Details of a Researcher - OOSAKI Yuuki

Papers - OOSAKI Yuuki

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Pathological significance of intranuclear structures in liver biopsy samples.

Norihiro Imai, Yuki Ohsaki, Jinglei Cheng, Hanna Kawecka, Jingjing Zhang, Fumitaka Mizuno, Taku Tanaka, Shinya Yokoyama, Kenta Yamamoto, Takanori Ito, Yoji Ishizu, Takashi Honda, Tetsuya Ishikawa, Michał Woźniak, Hiroaki Wake, Hiroki Kawashima

Hepatology research : the official journal of the Japan Society of Hepatology 55 ( 7 ) 1065 - 1074 2025.07 [International journal]

AIM: Glycogenated nuclei (GN) are glycogen deposits within the nuclei and are a frequent pathological finding in metabolic dysfunction-associated steatotic liver disease. This study aimed to investigate the relationship between GN and two morphologically distinct types of intranuclear lipid droplets in liver biopsy specimens and to explore their respective pathological significance. METHODS: We analyzed 135 liver biopsy specimens. A portion of the liver biopsy specimen was examined using transmission electron microscopy (TEM) to investigate intranuclear lipid droplets in hepatocytes. Nuclear inclusion bodies with clear boundaries and unstained areas on hematoxylin and eosin staining were identified as nuclear glycogen. RESULTS: TEM revealed nucleoplasmic lipid droplets (nLD) in 65% of liver biopsy specimens and invagination of cytoplasmic lipid droplets into the nucleus in 30% of specimens. In contrast, light microscopy detected GN in 82% of specimens. No significant correlations were observed between the frequencies of the two types of intranuclear lipid droplets and nuclear glycogen levels. A significant positive correlation was observed between the frequency of nLD and transaminase levels. Glycogenated nuclei were frequently observed in liver biopsy specimens from patients with MASLD; however, their frequency did not significantly correlate with the degree of hepatic steatosis. Instead, a significant positive correlation was observed between nuclear glycogen and blood HbA1c levels. CONCLUSIONS: The two types of intranuclear lipid droplets and nuclear glycogen observed in liver biopsy specimens showed no significant correlation in their formation frequencies, suggesting that they possess distinct pathological significance.

Region-specific assessment of the mechanical properties of each hamstring muscle in human cadavers using shear wave elastography.

Gakuto Nakao, Taiki Kodesho, Kazuma Yamagata, Risa Adachi, Koki Ishiyama, Kazuyoshi Kozawa, Kota Watanabe, Yuki Ohsaki, Masaki Katayose, Keigo Taniguchi

Clinical biomechanics (Bristol, Avon) 127 106586 - 106586 2025.07 [International journal]

BACKGROUND: Understanding regional mechanical properties of individual hamstring muscles is essential for accurately interpreting their functional behavior during elongation. However, how mechanical stress varies within muscles during elongation remains unclear. This study aimed to examine whether mechanical stresses differ among the hamstring muscles and at various regions within each muscle. METHODS: Fifteen cadavers were dissected to study the biceps femoris long head, semitendinosus, and semimembranosus muscles. Proximal and distal tendons were attached to a mechanical testing machine, and muscles were stretched from slack length to 8 % strain. Muscle length was measured with a tape measure, and anatomical cross-sectional areas at proximal (33 %) and distal (67 %) regions were determined using B-mode ultrasonography. Strain and stress were calculated to assess mechanical properties, and shear modulus was measured using shear wave elastography at the same regions. FINDINGS: A linear correlation between shear modulus and stress was found for all hamstring muscles (P < 0.01). Significant interactions among muscle, region, and strain were observed, with post-hoc tests revealing that the biceps femoris long head and semimembranosus had higher shear modulus than the semitendinosus after 0.5 % strain. The proximal biceps femoris long head showed increased shear modulus after 5 % strain, and proximal semimembranosus showed higher values after 0.5 % strain compared with the distal region. INTERPRETATION: The study findings reveal region-specific variations in the mechanical properties both among and within the hamstring muscles. Combining shear wave elastography with mechanical testing offers a non-destructive approach for characterizing these variations in passive muscle behavior.

Ultrasound-guided serratus posterior superior muscle block: an anatomical study investigating the extent of injected dye and the mechanism of action of a simulated injection in Thiel soft-embalmed cadavers.

Atsushi Sawada, Tatsuya Kunigo, Yuki Ohsaki, Kanna Nagaishi, Michiaki Yamakage

Journal of anesthesia 2025.04 [Domestic journal]

PURPOSE: The extent of local anesthetic spread and mechanism of action of serratus posterior superior muscle (SPSM) block is still debatable. This cadaveric study aimed to evaluate the anatomical spread of 30 or 20 mL of dye following a simulated SPSM block in Thiel soft-embalmed cadavers. METHODS: Simulated SPSM block injections were administered bilaterally in four cadavers (left side: 30 mL, right side: 20 mL). Anatomical dissection was performed to evaluate the extent of spread of the injected dye over the ribcage, and to document staining of the musculature of the back following a simulated SPSM block. RESULTS: The extents of spread (mean ± SD) of 30 mL and 20 mL of dye over the ribcage were 8.5 ± 3.9 cm and 5.5 ± 1.6 cm, respectively. Dye spread to the peri-scapular fascia was observed in all four of the simulated SPSM blocks with 30 mL of dye, but not with 20 mL. Dye spread into the rhomboid major muscle was observed in two of the simulated SPSM blocks with 30 mL of dye. CONCLUSION: Our findings suggest that the SPSM block using 30 mL of dye has a tendency to spread wider compared to the SPSM block using 20 mL of injectate, and that the block might serve as an interfascial block rather than a segmental nerve block. Further studies in a large sample of human participants are required to confirm the optimal volume of local anesthetic in the SPSM block.

Ultrasound-assisted middle thoracic epidural catheter placement utilizing the most dorsal sites of bilateral transverse process roots as anatomical landmarks: A cadaveric observational study and a clinical randomized controlled trial.

Tatsuya Kunigo, Yusuke Yoshikawa, Shunichi Niki, Masahiro Ohtani, Mami Muraki, Asako Nitta, Yuki Ohsaki, Kanna Nagaishi, Michiaki Yamakage

Journal of clinical anesthesia 101 111740 - 111740 2025.02 [International journal]

STUDY OBJECTIVE: We developed an innovative method for ultrasound-assisted thoracic epidural catheter placement and assessed its potential to reduce procedural duration for trainees. DESIGN: A cadaveric observational study and a clinical randomized controlled trial. SETTING: Sapporo Medical University Hospital. PATIENTS: A total of 52 adult patients scheduled for thoracic or abdominal surgery and four cadavers. INTERVENTIONS: Patients were randomly assigned to either group receiving conventional palpation (conventional group) or combination of the ultrasound examination and conventional palpation (ultrasound group). MEASUREMENTS: The primary outcome was total procedure time (sum of skin marking time and needling time) by trainees. The secondary outcomes were (1) skin marking time, (2) needling time, (3) multiple skin punctures, (4) needle redirection, (5) complications, and (6) failed cases. MAIN RESULTS: Through dissection of four cadavers, the most dorsal site of the transverse process root was identifiable by ultrasound and the reliable indicator of the interlaminar space. We devised ultrasound-assisted middle thoracic epidural catheter placement utilizing the most dorsal sites of bilateral transverse process roots as anatomical landmarks. Trainees in the ultrasound group had significantly longer skin marking time and significantly shorter needling time than those in the conventional group (107 [87-158] vs 46 s [34-54] s, p < 0.001 and 197 [156-328] vs 341 [303-488] s, p = 0.003). Consequently, there was no significant difference between the two groups in total procedure time (326 [263-467] s vs 391 [354-533] s, p = 0.167). Moreover, the probability of trainee failure in epidural anesthesia was significantly lower in the ultrasound group (2/26 [17.7 %] vs 10/26 [38.5 %], p = 0.019). CONCLUSIONS: Our novel technique for thoracic epidural catheter placement resulted in expedited needling and enhanced success rates among trainees, although there was no significant difference between total procedure time when using ultrasound guidance and that when using conventional palpation.

Passive muscle tension changes in the biceps femoris long head after biceps femoris short head detachment: A human cadaver study.

Gakuto Nakao, Kazuma Yamagata, Risa Adachi, Koki Ishiyama, Kazuyoshi Kozawa, Kota Watanabe, Yuki Ohsaki, Kousuke Shiwaku, Norio Hayashi, Masaki Katayose, Keigo Taniguchi

Journal of biomechanics 179 112480 - 112480 2025.01 [International journal]

The functional role of the biceps femoris short head (BFsh) remains unclear. Clarifying the functional role of each biceps femoris head may provide useful insights into the reduction of biceps femoris long head (BFlh) injuries. This study aimed to clarify whether the passive tension in the BFlh would change with BFsh detachment using cadavers. The shear modulus of the BFlh and BFsh was measured using ultrasonic shear wave elastography as an index of passive tension in three tissue processing conditions (intact, removal of all tissues from skin to deep fascia, and BFsh detachment) in four limb positions, with hip [H0°, H90°] and knee [K0°, K90°] joint angles under each tissue processing condition. The measurement site was the distal 30 % of the line connecting the sciatic tuberosity (100 %) and fibular head (0 %). Three-way analysis of variance was conducted with muscles, tissue processing, and positions as factors, which revealed a significant interaction (P < 0.01). The post-test results indicated that the BFlh was significantly higher than the BFsh at H90° and K0° before tissue processing; however, no difference was observed between the muscles after skin and deep fascia removal. After BFsh detachment, the shear modulus of the BFsh decreased, whereas that of the BFlh significantly increased (P < 0.01), suggesting that the BFsh might be involved in the passive tension reduction of the BFlh in a lengthened position, as the shear modulus of the BFlh increased after detachment.

Effects of superficial tissue and intermuscular connections on rectus femoris muscle shear modulus heterogeneity.

Taiki Kodesho, Takuya Kato, Gakuto Nakao, Yu Yokoyama, Yuhei Saito, Kota Watanabe, Yuki Ohsaki, Masaki Katayose, Keigo Taniguchi

Journal of ultrasound 27 ( 3 ) 449 - 455 2024.09 [International journal]

INTRODUCTION: Intramuscular heterogeneity exists in the shear modulus of the rectus femoris (RF) muscle. However, the underlying heterogeneity mechanisms are not entirely understood. Previous research has reported that detachment of superficial tissues reduces the shear modulus by 50%. The aim of this study was to examine the effects of the skin, deep fascia, and intermuscular connections on the shear modulus of the RF at multiple sites. MATERIALS AND METHODS: Eleven donors were fixed using the Thiel method. Measurements were performed at 0°, 60°, and 120° knee flexion in a neutral hip position. Tissue processing was performed under four conditions: superficial tissue (CONT), skin off (SKIN), deep fascia detachment (FASC), and intermuscular connections detachment (ALL). The shear modulus at the proximal, central, and distal regions were measured using ultrasound shear wave elastography. The study was approved by the Sapporo Medical University Ethical Committee. RESULTS: Three-way ANOVA revealed no significant interaction between treatment, site, and angle (P = 0.156), treatment and angle (P = 0.067), or site and angle (P = 0.441). There was a significant effect of treatment (P < 0.001), site (P = 0.010), and angle (P < 0.001) and interaction between treatment and site (P < 0.001). The proximal shear modulus was greater than the central for CONT. There were no significant differences between the measurement sites for SKIN. The distal shear modulus was greater than the proximal for FASC. The distal shear modulus was also greater than the proximal and central for ALL. CONCLUSIONS: Intramuscular regional differences that influence superficial tissue and intermuscular connections of RF elasticity heterogeneity were observed.

Validity of Elastic Imaging Evaluation of Hamstring Muscles With Knee Contracture Using Ultrasound Shear Wave Elastography.

Gakuto Nakao, Taiki Kodesho, Kazuma Yamagata, Kota Watanabe, Yuki Ohsaki, Masaki Katayose, Keigo Taniguchi

Cureus 16 ( 8 ) e68343 2024.08 [International journal]

PURPOSE: This study used ultrasound shear wave elastography (SWE) to evaluate the mechanical properties of hamstring muscles from cadaveric specimens with knee flexion contractures. METHODS: Hamstring muscles for tensile testing were harvested from Thiel soft-embalmed cadavers with and without knee flexion contracture. Muscle specimens were mounted on a testing machine. The initial load detected when a tensile load was applied to the distal end was used as the slack length. The cross-sectional areas of the muscle at slack length were measured at the proximal and distal sites using B-mode ultrasonography. Subsequently, the muscle specimen was elongated from the slack length to 8% strain, with the shear modulus measured using SWE. Young's modulus (stress/strain) was calculated based on the displacement and tensile force obtained from the tensile test. RESULTS: Regression analysis showed a significant positive linear relationship between the Young's and shear moduli for all specimens at all the sites (P < 0.01 and coefficient of determination: 0.95-0.99). The Young's and average shear moduli at the proximal and distal sites were higher in all hamstring muscles with contractures than in those without contractures. CONCLUSIONS: SWE can be used to estimate Young's moduli of hamstring muscles with contractures. Muscle specimens with contractures exhibited higher resistance to elongation, thereby indicating that their mechanical properties differed from those of muscles without contractures.

Correction: Relationship between shear elastic modulus and passive muscle force in human hamstring muscles using a Thiel soft-embalmed cadaver.

Gakuto Nakao, Taiki Kodesho, Takuya Kato, Yu Yokoyama, Yuhei Saito, Yuki Ohsaki, Kota Watanabe, Masaki Katayose, Keigo Taniguchi

Journal of medical ultrasonics (2001) 51 ( 3 ) 541 - 541 2024.07 [Domestic journal]

Stress-strain relationship of individual hamstring muscles: A human cadaver study.

Gakuto Nakao, Taiki Kodesho, Kazuma Yamagata, Kota Watanabe, Yuki Ohsaki, Masaki Katayose, Keigo Taniguchi

Journal of the mechanical behavior of biomedical materials 153 106473 - 106473 2024.05 [International journal]

The incidence of hamstring muscle strain varies among muscles, suggesting that the mechanical stresses associated with elongation may differ among muscles. However, the passive mechanical properties of whole human muscles have rarely been directly measured and clarified. This study aimed to clarify the stress-strain relationship of the hamstring muscles using a soft-embalmed Thiel cadaver. The long heads of the biceps femoris (BFlh), semimembranosus (SM), and semitendinosus (ST) muscles were dissected from eight cadavers. The proximal and distal hamstring tendons were affixed to the mechanical testing machine. Slack length was defined as the muscle length at the initial loading point detected upon the application of a tensile load. Muscle length was measured using a tape measure, and the anatomical cross-sectional area (ACSA) of the muscle was measured at the proximal and distal sites using B-mode ultrasonography. In the loading protocol, the muscle was elongated from its slack length to a maximum of 8% strain at an average rate of 0.83 L0/s, and the amount of displacement and tensile load were measured for each muscle. Further, the strain (%, displacement/slack muscle length) and stress (kPa, tensile load/ACSA) were calculated to evaluate the mechanical properties. Two-way repeated-measures analysis of variance (ANOVA) was used to compare stress changes with increasing muscle strain. A significant interaction between the muscle and strain factors was observed with respect to stress. Post-hoc tests revealed higher stresses in the BFlh and SM than in ST after 3% strain (P < 0.01). However, no significant differences were observed between the BFlh and SM groups. At 8% strain, the BFlh, SM, and ST exhibited stresses of 63.7 ± 12.1, 53.7 ± 23.2, and 21.0 ± 11.9 kPa, respectively. The results indicate that the stress changes associated with muscle strain differed among muscles. In particular, the stress applied to the three muscles at the same strain was found to be higher in the BFlh and SM. Thus, these findings suggest that increased mechanical stress during elongation may contribute to the frequent occurrence of muscle strain in BFlh and SM.

Fish oil-derived n-3 polyunsaturated fatty acids downregulate aquaporin 9 protein expression of liver and white adipose tissues in diabetic KK mice and 3T3-L1 adipocytes.

Yuzuru Iizuka, Satoshi Hirako, Hyounju Kim, Nobuhiro Wada, Yuki Ohsaki, Naoko Yanagisawa

The Journal of nutritional biochemistry 124 109514 - 109514 2024.02 [International journal]

Aquaporin 9 (AQP9) is an integral membrane protein that facilitates glycerol transport in hepatocytes and adipocytes. Glycerol is necessary as a substrate for gluconeogenesis in the physiological fasted state, suggesting that inhibiting AQP9 function may be beneficial for treating type 2 diabetes associated with fasting hyperglycemia. The n-3 polyunsaturated fatty acids (PUFAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are rich in fish oil and lower the risk of metabolic syndrome; however, the effects of EPA and DHA on AQP9 expression in obese and type 2 diabetes are unclear. The KK mouse is an animal model of obesity and type 2 diabetes because of the polymorphisms on leptin receptor gene, which results in a part of cause for obese and diabetic conditions. In this study, we determined the effect of fish oil-derived n-3 PUFA on AQP9 protein expression in the liver and white adipose tissue (WAT) of KK mice and mouse 3T3-L1 adipocytes. The expression of AQP9 protein in the liver, epididymal WAT, and inguinal WAT were markedly decreased following fish oil administration. We also demonstrated that n-3 PUFAs, such as DHA, and to a lesser extent EPA, downregulated AQP9 protein expression in 3T3-L1 adipocytes. Our results suggest that fish oil-derived n-3 PUFAs may regulate the protein expressions of AQP9 in glycerol metabolism-related organs in KK mice and 3T3-L1 adipocytes.

The interplay between the epithelial permeability barrier, cell migration and mitochondrial metabolism of growth factors and their inhibitors in a human endometrial carcinoma cell line.

Takumi Konno, Takayuki Kohno, Shin Kikuchi, Arisa Kura, Kimihito Saito, Tadahi Okada, Hiroshi Shimada, Yuya Yamazaki, Tomoki Sugiyama, Motoki Matsuura, Yuki Ohsaki, Tsuyoshi Saito, Takashi Kojima

Tissue barriers 2304443 - 2304443 2024.01 [International journal]

It is known that there are abnormalities of tight junction functions, cell migration and mitochondrial metabolism in human endometriosis and endometrial carcinoma. In this study, we investigated the effects of growth factors and their inhibitors on the epithelial permeability barrier, cell migration and mitochondrial metabolism in 2D and 2.5D cultures of human endometrioid endometrial carcinoma Sawano cells. We also investigated the changes of bicellular and tricellular tight junction molecules and ciliogenesis induced by these inhibitors. The growth factors TGF-β and EGF affected the epithelial permeability barrier, cell migration and expression of bicellular and tricellular tight junction molecules in 2D and 2.5D cultures of Sawano cells. EW-7197 (a TGF-β receptor inhibitor), AG1478 (an EGFR inhibitor) and SP600125 (a JNK inhibitor) affected the epithelial permeability barrier, cell migration and mitochondrial metabolism and prevented the changes induced by TGF-β and EGF in 2D and 2.5D cultures. EW-7197 and AG1478 induced ciliogenesis in 2.5D cultures. In conclusion, TGF-β and EGF promoted the malignancy of endometrial cancer via interplay among the epithelial permeability barrier, cell migration and mitochondrial metabolism. EW-7197 and AG1478 may be useful as novel therapeutic treatments options for endometrial cancer.

I-gel Plus acts as a superior conduit for fiberoptic intubation than standard i-gel.

Tomohiro Chaki, Shunsuke Tachibana, Sho Kumita, Satoshi Sato, Tomoki Hirahata, Yuta Ikeshima, Yuki Ohsaki, Michiaki Yamakage

Scientific reports 13 ( 1 ) 18381 - 18381 2023.10 [International journal]

The supraglottic airway (SGA) is widely used. I-gel Plus is a next-generation i-gel with some improvements, including facilitation of fiberoptic tracheal intubation (FOI). To compare the performance of i-gel Plus and standard i-gel as conduits for FOI, a Thiel-embalmed cadaveric study was conducted. Twenty-two anesthesiologists were enrolled as operators in Experiment 1. The i-gel Plus and standard i-gel were inserted into one cadaver, and the FOI was performed through each SGA. The primary outcome was time required for FOI. The secondary outcomes were the number of attempts and visual analog scale (VAS) score for difficulty in FOI. Moreover, fiberoptic views of the vocal cords in each SGA were assessed by an attending anesthesiologist using nine cadavers in Experiment 2. The percentage of glottic opening (POGO) score without fiberscope tip upward flexion and upward angle of the fiberscope tip to obtain a 100% POGO score were evaluated as secondary outcomes. The time for FOI through i-gel Plus was significantly shorter than that through standard i-gel (median (IQR), i-gel Plus: 30.3 (25.4-39.0) s, vs standard i-gel: 54.7 (29.6-135.0) s; median of differences, 24.4 s; adjusted 95% confidence interval, 3.0-105.7; adjusted P = 0.040). Although the number of attempts for successful FOI was not significantly different, the VAS score for difficulty in the i-gel Plus group was significantly lower (easier) than that in the standard i-gel group. Moreover, i-gel Plus required a significantly smaller upward angle of the fiberscope tip to obtain a 100% POGO score. FOI can be performed more easily using i-gel Plus than using standard i-gel because of the improved fiberoptic visibility of vocal cords.

Modified thoracoabdominal nerve block through perichondrial approach (M-TAPA): an anatomical study to evaluate the spread of dye after a simulated injection in soft embalmed Thiel cadavers.

Atsushi Sawada, Sho Kumita, Asako Nitta, Yuki Ohsaki, Michiaki Yamakage

Regional anesthesia and pain medicine 48 ( 8 ) 403 - 407 2023.08 [International journal]

BACKGROUND AND OBJECTIVES: There is still no consensus on the analgesic range and mechanisms of action of modified thoracoabdominal nerve block through perichondrial approach (M-TAPA). This cadaveric study aimed to determine the spread of an injectate following simulated M-TAPA. METHODS: Simulated M-TAPA injections (n=8) were administered on both sides of soft embalmed Thiel cadavers with 25 mL of a saline-soluble dye. Anatomic dissection was performed to document staining (deeply, faintly, or not stained) of the anterior cutaneous branches of the thoracoabdominal nerves and determine the extent of the injectate spread of the dye to the intercostal space in the thoracic cage following a simulated M-TAPA. RESULTS: The median (IQR) dermatome of the stained segmental nerve was T10 (T8-T11) and the median (IQR) number of stained segmental nerves was 3 (4-2). The T9, T10 and T11 segmental nerves were stained in 75%, 100% and 62.5% of simulated M-TAPA, respectively. Conversely, the T8 segmental nerve was stained in only 25% of simulated M-TAPA. No injectate spread of dye to the intercostal space in the thoracic cage was observed in eight simulated injections of M-TAPA. CONCLUSION: Our findings suggest that M-TAPA most likely involves the T9, T10 and T11 segmental nerves and that the local anesthetic may not spread to the intercostal space in the thoracic cage in M-TAPA. Further studies are required to confirm the precise mechanism of action and efficacy of M-TAPA in a large sample of human participants.

Relationship between shear elastic modulus and passive muscle force in human hamstring muscles using a Thiel soft-embalmed cadaver.

Gakuto Nakao, Taiki Kodesho, Takuya Kato, Yu Yokoyama, Yuhei Saito, Yuki Ohsaki, Kota Watanabe, Masaki Katayose, Keigo Taniguchi

Journal of medical ultrasonics (2001) 50 ( 3 ) 275 - 283 2023.07 [Domestic journal]

PURPOSE: Assessing muscle flexibility and architecture is important for hamstring strain injury (HSI) prevention. We investigated the relationship between shear modulus and passive force in hamstring muscles at different sites and the effect of muscle architecture on the slope of the shear modulus-passive force using shear wave elastography (SWE). METHODS: The biceps femoris long head (BFlh), semitendinosus (ST), and semimembranosus (SM) muscles were dissected from nine Thiel-embalmed cadavers and fixed to a custom-made mechanical testing machine. Calibrated weights (0-1800 g) were applied gradually in 150-g increments. The shear modulus and anatomical cross-sectional area (ACSA) were measured at proximal, central, and distal points using SWE. The muscle mass and length were measured before the loading test. The shear modulus-passive load relationship of each tested muscle region was analyzed by fitting a least-squares regression line. The increase in shear modulus slope per unit load was calculated and compared between the muscles before and after normalization by the muscle mass, length, and ACSA. RESULTS: The shear modulus and passive force for all hamstring muscles in each region showed a statistically significant linear correlation. Furthermore, the increase in shear modulus slope was greater for BFlh and ST than for SM (P < 0.05), but after normalization by the muscle length and ACSA, there were no significant differences among the muscles. CONCLUSION: The local mechanical properties of individual hamstring muscles can be indirectly estimated using SWE, and the slope of increase in shear modulus reflects characteristics of the muscle architecture.

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 ) 2023.04

Authorship： Lead author , Corresponding author

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.

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 2022.11

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 2022.06 [International journal]

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.

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 ) 2021.01 [Refereed] [International journal]

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.

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 2020.09 [Refereed] [International journal]

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.

Intracellular Organelles Driven by Liquid-Liquid Phase Separation

Shunsuke F. SHIMOBAYASHI, Yuki OHSAKI

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

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