論文 - 大﨑　雄樹

Distinct features of two lipid droplets types in cell nuclei from patients with liver diseases

Norihiro Imai, Yuki Ohsaki, Jinglei Cheng, Jingjing Zhang, Fumitaka Mizuno, Taku Tanaka, Shinya Yokoyama, Kenta Yamamoto, Takanori Ito, Yoji Ishizu, Takashi Honda, Masatoshi Ishigami, Hiroaki Wake, Hiroki Kawashima

Scientific Reports ( Springer Science and Business Media LLC )  13 ( 1 )  2023年04月

担当区分：   筆頭著者  , 責任著者

　概要を見る

Abstract Lipid droplets (LDs) have been observed in the nuclei of hepatocytes; however, their significance in liver disease remains unresolved. Our purpose was to explore the pathophysiological features of intranuclear LDs in liver diseases. We included 80 patients who underwent liver biopsies; the specimens were dissected and fixed for electron microscopy analysis. Depending on the presence of adjacent cytoplasmic invagination of the nuclear membrane, LDs in the nuclei were classified into two types: nucleoplasmic LDs (nLDs) and cytoplasmic LD invagination with nucleoplasmic reticulum (cLDs in NR). nLDs were found in 69% liver samples and cLDs in NR were found in 32%; no correlation was observed between the frequencies of the two LD types. nLDs were frequently found in hepatocytes of patients with nonalcoholic steatohepatitis, whereas cLDs in NR were absent from the livers of such patients. Further, cLDs in NR were often found in hepatocytes of patients with lower plasma cholesterol level. This indicates that nLDs do not directly reflect cytoplasmic lipid accumulation and that formation of cLDs in NR is inversely correlated to the secretion of very low-density lipoproteins. Positive correlations were found between the frequencies of nLDs and endoplasmic reticulum (ER) luminal expansion, suggesting that nLDs are formed in the nucleus upon ER stress. This study unveiled the presence of two distinct nuclear LDs in various liver diseases.

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Oleic acid‐bound <scp>FABP7</scp> drives glioma cell proliferation through regulation of nuclear lipid droplet formation

Banlanjo Abdulaziz Umaru, Yoshiteru Kagawa, Yuki Ohsaki, Yijun Pan, Chuck T. Chen, Daniel K. Chen, Toshiaki Abe, Subrata Kumar Shil, Hirofumi Miyazaki, Shuhei Kobayashi, Motoko Maekawa, Yui Yamamoto, Tunyanat Wannakul, Shuhan Yang, Richard P. Bazinet, Yuji Owada

The FEBS Journal ( Wiley )  290 ( 7 ) 1798 - 1821  2022年11月

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Oxygen-Glucose Deprivation Decreases the Motility and Length of Axonal Mitochondria in Cultured Dorsal Root Ganglion Cells of Rats.

Shin Kikuchi, Takayuki Kohno, Takashi Kojima, Haruyuki Tatsumi, Yuki Ohsaki, Takafumi Ninomiya

Cellular and molecular neurobiology    2022年06月  [国際誌]

　概要を見る

Controlling axonal mitochondria is important for maintaining normal function of the neural network. Oxygen-glucose deprivation (OGD), a model used for mimicking ischemia, eventually induces neuronal cell death similar to axonal degeneration. Axonal mitochondria are disrupted during OGD-induced neural degeneration; however, the mechanism underlying mitochondrial dysfunction has not been completely understood. We focused on the dynamics of mitochondria in axons exposed to OGD; we observed that the number of motile mitochondria significantly reduced in 1 h following OGD exposure. In our observation, the decreased length of stationary mitochondria was affected by the following factors: first, the halt of motile mitochondria; second, the fission of longer stationary mitochondria; and third, a transformation from tubular to spherical shape in OGD-exposed axons. Motile mitochondria reduction preceded stationary mitochondria fragmentation in OGD exposure; these conditions induced the decrease of stationary mitochondria in three different ways. Our results suggest that mitochondrial morphological changes precede the axonal degeneration while ischemia-induced neurodegeneration.

DOI PubMed

Nuclear lipid droplets form in the inner nuclear membrane in a seipin-independent manner.

Kamil Sołtysik, Yuki Ohsaki, Tsuyako Tatematsu, Jinglei Cheng, Asami Maeda, Shin-Ya Morita, Toyoshi Fujimoto

The Journal of cell biology   220 ( 1 )  2021年01月  [査読有り]  [国際誌]

　概要を見る

Nuclear lipid droplets (LDs) in hepatocytes are derived from precursors of very-low-density lipoprotein in the ER lumen, but it is not known how cells lacking the lipoprotein secretory function form nuclear LDs. Here, we show that the inner nuclear membrane (INM) of U2OS cells harbors triglyceride synthesis enzymes, including ACSL3, AGPAT2, GPAT3/GPAT4, and DGAT1/DGAT2, and generates nuclear LDs in situ. mTOR inhibition increases nuclear LDs by inducing the nuclear translocation of lipin-1 phosphatidic acid (PA) phosphatase. Seipin, a protein essential for normal cytoplasmic LD formation in the ER, is absent in the INM. Knockdown of seipin increases nuclear LDs and PA in the nucleus, whereas seipin overexpression decreases these. Seipin knockdown also up-regulates lipin-1β expression, and lipin-1 knockdown decreases the effect of seipin knockdown on nuclear LDs without affecting PA redistribution. These results indicate that seipin is not directly involved in nuclear LD formation but instead restrains it by affecting lipin-1 expression and intracellular PA distribution.

DOI PubMed

Long-term autophagy is sustained by activation of CCTβ3 on lipid droplets.

Yuta Ogasawara, Jinglei Cheng, Tsuyako Tatematsu, Misaki Uchida, Omi Murase, Shogo Yoshikawa, Yuki Ohsaki, Toyoshi Fujimoto

Nature communications   11 ( 1 ) 4480 - 4480  2020年09月  [査読有り]  [国際誌]

　概要を見る

Macroautophagy initiates by formation of isolation membranes, but the source of phospholipids for the membrane biogenesis remains elusive. Here, we show that autophagic membranes incorporate newly synthesized phosphatidylcholine, and that CTP:phosphocholine cytidylyltransferase β3 (CCTβ3), an isoform of the rate-limiting enzyme in the Kennedy pathway, plays an essential role. In starved mouse embryo fibroblasts, CCTβ3 is initially recruited to autophagic membranes, but upon prolonged starvation, it concentrates on lipid droplets that are generated from autophagic degradation products. Omegasomes and isolation membranes emanate from around those lipid droplets. Autophagy in prolonged starvation is suppressed by knockdown of CCTβ3 and is enhanced by its overexpression. This CCTβ3-dependent mechanism is also present in U2OS, an osteosarcoma cell line, and autophagy and cell survival in starvation are decreased by CCTβ3 depletion. The results demonstrate that phosphatidylcholine synthesis through CCTβ3 activation on lipid droplets is crucial for sustaining autophagy and long-term cell survival.

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Intracellular Organelles Driven by Liquid-Liquid Phase Separation

Shunsuke F. SHIMOBAYASHI, Yuki OHSAKI

Seibutsu Butsuri ( Biophysical Society of Japan )  60 ( 5 ) 267 - 271  2020年

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Universal phase behaviors of intracellular lipid droplets.

Shunsuke F Shimobayashi, Yuki Ohsaki

Proceedings of the National Academy of Sciences of the United States of America   116 ( 51 ) 25440 - 25445  2019年12月  [査読有り]  [国際誌]

　概要を見る

Lipid droplets are cytoplasmic microscale organelles involved in energy homeostasis and handling of cellular lipids and proteins. The core structure is mainly composed of two kinds of neutral lipids, triglycerides and cholesteryl esters, which are coated by a phospholipid monolayer and proteins. Despite the liquid crystalline nature of cholesteryl esters, the connection between the lipid composition and physical states is poorly understood. Here, we present a universal intracellular phase diagram of lipid droplets, semiquantitatively consistent with the in vitro phase diagram, and reveal that cholesterol esters cause the liquid-liquid crystal phase transition under near-physiological conditions. We moreover combine in vivo and in vitro studies, together with the theory of confined liquid crystals, to suggest that the radial molecular alignments in the liquid crystallized lipid droplets are caused by an anchoring force at the droplet surface. Our findings on the phase transition of lipid droplets and resulting molecular organization contribute to a better understanding of their biological functions and diseases.

DOI PubMed

Nuclear lipid droplets derive from a lipoprotein precursor and regulate phosphatidylcholine synthesis

Kamil So{\l}tysik, Yuki Ohsaki, Tsuyako Tatematsu, Jinglei Cheng, Toyoshi Fujimoto

Nature Communications ( Springer Nature )  10 ( 1 ) 1230 - 1230  2019年12月  [査読有り]  [国際誌]

担当区分：   筆頭著者  , 責任著者

　概要を見る

The original version of this Article contained errors in the Abstract and Introduction, whereby CCTα was incorrectly defined as an abbreviation of CDP-choline diacylglycerol phosphotransferase α, instead of CTP:phosphocholine cytidylyltransferase α. This has now been corrected in both the PDF and HTML versions of the Article.

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Nuclear lipid droplets derive from a lipoprotein precursor and regulate phosphatidylcholine synthesis.

Kamil Sołtysik, Yuki Ohsaki, Tsuyako Tatematsu, Jinglei Cheng, Toyoshi Fujimoto

Nature communications   10 ( 1 ) 473 - 473  2019年01月  [国際誌]

　概要を見る

The origin and physiological significance of lipid droplets (LDs) in the nucleus is not clear. Here we show that nuclear LDs in hepatocytes are derived from apolipoprotein B (ApoB)-free lumenal LDs, a precursor to very low-density lipoproprotein (VLDL) generated in the ER lumen by microsomal triglyceride transfer protein. ApoB-free lumenal LDs accumulate under ER stress, grow within the lumen of the type I nucleoplasmic reticulum, and turn into nucleoplasmic LDs by disintegration of the surrounding inner nuclear membrane. Oleic acid with or without tunicamycin significantly increases the formation of nucleoplasmic LDs, to which CDP-choline diacylglycerol phosphotransferase α (CCTα) is recruited, resulting in activation of phosphatidylcholine (PC) synthesis. Perilipin-3 competes with CCTα in binding to nucleoplasmic LDs, and thus, knockdown and overexpression of perilipin-3 increases and decreases PC synthesis, respectively. The results indicate that nucleoplasmic LDs in hepatocytes constitute a feedback mechanism to regulate PC synthesis in accordance with ER stress.

DOI PubMed

Duo in a Mystical Realm—Nuclear Lipid Droplets and the Inner Nuclear Membrane

Kamil Sołtysik, Yuki Ohsaki, Toyoshi Fujimoto

Contact ( SAGE Publications )  2   251525641989696 - 251525641989696  2019年01月  [査読有り]  [招待有り]

　概要を見る

The lipid droplet (LD) is a cytoplasmic organelle, but it also exists in the nucleus under some conditions or in some cell types. New studies have revealed that nuclear LDs do not occur by haphazard entry of cytoplasmic LDs. Instead, they are generated by specific mechanisms that are increasingly understood. The inner nuclear membrane (INM) plays a critical role in nuclear LD formation in both mammalian hepatocytes and budding yeast, although in significantly different ways. Hepatocyte nuclear LDs derive from precursors of very low-density lipoprotein lacking apolipoprotein B-100, which form in the endoplasmic reticulum lumen and accumulate in intranuclear extensions of the perinuclear space called type I nucleoplasmic reticulum. In contrast, nuclear LDs in yeast are generated by triglyceride synthesized in the INM. Nuclear LDs in hepatocytes and budding yeast are both instrumental in the regulation of phospholipid synthesis; however, again they function in different ways. As the full functional importance is as yet unknown, the close relationship of nuclear LDs and the INM is an attractive target of research from both physiological and pathological perspectives.

DOI

Linkage between lipid droplet formation and nuclear deformation in HeLa human cervical cancer cells

Takir Gizem Gulevin, Ohsaki Yuki, Morotomi-Yano Keiko, Yano Ken-ichi, Saitoh Hisato

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   504 ( 2 ) 485-490 - 490  2018年10月  [査読有り]  [国際誌]

　概要を見る

Because lipid droplets (LDs) and the nucleus are cellular organelles that regulate seemingly very different biochemical processes, very little attention has been focused on their possible interplay. Here, we report a correlation between nuclear morphology and cytoplasmic LD formation in HeLa human cervical cells. When the cells were treated with oleic acid (OA), LDs were formed in the cytoplasm, but not in the nucleoplasm. Interestingly, cells harboring OA-induced cytoplasmic LDs showed deformity of the nucleus, particularly at the nuclear rim. Conversely, when alteration from a single spherical nuclear shape to a multinucleated form was enforced by coadministration of paclitaxel and reversine, a significant amount of LDs was detected in the cytoplasm of the multinucleated cells. These two distinct pharmacological culture conditions not only allow analysis of the previously underappreciated organelle relationship, but also provide insights into the mutual affectability of LD formation and nuclear deformation.

DOI PubMed

Syntaxin 17 promotes lipid droplet formation by regulating the distribution of acyl-CoA synthetase 3

Hana Kimura, Kohei Arasaki, Yuki Ohsaki, Toyoshi Fujimoto, Takayuki Ohtomo, Junji Yamada, Mitsuo Tagaya

Journal of Lipid Research ( American Society for Biochemistry and Molecular Biology Inc. )  59 ( 5 ) 805 - 819  2018年  [査読有り]  [国際誌]

　概要を見る

Lipid droplets (LDs) are ubiquitous organelles that contain neutral lipids and are surrounded by a phospholipid monolayer. How proteins specifically localize to the phospholipid monolayer of the LD surface has been a matter of extensive investigations. In the present study, we show that syntaxin 17 (Stx17), a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein whose expression in the liver is regulated by diet, participates in LD biogenesis by regulating the distribution of acyl-CoA synthetase (ACSL)3, a key enzyme for LD biogenesis that redistributes from the endoplasmic reticulum (ER) to LDs during LD formation. Stx17 interacts with ACSL3, but not with LD formation-unrelated ACSL1 or ACSL4, through its SNARE domain. The interaction occurs at the ER-mitochondria interface and depends on the active site occupancy of ACSL3. Depletion of Stx17 impairs ACSL3 redistribution to nascent LDs. The defect in LD maturation due to Stx17 knockdown can be compensated for by ACSL3 overexpression, suggesting that Stx17 increases the efficiency of ACSL3 redistribution to LDs. Moreover, we show that the interaction between Stx17 and ACSL3 during LD maturation may be regulated by synaptosomal-associated protein of 23 kDa.

DOI PubMed

The lipid droplet and the endoplasmic reticulum

Yuki Ohsaki, Kamil Sołtysik, Toyoshi Fujimoto

Advances in Experimental Medicine and Biology ( Springer New York LLC )  997   111 - 120  2017年  [招待有り]  [国際誌]

担当区分：   筆頭著者

　概要を見る

Lipid droplets (LDs) are often found adjacent to the endoplasmic reticulum (ER). The ER–LD association may appear morphologically similar to the prototypical membrane contact sites found between the ER and other organelles, but the functional relationship between the ER and LDs is unique in that highly hydrophobic lipid esters are transported between them. This transportation is thought to occur through some form of membrane continuity, but its details are yet to be defined. Lipin, seipin, and FIT proteins, which are located at the ER–LD interface, may be involved in the lipid ester transport and probably play important roles for functional connectivity of the two organelles. More recently, LDs in the nucleus were found to be closely adhered to the inner nuclear membrane, representing a specialized form of the ER–LD association. In this article, we will give an overview of the ER–LD association, which is still filled with many unanswered questions.

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A New Electron Microscopic Method to Observe the Distribution of Phosphatidylinositol 3,4-bisphosphate

Sharmin Aktar, Sho Takatori, Takuma Tsuji, Minami Orii, Yuki Ohsaki, Jinglei Cheng, Toyoshi Fujimoto

ACTA HISTOCHEMICA ET CYTOCHEMICA ( JAPAN SOC HISTOCHEMISTRY & CYTOCHEMISTRY )  50 ( 5 ) 141 - 147  2017年  [査読有り]  [国内誌]

　概要を見る

Phosphatidylinositol 3,4-bisphosphate [PtdIns(3,4) P-2] is a phosphoinositide that plays important roles in signal transduction, endocytosis, and cell migration among others. The intracellular distribution of PtdIns(3,4) P-2 has mainly been studied by observing the distribution of GFP-tagged PtdIns(3,4) P-2-binding protein domains in live cells and by labeling with anti-PtdIns(3,4) P-2 antibody in fixed cell samples, but these methods only offer low spatial resolution results and may have pitfalls. In the present study, we developed an electron microscopic method to observe the PtdIns(3,4) P-2 distribution using the SDS-treated freeze-fracture replica labeling method. The recombinant GST-tagged pleckstrin homology (PH) domain of TAPP1 was used as the binding probe, and its binding to PtdIns(3,4) P-2 in the freeze-fracture replica was confirmed by using liposomes containing different phosphoinositides and by the lack of labeling by a mutant probe, in which one amino acid in the PH domain was substituted. The method was applied to NIH3T3 cell samples and showed that the increase of PtdIns(3,4) P-2 in cells treated with hydrogen peroxide occurs in the cytoplasmic leaflet of the plasma membrane, except in the caveolar membrane. The present method can define the distribution of PtdIns(3,4) P-2 at a high spatial resolution and will facilitate our understanding of the physiological function of this less studied phosphoinositide.

DOI PubMed

PML isoform II plays a critical role in nuclear lipid droplet formation

Yuki Ohsaki, Takeshi Kawai, Yukichika Yoshikawa, Jinglei Cheng, Eija Jokitalo, Toyoshi Fujimoto

JOURNAL OF CELL BIOLOGY ( ROCKEFELLER UNIV PRESS )  212 ( 1 ) 29 - 38  2016年01月  [査読有り]  [国際誌]

担当区分：   筆頭著者

　概要を見る

Lipid droplets (LDs) in the nucleus of hepatocyte-derived cell lines were found to be associated with premyelocytic leukemia (PML) nuclear bodies (NBs) and type I nucleoplasmic reticulum (NR) or the extension of the inner nuclear membrane. Knockdown of PML isoform II (PML-II) caused a significant decrease in both nuclear LDs and type I NR, whereas overexpression of PML-II increased both. Notably, these effects were evident only in limited types of cells, in which a moderate number of nuclear LDs exist intrinsically, and PML-II was targeted not only at PML NBs, but also at the nuclear envelope, excluding lamins and SUN proteins. Knockdown of SUN proteins induced a significant increase in the type I NR and nuclear LDs, but these effects were cancelled by simultaneous knockdown of PML-II. Nuclear LDs harbored diacylglycerol O-acyltransferase 2 and CTP : phosphocholine cytidylyltransferase a and incorporated newly synthesized lipid esters. These results corroborated that PML-II plays a critical role in generating nuclear LDs in specific cell types.

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電子顕微鏡による脂肪滴と膜脂質の探索

藤本豊士, 大崎雄樹, 辻琢磨

Proceedings of Clinical Electron Microscopy   35   1‐3  2016年

J-GLOBAL

Inhibition of Niemann-Pick-Type C1-Like1 by Ezetimibe Activates Autophagy in Human Hepatocytes and Reduces Mutant alpha 1-Antitrypsin Z Deposition

Takeshi Yamamura, Yuki Ohsaki, Michitaka Suzuki, Yuki Shinohara, Tsuyako Tatematsu, Jinglei Cheng, Masato Okada, Naoki Ohmiya, Yoshiki Hirooka, Hidemi Goto, Toyoshi Fujimoto

HEPATOLOGY ( WILEY-BLACKWELL )  59 ( 4 ) 1591 - 1599  2014年04月  [査読有り]  [国際誌]

　概要を見る

Autophagy can degrade aggregate-prone proteins, but excessive autophagy can have adverse effects. It would be beneficial if autophagy could be enhanced in a cell type-specific manner, but this has been difficult because the basic mechanism of autophagy is common. In the present study we found that inhibition of Niemann-Pick-type C1-like 1 (NPC1L1) by ezetimibe activates autophagy only in hepatocytes and small intestinal epithelia, but not in other cells. Ezetimibe induced accumulation of free cholesterol in the late endosome/lysosome and increased partitioning of a Ragulator component, LAMTOR1, in rafts. The latter change led to down-regulation of mammalian target of rapamycin (mTOR)C1 activity by decreasing mTOR recruitment to the late endosome/lysosome and activated autophagy. A primary effect of ezetimibe was found to be a decrease of free cholesterol in the plasma membrane, because all the results caused by ezetimibe were suppressed by supplementation of cholesterol as a methyl-beta-cyclodextrin complex. By enhancing autophagy in human primary hepatocytes with ezetimibe, insoluble mutant alpha 1-antitrypsin Z was reduced significantly. Conclusion: Inhibition of NPC1L1 by ezetimibe activates autophagy in human hepatocytes by modulating cholesterol homeostasis. Ezetimibe may be used to ameliorate liver degeneration in alpha 1-antitrypsin deficiency. (Hepatology 2014;59:1591-1599)

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Open Questions in Lipid Droplet Biology

Yuki Ohsaki, Michitaka Suzuki, Toyoshi Fujimoto

CHEMISTRY & BIOLOGY ( CELL PRESS )  21 ( 1 ) 86 - 96  2014年01月  [査読有り]  [招待有り]  [国際誌]

担当区分：   筆頭著者

　概要を見る

Lipid droplets (LDs) have been the focus of intense research for the past decade because of their active engagement in lipid metabolism and relationship with diseases. In contrast to other intracellular organelles, LDs are composed of a mass of hydrophobic lipid esters that is covered with a phospholipid monolayer. The unique architecture makes the LD a formidable object to study by the methods available today, and many fundamental questions remain unanswered. This review focuses on some of those questions, such as how LDs form and grow, how proteins move to and from LDs, and how LDs are related to protein degradation; we will also discuss what is not known about LDs. We think that small LDs that have thus far eluded analysis are the key to resolving many of the above-mentioned questions.

DOI PubMed

Inhibition of ADP-ribosylation suppresses aberrant accumulation of lipidated apolipoprotein B in the endoplasmic reticulum

Yuki Ohsaki, Jinglei Cheng, Kazushi Yamairi, Xiaoyue Pan, M. Mahmood Hussain, Toyoshi Fujimoto

FEBS LETTERS ( ELSEVIER SCIENCE BV )  587 ( 22 ) 3696 - 3702  2013年11月  [査読有り]  [国際誌]

担当区分：   筆頭著者

　概要を見る

ApoB-crescent, an endoplasmic reticulum (ER)-lipid droplet amalgamation structure, is a useful marker to indicate aberrant lipidated apolipoprotein B accumulation in the hepatocyte ER. Blockade of the ER-to-Golgi transport by either vesicle transport inhibitors or dominant-negative Arf1 caused a significant increase in ApoB-crescents. However, a low concentration of Brefeldin A induced the same result without affecting protein secretion, suggesting ADP-ribosylation as an additional mechanism. ADP-ribosylation inhibitors not only suppressed the increase of ApoB-crescents, but also rapidly dissolved existing ApoB-crescents. These results implicate the involvement of ADP-ribosylation in the ApoB-crescent formation and maintenance process at the ER. (C) 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

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Alleviation of seipinopathy-related ER stress by triglyceride storage.

Maarit Hölttä-Vuori, Veijo T Salo, Yuki Ohsaki, Maximiliano L Suster, Elina Ikonen

Human molecular genetics   22 ( 6 ) 1157 - 66  2013年03月  [国際誌]

　概要を見る

Mutations affecting the N-glycosylation site in Berardinelli-Seip lipodystrophy (BSCL)-associated gene BSCL2/seipin lead to a dominantly inherited spastic paraplegia termed seipinopathy. While the loss of function of seipin leads to severe congenital lipodystrophy, the effects of seipin N-glycosylation mutations on lipid balance in the nervous system are unknown. In this study, we show that expression of seipin N-glycosylation mutant N88S led to decreased triglyceride (TG) content in astrocytoma and motor neuron cell lines. This was corrected by supplementation with exogenous oleic acid. Upon oleic acid loading, seipin N88S protein was relocated from the endoplasmic reticulum (ER) to the surface of lipid droplets and this was paralleled by alleviation of ER stress induced by the mutant protein. This effect was not limited to seipin N88S, as oleic acid loading also reduced tunicamycin-induced ER stress in motor neuron cells. Furthermore, both seipin N88S and tunicamycin-induced ER stress were decreased by inhibiting lipolysis, suggesting that lipid droplets protected neuronal cells from ER stress. In developing zebrafish larvae, seipin N88S expression led to TG imbalance and reduced spontaneous free swimming. Importantly, supplementation with exogenous oleic acid reduced ER stress in the zebrafish head and increased fish motility. We propose that the decreased TG content contributes to the pathology induced by seipin N88S, and that rescuing TG levels may provide a novel therapeutic strategy in seipinopathy.

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