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      SEIPIN: A Key Factor for Nuclear Lipid Droplet Generation and Lipid Homeostasis

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          Abstract

          Lipid homeostasis is essential for normal cell physiology. Generally, lipids are stored in a lipid droplet (LD), a ubiquitous organelle consisting of a neutral lipid core and a single layer of phospholipid membrane. It is thought that LDs are generated from the endoplasmic reticulum and then released into the cytosol. Recent studies indicate that LDs can exist in the nucleus, where they play an important role in the maintenance of cell phospholipid homeostasis. However, the details of nuclear lipid droplet (nLD) generation have not yet been clearly characterized. SEIPIN is a nonenzymatic protein encoded by the Berardinelli-Seip congenital lipodystrophy type 2 ( BSCL2) gene. It is associated with lipodystrophy diseases. Many recent studies have indicated that SEIPIN is essential for LDs generation. Here, we review much of this research in an attempt to explain the role of SEIPIN in nLD generation. From an integrative perspective, we conclude by proposing a theoretical model to explain how SEIPIN might participate in maintaining homeostasis of lipid metabolism.

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          Dynamics and functions of lipid droplets

          Lipid droplets are storage organelles at the centre of lipid and energy homeostasis. They have a unique architecture consisting of a hydrophobic core of neutral lipids, which is enclosed by a phospholipid monolayer that is decorated by a specific set of proteins. Originating from the endoplasmic reticulum, lipid droplets can associate with most other cellular organelles through membrane contact sites. It is becoming apparent that these contacts between lipid droplets and other organelles are highly dynamic and coupled to the cycles of lipid droplet expansion and shrinkage. Importantly, lipid droplet biogenesis and degradation, as well as their interactions with other organelles, are tightly coupled to cellular metabolism and are critical to buffer the levels of toxic lipid species. Thus, lipid droplets facilitate the coordination and communication between different organelles and act as vital hubs of cellular metabolism.
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            Tumor necrosis factor-alpha (TNF-alpha) has been shown to have certain catabolic effects on fat cells and whole animals. An induction of TNF-alpha messenger RNA expression was observed in adipose tissue from four different rodent models of obesity and diabetes. TNF-alpha protein was also elevated locally and systemically. Neutralization of TNF-alpha in obese fa/fa rats caused a significant increase in the peripheral uptake of glucose in response to insulin. These results indicate a role for TNF-alpha in obesity and particularly in the insulin resistance and diabetes that often accompany obesity.
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              In atherosclerosis, the accumulation of apolipoprotein B-lipoproteins in the matrix beneath the endothelial cell layer of blood vessels leads to the recruitment of monocytes, the cells of the immune system that give rise to macrophages and dendritic cells. Macrophages derived from these recruited monocytes participate in a maladaptive, nonresolving inflammatory response that expands the subendothelial layer due to the accumulation of cells, lipid, and matrix. Some lesions subsequently form a necrotic core, triggering acute thrombotic vascular disease, including myocardial infarction, stroke, and sudden cardiac death. This Review discusses the central roles of macrophages in each of these stages of disease pathogenesis. Copyright © 2011 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                02 November 2020
                November 2020
                : 21
                : 21
                : 8208
                Affiliations
                [1 ]Key Laboratory of Agriculture Animal Genetics, Breeding and Reproduction of the Ministry of Education & Key Laboratory of Swine Genetics and Breeding of the Ministry of Agriculture and Rural Affairs, College of Animal Science, Huazhong Agricultural University, Wuhan 430070, Hubei, China; hyj_1900@ 123456webmail.hzau.edu.cn (Y.J.); tanyanjie@ 123456webmail.hzau.edu.cn (Y.T.); pengxiang@ 123456webmail.hzau.edu.cn (P.Z.)
                [2 ]Bio-Medical Center of Huazhong Agricultural University, Wuhan 430070, Hubei, China
                [3 ]Institute of Biomedical Sciences, Key Laboratory of Animal Resistance Biology of Shandong Province, College of Life Sciences, Shandong Normal University, Jinan 250014, Shandong, China
                Author notes
                Author information
                https://orcid.org/0000-0002-4600-5312
                Article
                ijms-21-08208
                10.3390/ijms21218208
                7663086
                33147895
                aa510175-ab09-425c-ad8d-0916d0803255
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 21 September 2020
                : 28 October 2020
                Categories
                Review

                Molecular biology
                nuclear,lipid droplet,seipin,lipid homeostasis
                Molecular biology
                nuclear, lipid droplet, seipin, lipid homeostasis

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