Review
Biochemistry & Molecular Biology
Shizuya Yamashita, Manfredi Rizzo, Ta-Chen Su, Daisaku Masuda
Summary: Statins, ezetimibe, and PCSK9 inhibitors can lower LDL-C levels and reduce cardiovascular events, but residual risk factors like hypertriglyceridemia and low HDL-C still exist. Fibrates, nicotinic acids, and n-3 polyunsaturated fatty acids can be used to treat these risk factors.
Article
Medicine, General & Internal
Aruna Das Pradhan, Robert J. Glynn, Jean-Charles Fruchart, Jean G. MacFadyen, Elaine S. Zaharris, Brendan M. Everett, Stuart E. Campbell, Ryu Oshima, Pierre Amarenco, Dirk J. Blom, Eliot A. Brinton, Robert H. Eckel, Marshall B. Elam, Joao S. Felicio, Henry N. Ginsberg, Assen Goudev, Shun Ishibashi, Jacob Joseph, Tatsuhiko Kodama, Wolfgang Koenig, Lawrence A. Leiter, Alberto J. Lorenzatti, Boris Mankovsky, Nikolaus Marx, Borge G. Nordestgaard, Denes Pall, Kausik K. Ray, Raul D. Santos, Handrean Soran, Andrey Susekov, Michal Tendera, Koutaro Yokote, Nina P. Paynter, Julie E. Buring, Peter Libby, Paul M. Ridker
Summary: In patients with type 2 diabetes and high triglyceride levels, pemafibrate can reduce triglyceride, VLDL cholesterol, remnant cholesterol, and apolipoprotein C-III levels, but does not lower the incidence of cardiovascular events.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Zhe Zhang, Pan Diao, Xuguang Zhang, Takero Nakajima, Takefumi Kimura, Naoki Tanaka
Summary: Pemafibrate (PEM) is a novel lipid-lowering drug that can efficiently reduce serum triglyceride (TG) levels and increase fibroblast growth factor 21 (FGF21) without causing hepatotoxicity in mice when used at a clinically relevant dose. It binds to peroxisome proliferator-activated receptor alpha (PPAR alpha) and activates it specifically in the liver, leading to enhanced fatty acid uptake and beta-oxidation.
Article
Gastroenterology & Hepatology
Dinghui Liu, Juan Pang, Weijuan Shao, Jianqiu Gu, Yong Zeng, Housheng Hansen He, Wenhua Ling, Xiaoxian Qian, Tianru Jin
Summary: This study suggests that liraglutide-stimulated hepatic Fgf21 expression may require GLP-1R to be expressed in extrahepatic organs and reveals that hepatic FGF21 is necessary for liraglutide to lower body weight and improve hepatic lipid homeostasis. These findings advance our understanding of the mechanisms behind the function of GLP-1-based drugs in NAFLD.
Article
Immunology
Yuanyuan Liu, Shuyu Chen, Li Yu, Yao Deng, Difei Li, Xiu Yu, Dandan Chen, Ye Lu, Shengming Liu, Rongchang Chen
Summary: The study demonstrated that pemafibrate has a significant protective effect against pulmonary fibrosis in animal models and in vitro experiments, suggesting it as a potential novel candidate for the treatment of pulmonary fibrosis.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Cell Biology
Kentaro Murakami, Yusuke Sasaki, Masato Asahiyama, Wataru Yano, Toshiaki Takizawa, Wakana Kamiya, Yoshihiro Matsumura, Motonobu Anai, Tsuyoshi Osawa, Jean-Charles Fruchart, Jamila Fruchart-Najib, Hiroyuki Aburatani, Juro Sakai, Tatsuhiko Kodama, Toshiya Tanaka
Summary: In this study, the combination treatment of a selective PPAR alpha modulator and a sodium-glucose cotransporter 2 inhibitor was evaluated for its effects on the progression of non-alcoholic steatosis in a mouse model. The results showed that the combination treatment significantly alleviated hyperglycemia and hypertriglyceridemia, reduced ballooning degeneration of hepatocytes, and improved survival rates and tumor numbers in the liver. This suggests that the combination therapy has therapeutic potential in preventing the progression of non-alcoholic steatosis to hepatocellular carcinoma.
Article
Biochemistry & Molecular Biology
Deokho Lee, Ayaka Nakai, Yukihiro Miwa, Yohei Tomita, Hiromitsu Kunimi, Junhan Chen, Shin-Ichi Ikeda, Kazuo Tsubota, Kazuno Negishi, Toshihide Kurihara
Summary: Pemafibrate has shown promising potential as a preventive drug for ischemic retinopathies. It can prevent retinal degeneration and modulate the pathological mechanisms underlying retinal I/R injury.
Article
Cell Biology
Mohammad Abu-Odeh, Yuan Zhang, Shannon M. Reilly, Nima Ebadat, Omer Keinan, Joseph M. Valentine, Maziar Hafezi-Bakhtiari, Hadeel Ashayer, Lana Mamoun, Xin Zhou, Jin Zhang, Ruth T. Yu, Yang Dai, Christopher Liddle, Michael Downes, Ronald M. Evans, Steven A. Kliewer, David J. Mangelsdorf, Alan R. Saltiel
Summary: The study reveals that FGF21 in adipocytes serves as a cell-autonomous autocrine regulator of adipose tissue function. Adipose-specific deletion of the FGF21 co-receptor beta-Klotho renders mice unresponsive to beta-adrenergic stimulation, while liver-specific ablation of FGF21 does not affect mice's response to beta-adrenergic browning of adipose tissue.
Article
Agriculture, Multidisciplinary
Shuhua Tian, Yunfan Wang, Xiangfei Li, Jie Liu, Jing Wang, Yingjian Lu
Summary: Sulforaphane (SFN) can alleviate obesity complications through various mechanisms, including reducing NAFLD, inflammation, oxidative stress, adipose tissue hypertrophy, and insulin resistance, as well as regulating glucose and lipid metabolism.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2021)
Article
Cell Biology
Oliver Stohr, Rongya Tao, Ji Miao, Kyle D. Copps, Morris F. White
Summary: Fgf21 plays a crucial role in regulating metabolism during hepatic insulin resistance, as shown by studies where modestly reduced Fgf21 due to hepatic FoxO1 suppression contributed to metabolic dysregulation in LDKO mice. Restoring Fgf21 through adenoviral infection corrected metabolic issues in the mice, highlighting the importance of Fgf21-dependent plasticity and BAT function in metabolic health.
Article
Cell Biology
Mihwa Choi, Marc Schneeberger, Wei Fan, Abhijit Bugde, Laurent Gautron, Kevin Vale, Robert E. Hammer, Yuan Zhang, Jeffrey M. Friedman, David J. Mangelsdorf, Steven A. Kliewer
Summary: Animals that consume fermenting fruit and nectar are at risk of exposure to ethanol and the detrimental effects of inebriation. This report demonstrates that the hormone FGF21 plays a role in stimulating arousal from intoxication without affecting ethanol metabolism. FGF21 activates noradrenergic neurons in the locus coeruleus region, suggesting that it could be targeted pharmacologically for treating acute alcohol poisoning.
Article
Endocrinology & Metabolism
Kyle H. Flippo, Matthew J. Potthoff
Summary: FGF21, a non-canonical fibroblast growth factor, acts as an endocrine hormone signaling to various targets in the body. Initially recognized for its potential in correcting metabolic dysfunction and reducing body weight associated with diabetes and obesity, new functions of FGF21 signaling have emerged, demonstrating its ability to regulate macronutrient preference and energy balance.
Article
Pharmacology & Pharmacy
Tong Zhou, Ke Yan, Yuhan Zhang, Linfangzi Zhu, Yi Liao, Xiaoxiang Zheng, Yongxiong Chen, Xiaoxin Li, Zuguo Liu, Zhaoqiang Zhang
Summary: This study explored the potential mechanism of fenofibrate, a peroxisome proliferator-activated receptor alpha (PPAR alpha) agonist, against corneal neovascularization by investigating changes in lipid metabolism. The findings suggest that lipid metabolism disorder may contribute to suture-induced corneal neovascularization, and fenofibrate exerts anti-neovascularization and anti-inflammatory effects by regulating key enzymes in lipid metabolism and reducing lipid peroxidation damage through the PPAR alpha signaling pathway.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Food Science & Technology
Haoran Chen, Xiaofen Qi, Kaifang Guan, Yuxiang Gu, Rongchun Wang, Qiming Li, Ying Ma
Summary: The study showed that peptides from alpha-lactalbumin hydrolysate could improve lipid metabolism in HepG2 cells, with P2 and P8 being more effective in enhancing intracellular TG and PPAR alpha levels. These peptides acted as PPAR alpha ligands to regulate lipid metabolism-related gene expression, showing promise in ameliorating obesity.
JOURNAL OF FUNCTIONAL FOODS
(2021)
Article
Cardiac & Cardiovascular Systems
Koutaro Yokote, Shizuya Yamashita, Hidenori Arai, Eiichi Araki, Mitsunori Matsushita, Toshiaki Nojima, Hideki Suganami, Shun Ishibashi
Summary: The study found that pemafibrate can improve glucose metabolism and liver function in patients with hypertriglyceridemia, and increase FGF21 levels without increasing the risk of adverse events.
CARDIOVASCULAR DIABETOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yoshimi Nakagawa, Kae Kumagai, Song-iee Han, Yuhei Mizunoe, Masaya Araki, Seiya Mizuno, Hiroshi Ohno, Kazuya Matsuo, Yasunari Yamada, Jun-dal Kim, Takafumi Miyamoto, Motohiro Sekiya, Morichika Konishi, Nobuyuki Itoh, Takashi Matsuzaka, Satoru Takahashi, Hirohito Sone, Hitoshi Shimano
Summary: CREBH overexpression leads to growth delay in postnatal stage due to GH resistance and reduced IGF1 levels, despite the increase in FGF21. Inhibition of FGF21 in CREBH L-Tg mice does not correct GH resistance, indicating that CREBH may negatively regulate growth through other pathways.
Article
Multidisciplinary Sciences
Kaori Cho, Takashi Ushiki, Hajime Ishiguro, Suguru Tamura, Masaya Araki, Tatsuya Suwabe, Takayuki Katagiri, Mari Watanabe, Yoko Fujimoto, Riuko Ohashi, Yoichi Ajioka, Ippei Shimizu, Shujiro Okuda, Masayoshi Masuko, Yoshimi Nakagawa, Hideyo Hirai, Warren S. Alexander, Hitoshi Shimano, Hirohito Sone
Summary: SOCS3 protein plays a critical role in regulating obesity and diabetes, but the mechanism of action and the relationship with gut microbiota remain to be clarified.
Article
Biochemistry & Molecular Biology
Ryoma Tagawa, Masaki Kobayashi, Misako Sakurai, Maho Yoshida, Hiroki Kaneko, Yuhei Mizunoe, Yuka Nozaki, Naoyuki Okita, Yuka Sudo, Yoshikazu Higami
Summary: Long-term feeding of taurine lowers plasma cholesterol and bile acids by suppressing the FGF21/ERK pathway and upregulating Cyp7a1 expression, promoting cholesterol metabolism.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Takahiro Nagatake, Shigenobu Kishino, Emiko Urano, Haruka Murakami, Nahoko Kitamura, Kana Konishi, Harumi Ohno, Prabha Tiwari, Sakiko Morimoto, Eri Node, Jun Adachi, Yuichi Abe, Junko Isoyama, Kento Sawane, Tetsuya Honda, Asuka Inoue, Akiharu Uwamizu, Takashi Matsuzaka, Yoichi Miyamoto, So-ichiro Hirata, Azusa Saika, Yuki Shibata, Koji Hosomi, Ayu Matsunaga, Hitoshi Shimano, Makoto Arita, Junken Aoki, Masahiro Oka, Akira Matsutani, Takeshi Tomonaga, Kenji Kabashima, Motohiko Miyachi, Yasuhiro Yasutomi, Jun Ogawa, Jun Kunisawa
Summary: Microbiota plays an essential role in utilizing dietary lipids for controlling inflammatory diseases. A novel postbiotic, alpha KetoA, derived from alpha-linolenic acid, exerts anti-inflammatory effects and improves glucose intolerance through immune modulation.
MUCOSAL IMMUNOLOGY
(2022)
Article
Oncology
Ken Tanaka, Shuya Kandori, Shotaro Sakka, Satoshi Nitta, Kozaburo Tanuma, Masanobu Shiga, Yoshiyuki Nagumo, Hiromitsu Negoro, Takahiro Kojima, Bryan J. Mathis, Toru Shimazui, Makoto Watanabe, Taka-Aki Sato, Takafumi Miyamoto, Takashi Matsuzaka, Hitoshi Shimano, Hiroyuki Nishiyama
Summary: This study found that ELOVL2 was highly expressed in ccRCC, pRCC, and chRCC, and its high expression was significantly associated with a poor prognosis. Knockdown of ELOVL2 suppressed the elongation of fatty acids, increased lipid droplet production, and inhibited tumor growth. These findings provide new insights into the tumor proliferation mechanisms involving lipid metabolism and suggest ELOVL2 as a potential novel target for RCC therapy.
Editorial Material
Endocrinology & Metabolism
Yoshimi Nakagawa, Takashi Matsuzaka, Hitoshi Shimano
JOURNAL OF DIABETES INVESTIGATION
(2022)
Article
Nutrition & Dietetics
Kazuya Fujihara, Shun Nogawa, Kenji Saito, Chika Horikawa, Yasunaga Takeda, Kaori Cho, Hajime Ishiguro, Satoru Kodama, Yoshimi Nakagawa, Takashi Matsuzaka, Hitoshi Shimano, Hirohito Sone
Summary: The study revealed a significant genetic interaction between carrot intake frequency and a specific genetic variant rs4445711 in terms of BMI and obesity. However, no similar interactions were observed between the intake frequency of other vegetables and BMI or obesity.
Article
Biochemistry & Molecular Biology
Yuka Okajima, Takashi Matsuzaka, Shun Miyazaki, Kaori Motomura, Hiroshi Ohno, Rahul Sharma, Takuya Shimura, Nurani Istiqamah, Song-iee Han, Yuhei Mizunoe, Yoshinori Osaki, Hitoshi Iwasaki, Shigeru Yatoh, Hiroaki Suzuki, Hirohito Sone, Takafumi Miyamoto, Yuichi Aita, Yoshinori Takeuchi, Motohiro Sekiya, Naoya Yahagi, Yoshimi Nakagawa, Tsutomu Tomita, Hitoshi Shimano
Summary: The research found various alterations in pancreatic islet vasculature in obese insulin-resistant mice and type 2 diabetic mice, including capillary dilation, increased blood flow, and decreased endothelial nitric oxide synthase activity. Amelioration of these abnormalities can be achieved through Elovl6 deficiency.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2022)
Review
Pharmacology & Pharmacy
Takashi Matsuzaka, Hitoshi Shimano
Summary: The increasing prevalence of obesity worldwide has led to a dramatic increase in obesity-related diseases, including type 2 diabetes. This review suggests that manipulating the fatty acid composition through blocking Elovl6 could potentially protect against insulin resistance, impaired insulin secretion, and obesity-related disorders.
YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN
(2022)
Article
Endocrinology & Metabolism
Chika Horikawa, Kinsuke Tsuda, Yoshiharu Oshida, Jo Satoh, Yasuaki Hayashino, Naoko Tajima, Rimei Nishimura, Hirohito Sone
Summary: This study aimed to examine the dietary intake and physical activity status of Japanese patients with type 2 diabetes. The study found that patients had higher carbohydrate and lower fat consumption compared to previous studies, and a portion of patients did not have exercise habits.
DIABETOLOGY INTERNATIONAL
(2022)
Article
Nutrition & Dietetics
Yasunari Yamada, Hodaka Saito, Masaya Araki, Yuhei Tsuchimoto, Shin-ichi Muroi, Kyohei Suzuki, Kazufumi Toume, Jun-Dal Kim, Takashi Matsuzaka, Hirohito Sone, Hitoshi Shimano, Yoshimi Nakagawa
Summary: In this study, Scutellaria baicalensis root extract and wogonin were identified as activators of Fgf21 expression, which can improve metabolic diseases. ATF4 plays a critical role in wogonin's mode of action.
Article
Endocrinology & Metabolism
Rikako Nakajima, Motohiro Sekiya, Yasuhisa Furuta, Takafumi Miyamoto, Masashi Sato, Kuniaki Fukuda, Keiichiro Hattori, Yasuhito Suehara, Mamiko Sakata-Yanagimoto, Shigeru Chiba, Yuka Okajima, Takashi Matsuzaka, Satoru Takase, Mikio Takanashi, Hiroaki Okazaki, Yusuke Takashima, Mikiko Yuhara, Yuta Mitani, Nako Matsumoto, Yuki Murayama, Mariko Ohyama Osawa, Nami Ohuchi, Daichi Yamazaki, Sayuri Mori, Yoko Sugano, Yoshinori Osaki, Hitoshi Iwasaki, Hiroaki Suzuki, Hitoshi Shimano
Summary: In this study, we describe a case of a 47-year-old Japanese woman with inheritable NASH and severe dyslipidemia. Treatment with an SGLT2 inhibitor improved the progression of NASH. Whole-exome sequencing revealed mutations in PNPLA3, LGALS3, PEMT, and GCKR that may contribute to NASH and dyslipidemia. Additionally, a novel M188fs mutation in MUL1 was associated with mitochondrial dysfunction.
ENDOCRINOLOGY DIABETES AND METABOLISM CASE REPORTS
(2022)
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.
Article
Endocrinology & Metabolism
Motohiro Sekiya, Mikiko Yuhara, Yuki Murayama, Mariko Ohyama Osawa, Rikako Nakajima, Nami Ohuchi, Nako Matsumoto, Daichi Yamazaki, Sayuri Mori, Takaaki Matsuda, Yoko Sugano, Yoshinori Osaki, Hitoshi Iwasaki, Hiroaki Suzuki, Hitoshi Shimano
Summary: This article describes a 33-year-old Japanese woman with congenital aniridia and uncontrolled diabetes. A heterozygous Gln135* mutation in the PAX6 gene was identified, which may be causally associated with both congenital aniridia and diabetes. This finding supports including PAX6 in the list of genes responsible for monogenic diabetes and highlights the need to monitor blood glucose levels in patients with congenital aniridia.
ENDOCRINOLOGY DIABETES AND METABOLISM CASE REPORTS
(2022)
