title: TNF-α stimulates endothelial palmitic acid transcytosis and promotes insulin resistance.
abstract: Persistent elevation of plasma TNF-α is a marker of low grade systemic inflammation. Palmitic acid (PA) is the most abundant type of saturated fatty acid in human body. PA is bound with albumin in plasma and could not pass through endothelial barrier freely. Albumin-bound PA has to be transported across monolayer endothelial cells through intracellular transcytosis, but not intercellular diffusion. In the present study, we discovered that TNF-α might stimulate PA transcytosis across cardiac microvascular endothelial cells, which further impaired the insulin-stimulated glucose uptake by cardiomyocytes and promoted insulin resistance. In this process, TNF-α-stimulated endothelial autophagy and NF-κB signaling crosstalk with each other and orchestrate the whole event, ultimately result in increased expression of fatty acid transporter protein 4 (FATP4) in endothelial cells and mediate the increased PA transcytosis across microvascular endothelial cells. Hopefully the present study discovered a novel missing link between low grade systemic inflammation and insulin resistance.
authors.affiliation: Department of endocrinology, Institute of geriatric medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and technology, 430077, Wuhan, Hubei, China.|Department of Pharmacology, School of basic medicine, Tongji Medical College, Huazhong University of Science and technology, 430030, Wuhan, Hubei, China.|Hubei Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, Tongji Medical College, Huazhong University of Science and technology, 430030, Wuhan, Hubei, China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of endocrinology, Institute of geriatric medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and technology, 430077, Wuhan, Hubei, China.|Department of Pharmacology, School of basic medicine, Tongji Medical College, Huazhong University of Science and technology, 430030, Wuhan, Hubei, China.|Hubei Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, Tongji Medical College, Huazhong University of Science and technology, 430030, Wuhan, Hubei, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, School of basic medicine, Tongji Medical College, Huazhong University of Science and technology, 430030, Wuhan, Hubei, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zheng
authors.affiliation: Department of Pharmacology, School of basic medicine, Tongji Medical College, Huazhong University of Science and technology, 430030, Wuhan, Hubei, China.
authors.forename: Shasha
authors.initials: S
authors.lastname: Xing
authors.affiliation: Department of Pharmacology, School of basic medicine, Tongji Medical College, Huazhong University of Science and technology, 430030, Wuhan, Hubei, China.
authors.forename: Yaogong
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, School of basic medicine, Tongji Medical College, Huazhong University of Science and technology, 430030, Wuhan, Hubei, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Bian
authors.affiliation: Department of Pharmacology, School of basic medicine, Tongji Medical College, Huazhong University of Science and technology, 430030, Wuhan, Hubei, China.
authors.forename: Guangjie
authors.initials: G
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, School of basic medicine, Tongji Medical College, Huazhong University of Science and technology, 430030, Wuhan, Hubei, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pharmacology, School of basic medicine, Tongji Medical College, Huazhong University of Science and technology, 430030, Wuhan, Hubei, China.
authors.forename: Juyi
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of endocrinology, Institute of geriatric medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and technology, 430077, Wuhan, Hubei, China.
authors.forename: Xiangli
authors.initials: X
authors.lastname: Bai
authors.affiliation: Department of Pharmacology, School of basic medicine, Tongji Medical College, Huazhong University of Science and technology, 430030, Wuhan, Hubei, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of endocrinology, Institute of geriatric medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and technology, 430077, Wuhan, Hubei, China.
authors.forename: Xiong
authors.initials: X
authors.lastname: Jia
authors.affiliation: Department of Pharmacology, School of basic medicine, Tongji Medical College, Huazhong University of Science and technology, 430030, Wuhan, Hubei, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of endocrinology, Institute of geriatric medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and technology, 430077, Wuhan, Hubei, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of endocrinology, Institute of geriatric medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and technology, 430077, Wuhan, Hubei, China.|Department of Pharmacology, School of basic medicine, Tongji Medical College, Huazhong University of Science and technology, 430030, Wuhan, Hubei, China.|Hubei Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, Tongji Medical College, Huazhong University of Science and technology, 430030, Wuhan, Hubei, China.
authors.forename: Si
authors.initials: S
authors.lastname: Jin
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D050612:Fatty Acid Transport Proteins / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D055806:Microvessels / Q000473:pathology; D008954:Models, Biological; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D019308:Palmitic Acid / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D057900:Transcytosis / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D050612:Fatty Acid Transport Proteins; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; C493572:Slc27a4 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D019308:Palmitic Acid; D011493:Protein Kinase C