenol extract (APE) on hepatic steatosis was investigated. Thirty-two C57BL/6J mice were assigned randomly to control group, hepatic steatosis group, lovastatin group, and APE group. After 8 weeks of intervention, APE supplementation markedly decreased the body weight gain, liver weight, liver index, epididymal adipose weight, epididymal adipose index, serum, and hepatic lipid levels. Hematoxylin and eosin staining revealed that APE supplementation alleviated histopathological changes of hepatic steatosis. Western blot revealed that APE downregulated the protein levels of GRP78, IRE1α, p-IRE1α, XBP1, PERK, p-PERK, p-eIF2α, ATF6, PPAR-γ, SREBP-1c, FAS, and ACC1. In conclusion, this study found that APE inhibited IRE1α-XBP1, PERK-eIF2α, and ATF6 signaling pathways to alleviate endoplasmic reticulum stress, thereby improving HFD-induced hepatic steatosis.

CAS / MDL: 75330-75-5
研究领域: 药理学 · 营养学 · 分子生物学 · 病理学
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FOOD RESEARCH INTERNATIONAL · 2021 · IF 6.475

Ethanol extract of Sargarsum fusiforme alleviates HFD/STZ-induced hyperglycemia in association with modulation of gut microbiota and intestinal metabolites in type 2 diabetic mice

Siya Wu,Jihui Zuo,Yang Cheng,Ya Zhang,Zhongshan Zhang,Mingjiang Wu,Yue Yang,Haibin Tong

Type 2 diabetes mellitus (T2DM) is considered a rapidly growing chronic disease that threatens human health worldwide. Extracts of various seaweeds have been shown to have anti-diabetic activity. Sargarsum fusiforme, an edible brown seaweed, has been shown to possess anti-inflammatory, anti-diabetic and anti-obesity activities. In this study, we investigated the beneficial effect of an ethanol extract of S. fusiforme (EE) on type 2 diabetes in mice induced with high-fat diet (HFD) and streptozotocin (STZ). Administering EE to the diabetic mice significantly reduced food intake, water intake and fasting blood glucose (FBG), while improving glucose tolerance, lipid profile and ameliorating hepatic oxidative stress. Furthermore, these animals also exhibited significantly diminished epididymal fat deposition, as well as less pathological changes in the heart and liver tissues, while displaying some highly enriched benign gut bacteria (e.g., Intestinimonas , Oscillibacter , Lachnoclostridium, unidentified_Lachnospiraceae , Roseburia and Anaerotruncus ) and a lower abundance of bacteria associated with diabetes or other metabolic diseases (e.g., Enterorhabdus and Romboutsia ). Metabolomic analysis revealed reduced levels of branched-chain amino acids (BCAA), such as l -valine and l -isoleucine, aromatic amino acids (AAA), such as l -tyrosine and l -phenylalanine, and increased levels of 4-hydroxyphenylacetic acid (4-HPA) in the gut content, suggesting that EE may impact T2DM through modulation of these compounds in the gut of the animals. Taken together, the results implied that S. fusiforme may contain valuable active components other than polysaccharides that have potential benefit in alleviating T2DM.

CAS / MDL: 57-88-5 361-09-1
研究领域: 药理学 · 营养学 · 糖尿病研究 · 微生物学 · 代谢组学
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