Evidence map›Paper›PMID 34074311›Full record

ArticleNutrition & metabolism2021

PS-341 alleviates chronic low-grade inflammation and improves insulin sensitivity through the inhibition of TM4 (UBAC2) degradation.

Lili Chen, Kuanping Ye, Xiaocheng Feng, Lianxi Li, Qin Li, Ying Huang, Xuanchun Wang, Rumei Li, Cheng Hu, Zhen Yang and 13 more

Abstract read
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In one paragraph

Article in Nutrition & metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

23 authors.

Lili Chen *Department of Endocrinology, Huashan Hospital Fudan University, 12 Middle Wulumuqi Road, Shanghai, 200040, China.
Kuanping Ye *Department of Endocrinology, Huashan Hospital Fudan University, 12 Middle Wulumuqi Road, Shanghai, 200040, China.
Xiaocheng Feng *Department of Endocrinology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Lianxi Li *Department of Endocrinology, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, China.
Qin Li *Department of Endocrinology, School of Medicine, Shanghai Ninth People's Hospital, Shanghai Jiaotong University, Shanghai, China.
Ying Huang *Department of Endocrinology, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai, China.
Xuanchun Wang *Department of Endocrinology, Huashan Hospital Fudan University, 12 Middle Wulumuqi Road, Shanghai, 200040, China.
Rumei Li *Department of Endocrinology, Huashan Hospital Fudan University, 12 Middle Wulumuqi Road, Shanghai, 200040, China.
Cheng Hu *Department of Endocrinology, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, China.
Zhen YangDepartment of Endocrinology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
Bin LuDepartment of Endocrinology, Huashan Hospital Fudan University, 12 Middle Wulumuqi Road, Shanghai, 200040, China.
Yehong YangDepartment of Endocrinology, Huashan Hospital Fudan University, 12 Middle Wulumuqi Road, Shanghai, 200040, China.
Jie WenDepartment of Endocrinology, Huashan Hospital Fudan University, 12 Middle Wulumuqi Road, Shanghai, 200040, China.
Zhaoyun ZhangDepartment of Endocrinology, Huashan Hospital Fudan University, 12 Middle Wulumuqi Road, Shanghai, 200040, China.
Min HeDepartment of Endocrinology, Huashan Hospital Fudan University, 12 Middle Wulumuqi Road, Shanghai, 200040, China.
Qinghua WangDepartment of Endocrinology, Huashan Hospital Fudan University, 12 Middle Wulumuqi Road, Shanghai, 200040, China.
Wenbai ZhouDepartment of Endocrinology, Huashan Hospital Fudan University, 12 Middle Wulumuqi Road, Shanghai, 200040, China.
Yintao LiDepartment of Chemotherapy, Shandong Tumor Hospital, Shandong University, Jinan, China.
Naijia LiuDepartment of Endocrinology, Huashan Hospital Fudan University, 12 Middle Wulumuqi Road, Shanghai, 200040, China.
Jinya HuangDepartment of Endocrinology, Huashan Hospital Fudan University, 12 Middle Wulumuqi Road, Shanghai, 200040, China.
Qiwei ShenDepartment of General Surgery, Huashan Hospital Fudan University, Shanghai, China.
Qiyuan YaoDepartment of General Surgery, Huashan Hospital Fudan University, Shanghai, China.
Renming HuDepartment of Endocrinology, Huashan Hospital Fudan University, 12 Middle Wulumuqi Road, Shanghai, 200040, China. renminghu@fudan.edu.cn.

Funding

National Natural Science Foundation of China 81030014, 81270902, 81471057
6 · The paper itself

Abstract

backgroundThe TM4 (UBAC2) protein, which contains 4 transmembrane domains and one ubiquitin binding domain, is mainly expressed in cell and nuclear membranes. The current research aimed to explore the role of TM4 in metabolic inflammation and to examine whether the ubiquitin-proteasome inhibitor PS-341 could regulate the function of TM4.

methodsThe metabolic phenotypes of TM4 knockout (KO) mice were studied. We next explored the association between the polymorphisms of TM4 and obesity in a Chinese Han population. TM4 expression in the visceral fat of obese patients who underwent laparoscopic cholecystectomy was also analysed. Finally, the effect of PS-341 on the degradation and function of the TM4 protein was investigated in vivo and in vitro.

resultsTM4 KO mice developed obesity, hepatosteatosis, hypertension, and glucose intolerance under a high-fat diet. TM4 counterregulated Nur77, IKKβ, and NF-kB both in vivo and in vitro. The TM4 SNP rs147851454 is significantly associated with obesity after adjusting for age and sex (OR 1.606, 95% CI 1.065-2.422 P = 0.023) in 3394 non-diabetic and 1862 type 2 diabetic adults of Han Chinese. TM4 was significantly downregulated in the visceral fat of obese patients. PS-341 induced TM4 expression through inhibition of TM4 degradation in vitro. In db/db mice, PS-341 administration led to downregulation of Nur77/IKKβ/NF-κB expression in visceral fat and liver, and alleviation of hyperglycaemia, hypertension, and glucose intolerance. The hyperinsulinaemic-euglycaemic clamp demonstrated that PS-341 improved the glucose infusion rate and alleviated insulin resistance in db/db mice.

conclusionsPS-341 alleviates chronic low-grade inflammation and improves insulin sensitivity through inhibition of TM4 degradation.

Indexed as

Insulin resistanceMetabolic inflammationObesityPS-341UBAC2

Identifiers

PMID34074311
PMCPMC8170790

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