Article
Neurosciences
Nathan C. Winn, Elysa M. Wolf, Jamie N. Garcia, Alyssa H. Hasty
Summary: This study shows that loss of Trem2 does not worsen metabolic dysfunction in obese mice, indicating a dissociation between adipose tissue remodeling caused by Trem2 loss and whole-body metabolic homeostasis.
JOURNAL OF PHYSIOLOGY-LONDON
(2022)
Article
Biochemistry & Molecular Biology
Jain Jeong, Soyoung Jang, Song Park, Wookbong Kwon, Si-Yong Kim, Soyoen Jang, Jiwon Ko, Si Jun Park, Su-geun Lim, Duhak Yoon, Junkoo Yi, Sanggyu Lee, Myoung Ok Kim, Seong-Kyoon Choi, Zae Young Ryoo
Summary: The study highlighted the important role of JAZF1 in adipocyte differentiation and related metabolism through experiments in vitro and in vivo. Heterozygous JAZF1 knockout mice exhibited abnormalities in adipose tissue mass and glucose metabolism, providing new insights for treating obesity and metabolic disorders.
CELL AND BIOSCIENCE
(2021)
Article
Endocrinology & Metabolism
Gabriela Ramirez-Hernandez, Elva Adan-Castro, Nundehui Diaz-Lezama, Xarubet Ruiz-Herrera, Gonzalo Martinez de la Escalera, Yazmin Macotela, Carmen Clapp
Summary: Prolactin (PRL) levels are reduced in rats with diabetes or obesity, and lower PRL circulating levels correlate with increased prevalence of diabetes and higher risk of metabolic alterations. PRL stimulates beta-cell proliferation, survival, and insulin production, and lack of PRL signaling results in decreased insulin release and pancreatic inflammation. PRL protects whole body glucose homeostasis by reducing beta-cell loss and alleviating pancreatic inflammation, potentially proving beneficial in diabetes.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ming-Fo Hsu, Yoshihiro Ito, Maryam Afkarian, Fawaz G. Haj
Summary: Shp2 contributes significantly to podocyte function under hyperglycemia, and its deficiency can protect podocyte function from high glucose damage. Its deficiency alters insulin signaling and reduces hyperglycemia-induced endoplasmic reticulum stress, inflammation, and fibrosis.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Editorial Material
Neurosciences
Nathan C. Winn, Elysa M. Wolf, Jamie N. Garcia, Alyssa H. Hasty
Summary: Trem2, highly expressed on myeloid cells, is involved in lipid homeostasis and inflammation. This study aimed to determine the causal role of Trem2 in regulating glucose homeostasis and insulin sensitivity in mice.
JOURNAL OF PHYSIOLOGY-LONDON
(2022)
Article
Pharmacology & Pharmacy
Yi Zhang, Binhao Cai, Yingying Li, Ying Xu, Yuhan Wang, Lulu Zheng, Xiaochun Zheng, Lina Yin, Gaozhi Chen, Yunxiang Wang, Guang Liang, Lingfeng Chen
Summary: Liver fibrosis is characterized by the activation of hepatic stellate cells (HSCs) and matrix deposition. The oncogenic protein tyrosine phosphatase Src homology 2 domain-containing phosphatase 2 (SHP2) is a potential therapeutic target for fibrosis. In this study, a furanogermacrane sesquiterpene, linderalactone (LIN), was identified as a novel SHP2 inhibitor that significantly inhibits SHP2 dephosphorylation activity. In vivo administration of LIN ameliorated HSC activation and liver fibrosis by inhibiting the TGF beta/Smad3 pathway.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Caroline C. Duwaerts, Kevin Siao, Russell K. Soon, Chris Her, Takao Iwawaki, Kenji Kohno, Aras N. Mattis, Jacquelyn J. Maher
Summary: The transcription factor X-box binding protein-1 (XBP1) plays a central role in controlling cellular responses to endoplasmic reticulum stress. Genetic deletion of XBP1 in adult mouse liver led to acute liver injury in response to fructose challenge, primarily due to hyperactivation of IRE1 alpha. Further exploration of IRE1 alpha as a contributor to liver diseases is supported by these findings.
CELL DEATH AND DIFFERENTIATION
(2021)
Article
Nutrition & Dietetics
Zhitian Lu, Xudong Li, Min Wang, Xiaojun Zhang, Runxuan Zhuang, Fan Wu, Wenxue Li, Wei Zhu, Bo Zhang
Summary: Nobiletin (NOB), a compound found in citrus peels, has potential lipid-lowering and circadian-enhancing properties. This study showed that NOB can reduce liver triglyceride levels and regulate genes involved in lipid and cholesterol metabolism, independently of the core clock component Bmal1.
Article
Medicine, Research & Experimental
Min-Hyun Kim, Yuan Li, Qiantao Zheng, Lin Jiang, Martin G. Myers Junior, Wen-Shu Wu, Liangyou Rui
Summary: A neuronal Slug/epigenetic reprogramming/leptin resistance axis was discovered, which promotes energy imbalance, obesity, and metabolic disease. Slug represses LepRb expression by binding to and inhibiting LepRb promoter, leading to obesity and metabolic disorders.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Endocrinology & Metabolism
Marine L. Croze, Arthur Guillaume, Melanie Ethier, Grace Fergusson, Caroline Tremblay, Scott A. Campbell, Hasna Maachi, Julien Ghislain, Vincent Poitout
Summary: Activation of both GPR120 and GPR40 enhances insulin secretion in isolated islets, but combined deletion of these receptors has minimal effects on glucose homeostasis in vivo in mice.
Article
Biochemistry & Molecular Biology
Liangkui Li, Haoyu Zhou, Jinhui Wang, Jiaxin Li, Xuchao Lyu, Wenshan Wang, Chengting Luo, He Huang, Dawang Zhou, Xiaowei Chen, Li Xu, Peng Li
Summary: This study reveals that the liver functions as an energy conversion center to maintain blood glucose homeostasis in neonates. Glucose is found to be the universal fuel essential for neonatal life. The limitation of lipid supply in milk leads to severe hypoglycemia and neonatal lethality.
JOURNAL OF LIPID RESEARCH
(2023)
Article
Nutrition & Dietetics
E. Matthew Morris, Roberto D. Noland, Michael E. Ponte, Michelle L. Montonye, Julie A. Christianson, John A. Stanford, John M. Miles, Matthew R. Hayes, John P. Thyfault
Summary: The study suggests that reduced liver energy metabolism may contribute to diet-induced weight gain, with potential sex-specific effects, and indicates a role for vagal signaling in short-term diet-induced weight gain.
Article
Multidisciplinary Sciences
Weiting Zhong, Mingming Ma, Jingwen Xie, Chengcui Huang, Xiaoyan Li, Min Gao
Summary: The activation of TRPM7 is crucial in regulating pro-inflammatory responses in adipocytes, and its deficiency or inhibition can alleviate adipose tissue inflammation, improve glucose homeostasis, and suppress weight gain in obese mice.
NATURE COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Katrin Panzitt, Martin Wagner
Summary: The liver serves as a central metabolic hub that coordinates nutritional inputs and metabolic outputs. FXR in the liver and intestine plays a crucial role in regulating postprandial nutrient disposal. Aside from classical roles, FXR also has effects on amino acid, protein metabolism, autophagic turnover, and inflammation, which are less studied. Additionally, understanding of how FXR signaling is affected by posttranslational modifications and different isoforms is important for potential pharmaceutical targeting in clinical applications.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Natalie R. Janzen, Jamie Whitfield, Lisa Murray-Segal, Bruce E. Kemp, John A. Hawley, Nolan J. Hoffman
Summary: By studying AMPK beta double knock-in mice, it was found that DKI mice displayed increased whole-body fat mass and glucose intolerance, along with reduced fat oxidation compared to wild-type. DKI mice had reduced liver glycogen content in the fed state, increased utilization of skeletal muscle glycogen in response to fasting but no repletion during refeeding, and also showed reductions in AMPK protein content in liver and skeletal muscle compared to WT.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Kaja Plucinska, Nimesh Mody, Ruta Dekeryte, Kirsty Shearer, George D. Mcilroy, Mirela Delibegovic, Bettina Platt
Summary: This study assessed the effects of high-fat diet on the metabolic and cognitive phenotypes in diabetic BACE1 knock-in mice and found that high-fat diet worsened metabolism and induced early mortality in these mice. Furthermore, it exacerbated spatial memory deficits in Alzheimer's-like BACE1 mice. However, these effects were partially prevented by Fenretinide treatment.
NUTRITIONAL NEUROSCIENCE
(2022)
Article
Cardiac & Cardiovascular Systems
Nadine Godsman, Michael Kohlhaas, Alexander Nickel, Lesley Cheyne, Marco Mingarelli, Lutz Schweiger, Claire Hepburn, Chantal Munts, Andy Welch, Mirela Delibegovic, Marc Van Bilsen, Christoph Maack, Dana K. Dawson
Summary: This study investigates the specific metabolic adaptations in takotsubo patients and their implications for future therapies. The study reveals dysregulation of glucose and lipid metabolic pathways, impaired Ca2+ handling, inflammation, and upregulation of remodeling pathways in the hearts of takotsubo patients. However, the integrity of both mitochondria and cardiomyocytes is preserved.
CARDIOVASCULAR RESEARCH
(2022)
Article
Endocrinology & Metabolism
Mayumi Nagashimada, Kazuki Sawamoto, Yinhua Ni, Hironori Kitade, Naoto Nagata, Liang Xu, Masuko Kobori, Naofumi Mukaida, Tatsuya Yamashita, Shuichi Kaneko, Tsuguhito Ota
Summary: The CX3CL1-CX3CR1 system is crucial in regulating inflammation, particularly in obese mice with adipose tissue inflammation and insulin resistance. Deficiency in CX3CR1 signaling leads to an increase in M1 polarized macrophages, worsening glucose tolerance and insulin resistance in obese mice. Targeting the CX3CL1-CX3CR1 system may be beneficial in treating type 2 diabetes by modulating M1/M2 macrophages.
Article
Endocrinology & Metabolism
Liang Xu, Yongping Chen, Mayumi Nagashimada, Yinhua Ni, Fen Zhuge, Guanliang Chen, Haoran Li, Tongtong Pan, Tatsuya Yamashita, Naofumi Mukaida, Shuichi Kaneko, Tsuguhito Ota, Naoto Nagata
Summary: The study revealed that CCL3 plays a crucial role in the development of fatty liver disease by facilitating macrophage infiltration and M1 polarization, highlighting the potential therapeutic target of CCL3 in the treatment of NAFLD.
METABOLISM-CLINICAL AND EXPERIMENTAL
(2021)
Article
Endocrinology & Metabolism
Yinhua Ni, Fen Zhuge, Liyang Ni, Naoto Nagata, Tatsuya Yamashita, Naofumi Mukaida, Shuichi Kaneko, Tsuguhito Ota, Mayumi Nagashimada
Summary: This study investigates the roles of CX3CL1/CX3CR1 in macrophage migration and polarization in the livers of NASH mice. It is found that CX3CL1 and CX3CR1 expression is upregulated in NASH mice livers, and CX3CR1 is predominantly expressed by F4/80+ macrophages. CX3CR1 deficiency leads to increased inflammatory monocyte/macrophage infiltration and a shift towards M1 dominant macrophages, exacerbating NASH progression. Deletion of CCL2 in CX3CR1-deficient mice alleviates NASH progression by reducing macrophage infiltration and inducing a shift towards M2 dominant macrophages.
METABOLISM-CLINICAL AND EXPERIMENTAL
(2022)
Article
Toxicology
Zheng Jing, Hironao Okubo, Jun-ichi Morishige, Pingping Xu, Nazmul Hasan, Naoto Nagata, Hitoshi Ando
Summary: This study reveals the detrimental effects of lenvatinib on OCTN2 expression, carnitine content, and mitochondrial function in skeletal muscle which may be associated with muscle toxicity.
TOXICOLOGY LETTERS
(2022)
Article
Multidisciplinary Sciences
Takayoshi Shirasaki, Satoshi Yamagoe, Tetsuro Shimakami, Kazuhisa Murai, Ryu Imamura, Kiyo-Aki Ishii, Hiroaki Takayama, Yukako Matsumoto, Natsumi Tajima-Shirasaki, Naoto Nagata, Ryogo Shimizu, Souma Yamanaka, Atsushi Abe, Hitoshi Omura, Kazunori Kawaguchi, Hikari Okada, Taro Yamashita, Tomoki Yoshikawa, Kazuhiro Takimoto, Motoko Taharaguchi, Shogo Takatsuka, Yoshitsugu Miyazaki, Toshikatsu Tamai, Yamato Tanabe, Makoto Kurachi, Yasuhiko Yamamoto, Shuichi Kaneko, Kunio Matsumoto, Toshinari Takamura, Masao Honda
Summary: This study reveals that leukocyte cell-derived chemotaxin 2 (LECT2) promotes RIG-I-mediated innate immune response and inhibits lymphocytic choriomeningitis virus replication by preventing RIG-I degradation. It also uncovers the crosstalk between LECT2-MET and HGF-MET signaling pathways, suggesting the therapeutic potential of targeting LECT2 in infectious diseases and cancer.
NATURE COMMUNICATIONS
(2022)
Letter
Medicine, General & Internal
Nurul Nabilah Akmal Hashim, Sumaiyah Mat, Phyo Kyaw Myint, Sheng Hui Kioh, Mirela Delibegovic, Ai-Vyrn Chin, Shahrul Bahyah Kamaruzzaman, Noran Naqiah Hairi, Selina Khoo, Maw Pin Tan
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Nutrition & Dietetics
Hitoshi Ando, Naoto Nagata, Takashi Hosono, Nazmul Hasan, Jun-ichi Morishige, Takiko Daikoku, Yoshiko Maida, Masanori Ono, Tomoko Fujiwara, Hiroshi Fujiwara
Summary: This study aimed to investigate whether habitual feeding time affects the daily rhythm of core body temperature (CBT). The results showed that the effect of habitual feeding time on CBT lasts until the following day and may be mediated by both UCP1-dependent and -independent mechanisms.
FRONTIERS IN NUTRITION
(2022)
Article
Medicine, Research & Experimental
Nadine Sommer, Ahlima Roumane, Weiping Han, Mirela Delibegovic, Justin J. Rochford, George D. Mcilroy
Summary: This study suggests that gene therapy has the potential to be an effective treatment for congenital generalized lipodystrophy type 2. Using a mouse model, researchers found that systemic adeno-associated virus delivery of the BSCL2 gene could restore white adipose tissue development and improve metabolic health in adult seipin knockout mice. The findings highlight the therapeutic potential of gene therapy for correcting metabolic complications in patients with congenital lipodystrophy.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2022)
Article
Biochemistry & Molecular Biology
Sarah E. J. Kamli-Salino, Paul A. J. Brown, Timo N. Haschler, Lihuan Liang, Denis Feliers, Heather M. Wilson, Mirela Delibegovic
Summary: This study compared the effects of freshly prepared STZ and anomer-equilibrated STZ on kidney damage in mice and found that anomer-equilibrated STZ caused more severe kidney tubule structural damage, while freshly prepared STZ only caused mild changes. Therefore, anomer-equilibrated STZ provides a reliable mouse model for diabetes and early-stage diabetic nephropathy.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Annesha Sil, Marina Souza Matos, Mirela Delibegovic, Bettina Platt
Summary: Insufficiently characterised controls in biomedical research, including neuroscience and metabolism, have contributed to irreproducibility. Phenotypic differences between commonly used C57BL/6 substrains as control animals are now increasingly recognized. This study investigated metabolic characteristics in multiple C57BL/6 substrains, revealing systematic and tissue-specific differences influenced by vendor and sex, emphasizing the importance of selecting and characterising control subjects to ensure proper experimental outcomes.
Review
Medicine, General & Internal
Naoto Nagata, Guanliang Chen, Liang Xu, Hitoshi Ando
Summary: Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease, and hepatic inflammation plays a crucial role in its development. Chemokines, especially CCL2 and CCL5, are important in inducing insulin resistance, steatosis, inflammation, and fibrosis in NAFLD. Cenicriviroc (CVC), a dual antagonist of chemokine receptors, has shown potential as a therapeutic approach for NASH-associated liver fibrosis.
MEDICINA-LITHUANIA
(2022)
Review
Endocrinology & Metabolism
Stavroula Kastora, Manisha Patel, Ben Carter, Mirela Delibegovic, Phyo Kyaw Myint
Summary: This study is the first umbrella systematic review and meta-analysis to analyze the outcomes of COVID-19 infection in patients with diabetes, including mortality, ICU admission, ventilation requirement, illness severity, and discharge rate. The results show that patients with diabetes have a higher risk of COVID-19-related mortality, increased ICU admissions, and increased ventilation requirements worldwide.
ENDOCRINOLOGY DIABETES & METABOLISM
(2022)
Article
Medicine, General & Internal
Nazmul Hasan, Koki Sugimoto, Koki Yamada, Jun-ichi Morishige, Kentaro Ushijima, Akio Fujimura, Naoto Nagata, Hitoshi Ando
Summary: This study investigated whether chronic treatment with the antidiabetic agent metformin impairs circadian clocks, especially if given at an inappropriate time. The results showed that chronic treatment with metformin does not disrupt circadian clock gene expression in peripheral tissues and affects hepatic AMPK activation rhythm in diabetic mice.
MEDICINA-LITHUANIA
(2022)