Review
Pharmacology & Pharmacy
Renshuai Zhang, Jun Zeng, Wenjing Liu, Jingsen Meng, Chao Wang, Lingyu Shi, Shanbo Yang, Jing Chang, Dongming Xing
Summary: Lipid metabolism plays a significant role in cancer development, and cholesterol is involved in the evolution of malignancies. NPC1L1, a cholesterol transporter protein, plays a crucial part in cholesterol absorption and has been shown to be important in tumor prognosis. It has the potential to be a new therapeutic target and cancer marker.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Medicine, Research & Experimental
Renshuai Zhang, Wenjing Liu, Jun Zeng, Jingsen Meng, Lingyu Shi, Shanbo Yang, Jing Chang, Chao Wang, Kunyue Xing, Jialian Wen, Ning Liu, Bing Liang, Dongming Xing
Summary: NPC1L1 is a crucial protein involved in sterol lipid absorption and plays an important role in intestinal cholesterol absorption. Screening NPC1L1 inhibitors is critical for understanding lipid metabolism, developing cholesterol-lowering medicines, and treating cardiovascular diseases. This study summarized existing methodologies for screening NPC1L1 inhibitors and evaluated their challenges, aiming to assist the development of novel cholesterol-lowering medications and therapeutic strategies for hypercholesterolemia and other cholesterol-related metabolic disorders.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Cell Biology
Alexander L. Ticho, Nathan Calzadilla, Pooja Malhotra, Hyunjin Lee, Arivarasu Natarajan Anbazhagan, Seema Saksena, Pradeep K. Dudeja, Daesung Lee, Ravinder K. Gill, Waddah A. Alrefai
Summary: Research suggests that 27-alkyne cholesterol acts as a substrate for NPC1L1 in cholesterol absorption, serving as a potential nonradioactive tracer for measuring cholesterol absorption in both in vitro and in vivo models.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2021)
Article
Cell Biology
Weiyi Shen, Wentao Shao, Qihan Wang, Bo Wang, Gang Zhao, Aihua Gu, Zhaoyan Jiang, Hai Hu
Summary: This study demonstrates that diosgenin (DG) can prevent the formation of gallstones in mice by inhibiting cholesterol absorption in the intestine and regulating cholesterol metabolism genes. DG also has the ability to modulate gut microbiota profiles and inhibit LPS-mediated STAT3 activation and Npc1l1 expression.
JOURNAL OF BIOMEDICAL SCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Deyan Yavorov-Dayliev, Fermin I. Milagro, Miguel Lopez-Yoldi, Inigo Clemente, Jose Ignacio Riezu-Boj, Josune Ayo, Maria Oneca, Paula Aranaz
Summary: This study evaluated the effects of the probiotic strain Pediococcus acidilactici (pA1c (R)) on diet-induced obesity in rats. The results showed that supplementation with pA1c (R) improved adiposity, cholesterol and lipid metabolism, inflammation, and gut microbiota composition. Additionally, pA1c (R) activation of fatty acid beta-oxidation was observed in adipose tissue and the liver.
Article
Chemistry, Medicinal
Jingsen Meng, Jiazhen Xu, Shanbo Yang, Wenjing Liu, Jun Zeng, Lingyu Shi, Jing Chang, Renshuai Zhang, Dongming Xing
Summary: Emodin inhibits cholesterol uptake by influencing NPC1L1 cholesterol transport, suggesting its potential in lowering cholesterol.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Biochemistry & Molecular Biology
Wenjing Liu, Bing Liang, Jun Zeng, Jingsen Meng, Lingyu Shi, Shanbo Yang, Jing Chang, Chao Wang, Xiaokun Hu, Xufu Wang, Na Han, Chenghui Lu, Jiao Li, Congcong Wang, Huanting Li, Renshuai Zhang, Dongming Xing
Summary: Parthenolide (PTL), a naturally occurring small molecule from Tanacetum parthenium, has shown potential in lowering cholesterol levels by inhibiting cellular uptake of cholesterol. Its interaction with NPC1L1 supports its potential as a therapeutic inhibitor for hypercholesterolemia.
Review
Food Science & Technology
Kaihui Cao, Kaiping Zhang, Muran Ma, Junjie Ma, Jianjun Tian, Ye Jin
Summary: Lactobacillus, as a normal flora in the gut, plays a significant role in regulating metabolism and cholesterol content in the human body by mediating the expression of genes involved in cholesterol synthesis, metabolism, and absorption. This can help inhibit cholesterol absorption and maintain human health.
FOOD SCIENCE & NUTRITION
(2021)
Article
Biochemistry & Molecular Biology
Pingfan Mo, Hongtan Chen, Xin Jiang, Fengling Hu, Fenming Zhang, Guodong Shan, Wenguo Chen, Sha Li, Yiqiao Li, Guoqiang Xu
Summary: This study found that ezetimibe can effectively prevent cholesterol gallstone disease. LD induces the degradation of hepatic NPC1L1 via the FGF15-FGFR4 pathway. These findings contribute to a better understanding of the pathogenesis of CGD and the identification of effective strategies for prevention and treatment of the disease.
LIPIDS IN HEALTH AND DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Michiyo Takahashi, Mayumi Nagata, Tetsu Kinoshita, Takehiko Kaneko, Toshikazu Suzuki
Summary: Genetic polymorphisms are associated with CoQ(10) serum levels after long-term supplementation, with some genes linked to a significant increase in CoQ(10) levels in women, aiding in distinguishing high- and low-responders to CoQ(10) bioavailability in females but not males.
Article
Cell Biology
Lin Jia, Yinyan Ma, Jamie Haywood, Long Jiang, Bingzhong Xue, Hang Shi, Paul A. Dawson, Liqing Yu
Summary: NPC1L1 knockout mice fed a high-fat diet exhibit increased energy expenditure and bile acid pool size, with elevated expression of genes related to energy expenditure in brown adipose tissue, potentially contributing to protection against HFD-induced obesity.
Article
Biochemistry & Molecular Biology
Xiuying Kui, Dandan Qiu, Wenguang Wang, Na Li, Pinfen Tong, Xiaomei Sun, Liangzi Jin, Wei Deng, Jiejie Dai, Caixia Lu
Summary: The tree shrew NPC1L1 has a higher homology with human NPC1L1 compared to rodents. Its expression is highest in the small intestine, with detectable levels in the lung and pancreas. These findings are valuable for understanding the function of tsNPC1L1 in cholesterol absorption and HCV infection.
MOLECULAR BIOLOGY REPORTS
(2021)
Article
Chemistry, Organic
Chen-Chen Gu, Jun Zeng, Xiao-Ping Peng, Yan-Jun Sun, Shuang-Zhi Yuan, Xiu-Ning Wang, Ren-Shuai Zhang, Hong-Xiang Lou, Gang Li
Summary: Metabolic profiling of the fungus Chaetomium nigricolor F5 led to the discovery of five new cytochalasans, as well as two known compounds. Compound 5 showed promising inhibition activity against the cholesterol transporter NPC1L1, expanding the function of cytochalasans.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Review
Nutrition & Dietetics
Yoshimi Nakagawa, Masaya Araki, Song-iee Han, Yuhei Mizunoe, Hitoshi Shimano
Summary: CREBH is a membrane-bound transcriptional factor expressed in the liver and small intestine, regulating triglyceride metabolism and controlled by circadian rhythm. Deficiency leads to hypertriglyceridemia and fatty liver, while knock out mice exhibit severe atherosclerosis, indicating the crucial role of CREBH in systemic lipid homeostasis.
Review
Microbiology
Catherine Juste, Philippe Gerard
Summary: Cholesterol in the colon is metabolized by bacteria into coprostanol, with variable conversion rates in human populations. Two major conversion pathways have been proposed, but there is still much unknown in this field.
Article
Peripheral Vascular Disease
Kiminori Kato, Tomoaki Ishigami, Takashi Kobayashi, Minoru Tahiro, Shigemi Tashiro, Takaho Yamada, Midori Iwanaga, Satoru Kodama, Kazuya Fujihara, Koji Sato, Hirohito Sone
Summary: Salt excretion using spot urine (e-NaCl) is a convenient method to determine salt intake. In this study, e-NaCl was measured during health checkups and compared with seasonal changes in blood pressure. The results showed that e-NaCl decreased in summer, possibly due to reduced burden on the kidneys for salt excretion caused by sweating, which may be related to decreases in blood pressure.
HYPERTENSION RESEARCH
(2023)
Article
Endocrinology & Metabolism
Taeko Osawa, Kazuya Fujihara, Mayuko Harada Yamada, Yuta Yaguchi, Takaaki Sato, Masaru Kitazawa, Yasuhiro Matsubayashi, Takaho Yamada, Satoru Kodama, Hirohito Sone
Summary: This study aimed to investigate the associations between urinary protein and reduced glomerular filtration rate (eGFR) and the risk of starting dialysis. The results showed that the severity of urinary protein and eGFR were independent predictors of starting dialysis, and the risk was higher in individuals with diabetes mellitus.
DIABETOLOGY INTERNATIONAL
(2023)
Article
Endocrinology & Metabolism
Maki Kawasaki, Naoko Arata, Takashi Sugiyama, Tatsumi Moriya, Atsuo Itakuda, Ichiro Yasuhi, Yasuko Uchigata, Eiji Kawasaki, Hirohito Sone, Yuji Hiramatsu
Summary: This study aimed to establish a prospective registry system for gestational diabetes mellitus (GDM) in Japan and to clarify the actual status of GDM according to the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. The results showed that the risk of low birth weight (LBW) and small-for-gestational age in the GDM group was significantly higher than in the normal glucose tolerance (NGT) group.
JOURNAL OF DIABETES INVESTIGATION
(2023)
Article
Endocrinology & Metabolism
Kazuya Fujihara, Laymon Khin, Koshiro Murai, Yurie Yamazaki, Kahori Tsuruoka, Noriko Yagyuda, Katsuya Yamazaki, Hiroshi Maegawa, Shiro Tanaka, Satoru Kodama, Hirohito Sone
Summary: This study aimed to determine the incidence of remission and 1-year relapse in patients with type 2 diabetes and associated factors. The overall incidence of remission in Japanese patients was 10.5 per 1000 person-years, with higher rates for those with HbA1c levels of 48 to 53 mmol/mol (6.5% to 6.9%), those taking no glucose-lowering drugs at baseline, and those with a =10% BMI reduction in 1 year. Shorter duration, lower baseline HbA1c, higher baseline BMI, greater BMI reduction at 1 year, and no glucose-lowering drugs at baseline were significantly associated with remission. Among those with remission, approximately two-thirds relapsed within 1 year. Longer duration, lower baseline BMI, and lower BMI reduction at 1 year were significantly associated with relapse.
DIABETES OBESITY & METABOLISM
(2023)
Article
Medicine, General & Internal
Yuhki Sakurai, Nobumasa Ohara, Yumi Fukai, Yasuhiro Seki, Katsuhiko Akiyama, Yuichiro Yoneoka, Toshinori Takada, Takashi Tani, Kenshi Terajima, Tetsutaro Ozawa, Hirohito Sone
Summary: A 56-year-old man with anorexia for 2.5 months presented with sweating, weakness, left hemiplegia, and hemispatial neglect. Magnetic resonance imaging showed no abnormalities, but magnetic resonance angiography revealed narrowing of the right middle cerebral artery. Neurological symptoms and arterial narrowing resolved after correction of hypoglycemia. Adrenal insufficiency was identified through endocrinological examinations. Hemiplegia is a rare but important neurological manifestation of hypoglycemia, possibly caused by combined hypoglycemia and decreased blood flow leading to regional neuroglycopenia and ischemia.
Article
Sport Sciences
Takaaki Sato, Kazuya Fujihara, Mayuko Harada Yamada, Kaori Chou, Yuta Yaguchi, Masaru Kitazawa, Hajime Ishiguro, Taeko Osawa, Takaho Yamada, Satoru Kodama, Kiminori Kato, Hirohito Sone
Summary: A new Physical Score (PS) was developed and its association with metabolic diseases among Japanese individuals was elucidated. The PS was calculated based on physical fitness indicators and showed a significant association with an increased risk of metabolic diseases, especially metabolic syndrome. The PS was found to be a useful and simple non-invasive tool for screening Japanese people for metabolic diseases.
JOURNAL OF SPORTS SCIENCE AND MEDICINE
(2023)
Article
Public, Environmental & Occupational Health
Kazuya Fujihara, Mayuko Yamada Harada, Chika Horikawa, Midori Iwanaga, Hirofumi Tanaka, Hitoshi Nomura, Yasuharu Sui, Kyouhei Tanabe, Takaho Yamada, Satoru Kodama, Kiminori Kato, Hirohito Sone
Summary: This study developed a machine learning model to predict weight change over three years. It found that lifestyle had a significant impact on weight in individuals with high BMI and in young people. The model showed comparable accuracy to multiple regression, suggesting its potential for personalized weight management.
FRONTIERS IN PUBLIC HEALTH
(2023)
Correction
Nutrition & Dietetics
Kanako Sumi, Yuiko Hatanaka, Reina Takahashi, Naoko Wada, Chihiro Ono, Yuri Sakamoto, Hirohito Sone, Kaoruko Iida
FRONTIERS IN NUTRITION
(2023)
Article
Endocrinology & Metabolism
Kazuya Fujihara, Laymon Khin, Koshiro Murai, Yurie Yamazaki, Kahori Tsuruoka, Noriko Yagyuda, Katsuya Yamazaki, Hiroshi Maegawa, Shiro Tanaka, Satoru Kodama, Hirohito Sone, DDM Study Grp
Summary: This study found an association between the magnitude of weight loss and the incidence of remission in patients with diabetes. Significant weight loss is required, with at least 10% reduction, to achieve a 10% remission rate in clinical settings.
DIABETES OBESITY & METABOLISM
(2023)
Article
Endocrinology & Metabolism
Hiroki Yokoyama, Shin-ichi Araki, Koichi Kawai, Katsuya Yamazaki, Osamu Tomonaga, Hajime Maeda, Masafumi Ohtaki, Hiromi Obata, Hirohito Sone, Daijiro Kabata, Ayumi Shintani, Hiroshi Maegawa, JDDM Study Group
Summary: This study aimed to investigate the reduction in all-cause mortality and cardiovascular disease morbidity in type 2 diabetes patients over the past decade in real-world practice. The results showed a significant reduction in cardiovascular disease in the recent cohort, implying the impact of treatment advances.
DIABETES RESEARCH AND CLINICAL PRACTICE
(2023)
Article
Biochemistry & Molecular Biology
Yoshinori Takeuchi, Yuki Murayama, Yuichi Aita, Zahra Mehrazad Saber, Samia Karkoutly, Duhan Tao, Kyoka Katabami, Chen Ye, Akito Shikama, Yukari Masuda, Yoshihiko Izumida, Takafumi Miyamoto, Takashi Matsuzaka, Yasushi Kawakami, Hitoshi Shimano, Naoya Yahagi
Summary: This study reveals the mechanism by which the glucocorticoid receptor (GR) regulates hepatic lipogenesis through the KLF15-SREBP-1 pathway during fasting. It emphasizes the importance of the hypothalamic-pituitary-adrenal (HPA) axis-regulated GR-KLF15 pathway in the regulation of lipid metabolism in the liver during fasting.
Article
Cell Biology
Motohiro Sekiya, Yang Ma, Kenta Kainoh, Kenji Saito, Daichi Yamazaki, Tomomi Tsuyuzaki, Wanpei Chen, Putu Indah Paramita Adi Putri, Hiroshi Ohno, Takafumi Miyamoto, Yoshinori Takeuchi, Yuki Murayama, Yoko Sugano, Yoshinori Osaki, Hitoshi Iwasaki, Naoya Yahagi, Hiroaki Suzuki, Kaori Motomura, Takashi Matsuzaka, Kazuya Murata, Seiya Mizuno, Satoru Takahashi, Hitoshi Shimano
Summary: Early-stage obesity leads to increased insulin secretion as a protective mechanism for maintaining glucose homeostasis. However, this mechanism cannot be sustained and leads to eventual beta cell decompensation, a key event in the pathogenesis of diabetes. The transcriptional cofactor CtBP2 plays a crucial role in the expression of the insulin gene and its decreased expression in obesity contributes to glucose intolerance and impaired insulin secretion. Understanding the role of CtBP2 provides insights into the molecular basis of obesity and potential therapeutic targets.
Meeting Abstract
Peripheral Vascular Disease
Kiminori Kato, Tomoaki Ishigami, Hirohito Sone
JOURNAL OF HYPERTENSION
(2023)
Article
Primary Health Care
Haruka Shiozaki, Kazuya Fujihara, Mayuko Yamada-Harada, Masahiko Yamamoto, Yurie Mitsuma, Masaru Kitazawa, Yuta Yaguchi, Yasuhiro Matsubayashi, Midori Iwanaga, Takaho Yamada, Satoru Kodama, Hirohito Sone
Summary: This study aimed to investigate the independent associations of fast walking and habitual physical activity with the incidence of functional disability. The results showed that the absence of habitual physical activity and inability to walk fast were both significant risk factors for functional disability. Furthermore, the impact of these factors on disability risk varied according to age.
Article
Endocrinology & Metabolism
Liujun Chen, Lisha Li, Donghong Cui, Yiheng Huang, Haibin Tong, Haleh Zabihi, Shuxia Wang, Yadan Qi, Ted Lakowski, Lin Leng, Suixin Liu, Hong Wu, Lawrence H. Young, Richard Bucala, Dake Qi
Summary: Attenuation of adipose hormone sensitive lipase (HSL) may impair lipolysis and exacerbate obesity. Cytokine macrophage migration inhibitory factor (MIF) plays a role in regulating adipose HSL and adipocyte hypertrophy. Both intracellular and extracellular MIF have opposing effects on HSL, but extracellular action predominates to downregulate HSL and exacerbate obesity development during high-fat diet (HFD).
MOLECULAR METABOLISM
(2024)
Article
Endocrinology & Metabolism
Mengyang Tang, Yi Zhang, Rong Zhang, Yuemei Zhang, Jiangfei Zheng, Daixi Wang, Xinyu Wang, Jing Yan, Cheng Hu
Summary: This study aimed to explore the role of GPSM1 in POMC neurons and the underlying mechanisms in metabolic homeostasis. Through various molecular, biochemical, immunofluorescent, immunohistochemical analyses, and cell culture studies, the study revealed the pathophysiological role of GPSM1 in POMC neurons and its regulation of POMC neuron activity.
MOLECULAR METABOLISM
(2024)