Article
Pharmacology & Pharmacy
Hiroki Hashizume, Tatsuki Fukami, Kanji Mishima, Hiroshi Arakawa, Kenji Mishiro, Yongjie Zhang, Masataka Nakano, Miki Nakajima
Summary: This study aimed to clarify the human ACS isoforms responsible for CoA-conjugation of NSAIDs by considering the hepatic expression levels of ACS isoforms. Among the 10 types of NSAIDs studied, propionic acid-class NSAIDs were found to be conjugated with CoA in the human liver, while NSAIDs in other classes did not exhibit this reaction. ACSL1 was identified as the most highly expressed ACS isoform in the human liver, and could catalyze the CoA conjugation of propionic acid-class NSAIDs, which may lead to toxicity through protein adduct formation.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Hiroshi Kuwata, Eriko Nakatani, Yuki Tomitsuka, Tsubasa Ochiai, Yuka Sasaki, Emiko Yoda, Shuntaro Hara
Summary: The deficiency of ACSL4 increases susceptibility to endotoxin, possibly by overproduction of cyclooxygenase-derived eicosanoids.
Article
Biology
Yu Meng, Cheryl Ingram-Smith, Oly Ahmed, Kerry Smith
Summary: By investigating the roles of active site residues in CoA binding in acetyl-CoA synthetase (Acs) and a medium-chain acyl-CoA synthetase (Macs), it was found that certain residues play a critical role in CoA binding and catalysis, revealing the active site architecture of this important enzyme superfamily.
Article
Biochemistry & Molecular Biology
Runyi Huang, Wenli Yu, Rongzhen Zhang, Yan Xu
Summary: This study developed an efficient method for producing malonyl-CoA by screening the ACS gene from Streptomyces sp. The newly characterized ACS enzyme showed high conversion rate and yield of malonyl-CoA under optimized conditions.
PROCESS BIOCHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Mengmeng Zheng, Jun Zhang, Wan Zhang, Lu Yang, Xiaoli Yan, Wenya Tian, Zhihao Liu, Zhi Lin, Zixin Deng, Xudong Qu
Summary: In this study, an ACS enzyme was improved through protein engineering, leading to enhanced activity in synthesizing acyl-CoAs. By combining it with carboxylases, several novel antimycin analogues were successfully produced through a modified biosynthetic pathway. This study expands the catalytic mode of ACSs and provides an important tool for the biosynthesis of acyl-CoA-derived natural products.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Endocrinology & Metabolism
Lili Zhang, Kazanna C. Hames, Michael D. Jensen
Summary: This study showed that differences in enzyme activity in adipose tissue may influence direct fatty acid storage, and physically active adults have lower rates of FFA storage.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2021)
Article
Oncology
Hongzhi Li, Xiang Li, Shanshan Yu, Yanling Hu, Licheng Xu, Tianhe Wang, Xiaohong Yang, Xinyi Sun, Binghai Zhao
Summary: NAFLD is the most common liver disease globally, especially in developing countries. Hepatic MicroRNAs have been found to play a crucial role in NAFLD by controlling lipid metabolism, inflammation, and fibrosis. This study discovered that MicroRNA-23b may regulate lipid metabolism in NAFLD through its interaction with Acot4.
EXPERIMENTAL CELL RESEARCH
(2021)
Article
Biotechnology & Applied Microbiology
Masato Ikeda, Keisuke Takahashi, Tatsunori Ohtake, Ryosuke Imoto, Haruka Kawakami, Mikiro Hayashi, Seiki Takeno
Summary: Recent research found a unique mechanism of lipid homeostasis in Corynebacterium glutamicum, involving a futile cycle of acyl-CoA hydrolysis and resynthesis mediated by acyl-CoA thioesterase (Tes) and acyl-CoA synthetase (FadD). Engineering this cycle in a high-fatty-acid producer significantly increases production, offering a useful strategy for improving fatty acid production in this industrially important microorganism.
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yongjie Ma, Junyi Zha, XiangKun Yang, Qianjin Li, Qingfu Zhang, Amelia Yin, Zanna Beharry, Hanwen Huang, Jiaoti Huang, Michael Bartlett, Kaixiong Ye, Hang Yin, Houjian Cai
Summary: The study revealed that ACSL1 is highly expressed in prostate tumors, promoting the generation of fatty acyl-CoAs and facilitating cancer cell growth. ACSL1 modulates mitochondrial respiration, beta-oxidation, and ATP production, impacting fatty acid metabolism and prostate cancer progression.
Article
Biochemistry & Molecular Biology
Ravi R. Sonani, Artur Blat, Grzegorz Dubin
Summary: This study solved the crystal structures of human ACOX1a, revealing its homodimeric form and the binding of two FAD molecules at the active site. It also found that the substrate binding cleft of ACOX1a is wider compared to other fatty acid oxidation enzymes. Furthermore, the study analyzed the impact of mutations causing dysfunctionality of ACOX1a on its structure and function.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Biochemistry & Molecular Biology
Yuki Tomitsuka, Hiroki Imaeda, Haruka Ito, Isaki Asou, Masayuki Ohbayashi, Fumihiro Ishikawa, Hiroshi Kuwata, Shuntaro Hara
Summary: Long-chain acyl-CoA synthetase 4 (ACSL4) converts polyunsaturated fatty acids (PUFAs) into their acyl-CoAs and plays a crucial role in maintaining PUFA-containing membrane phospholipids. In this study, ACSL4 deficiency was found to attenuate pulmonary toxic chemical-induced lung injury and reduce mortality in mice. The results also showed that ACSL4 deficiency suppressed inflammation and neutrophil migration, as well as lipid peroxidation in the lung.
Article
Fisheries
Fang Chen, Xiaoping Huang, Hangbo Zhu, Yuanyou Li, Chao Xu, Dizhi Xie
Summary: This study investigated the molecular characterization and expression analysis of the acsl6 gene in the marine fish golden pompano (Trachinotus ovatus). The results showed that acsl6 is involved in the enrichment of DHA and over-expression of acsl6 can increase cellular DHA contents.
Article
Cell Biology
Olivia A. Maguire, Sarah E. Ackerman, Sarah K. Szwed, Aarthi V. Maganti, Francois Marchildon, Xiaojing Huang, Daniel J. Kramer, Adriana Rosas-Villegas, Rebecca G. Gelfer, Lauren E. Turner, Victor Ceballos, Asal Hejazi, Bozena Samborska, Janane F. Rahbani, Christien B. Dykstra, Matthew G. Annis, Ji-Dung Luo, Thomas S. Carroll, Caroline S. Jiang, Andrew J. Dannenberg, Peter M. Siegel, Sarah A. Tersey, Raghavendra G. Mirmira, Lawrence Kazak, Paul Cohen
Summary: The study identified the key role of crosstalk between mammary adipocytes and neoplastic cells in promoting obesity-driven breast cancer progression. Glycine amidinotransferase (Gatm) in adipocytes and Acsbg1 in cancer cells were found to be crucial for this process.
Article
Oncology
Zhihao Jia, Xiyue Chen, Jingjuan Chen, Lijia Zhang, Stephanie N. Oprescu, Nanjian Luo, Yan Xiong, Feng Yue, Shihuan Kuang
Summary: This study identifies ACSS3 as the key enzyme for propionate metabolism and demonstrates that accumulation of propionate promotes obesity and Type 2 diabetes through triggering adipocyte autophagy.
CLINICAL AND TRANSLATIONAL MEDICINE
(2022)
Review
Pharmacology & Pharmacy
Jun Hou, Changqing Jiang, Xudong Wen, Chengming Li, Shiqiang Xiong, Tian Yue, Pan Long, Jianyou Shi, Zhen Zhang
Summary: Cancer is a major global health problem, and ACSL4 has different roles in different cancer cells, both inhibiting cancer cell progression and potentially being associated with tumor cell proliferation, migration, and invasion.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Endocrinology & Metabolism
Alexi Vasbinder, Elizabeth Anderson, Husam Shadid, Hanna Berlin, Michael Pan, Tariq U. Azam, Ibrahim Khaleel, Kishan Padalia, Chelsea Meloche, Patrick O'Hayer, Erinleigh Michaud, Tonimarie Catalan, Rafey Feroze, Pennelope Blakely, Christopher Launius, Yiyuan Huang, Lili Zhao, Lynn Ang, Monica Mikhael, Kara Mizokami-Stout, Subramaniam Pennathur, Matthias Kretzler, Sven H. Loosen, Athanasios Chalkias, Frank Tacke, Evangelos J. Giamarellos-Bourboulis, Jochen Reiser, Jesper Eugen-Olsen, Eva L. Feldman, Rodica Pop-Busui, Salim S. Hayek
Summary: Diabetes mellitus is a major risk factor for severe COVID-19, and the association between diabetes and COVID-19 outcomes may be largely mediated by inflammation as assessed by suPAR levels. Hyperglycemia, independent of inflammation, also plays a role in COVID-19 outcomes.
Review
Urology & Nephrology
Judy Baek, Chenchen He, Farsad Afshinnia, George Michailidis, Subramaniam Pennathur
Summary: Dyslipidaemia is a hallmark of chronic kidney disease (CKD), with insights from lipidomics studies suggesting that alterations in free fatty acid partitioning may contribute to CKD progression.
NATURE REVIEWS NEPHROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Anindita Ravindran, Danthasinghe Waduge Badrajee Piyarathna, Jie Gohlke, Vasanta Putluri, Tanu Soni, Stacy Lloyd, Patricia Castro, Subramaniam Pennathur, Jeffrey A. Jones, Michael Ittmann, Nagireddy Putluri, George Michailidis, Thekkelnaycke M. Rajendiran, Arun Sreekumar
Summary: African-American men are more likely to die of prostate cancer than European American men. This study reveals the association between lipid metabolic pathway alterations and prostate cancer disparities, as well as specific lipid changes associated with early biochemical recurrence.
Article
Endocrinology & Metabolism
Christine P. Limonte, Erkka Valo, Viktor Drel, Loki Natarajan, Manjula Darshi, Carol Forsblom, Clark M. Henderson, Andrew N. Hoofnagle, Wenjun Ju, Matthias Kretzler, Daniel Montemayor, Viji Nair, Robert G. Nelson, John F. O'Toole, Robert D. Toto, Sylvia E. Rosas, John Ruzinski, Niina Sandholm, Insa M. Schmidt, Tomas Vaisar, Sushrut S. Waikar, Jing Zhang, Peter Rossing, Tarunveer S. Ahluwalia, Per-Henrik Groop, Subramaniam Pennathur, Janet K. Snell-Bergeon, Tina Costacou, Trevor J. Orchard, Kumar Sharma, Ian H. de Boer
Summary: The objective of this study was to understand the mechanisms underlying rapid eGFR decline in T1D patients. The researchers discovered that the urinary protein cathepsin D was associated with eGFR decline and could reflect tubulointerstitial injury in the kidneys.
Article
Multidisciplinary Sciences
Joonsang Lee, Elisa Warner, Salma Shaikhouni, Markus Bitzer, Matthias Kretzler, Debbie Gipson, Subramaniam Pennathur, Keith Bellovich, Zeenat Bhat, Crystal Gadegbeku, Susan Massengill, Kalyani Perumal, Jharna Saha, Yingbao Yang, Jinghui Luo, Xin Zhang, Laura Mariani, Jeffrey B. Hodgin, Arvind Rao
Summary: Pathologists use visual classification to assess kidney biopsy samples, but current methods lack reproducibility. To overcome this, we developed an unsupervised bag-of-words model and successfully predicted kidney function levels in chronic kidney disease patients. Our study ranked important morphological features as diagnostic markers for kidney disease.
SCIENTIFIC REPORTS
(2022)
Article
Endocrinology & Metabolism
Hetal S. Shah, Lorena Ortega Moreno, Mario Luca Morieri, Yaling Tang, Christine Mendonca, Jenny Marie Jobe, Jonathan B. Thacker, Joanna Mitri, Stefano Monti, Monika A. Niewczas, Subramaniam Pennathur, Alessandro Doria
Summary: This study aims to identify novel biomarkers of cardiovascular disease (CVD) risk in type 2 diabetes (T2D) patients through a hypothesis-free global metabolomics study, considering renal function as an important confounder. The results show that serum orotidine is a potential biomarker for increased CVD risk in T2D patients, independent of renal function. Additionally, orotidine may mediate the association between declining kidney function and CVD risk in T2D patients and could help improve CVD risk prediction.
Article
Clinical Neurology
Farsad Afshinnia, Evan L. Reynolds, Thekkelnaycke M. Rajendiran, Tanu Soni, Jaeman Byun, Masha G. Savelieff, Helen C. Looker, Robert G. Nelson, George Michailidis, Brian C. Callaghan, Subramaniam Pennathur, Eva L. Feldman
Summary: This study found that differences in serum lipidomic profiles were associated with neuropathy in type 2 diabetes. Changes in abundance of medium-chain acylcarnitines and total free fatty acids, as well as phosphatidylcholines and lysophosphatidylcholines, were observed 10 years prior to the development of neuropathy. These findings suggest that lipid profiles early in the disease course may be useful in identifying individuals at risk for neuropathy in type 2 diabetes.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Pradeep Kayampilly, Nancy Roeser, Thekkelnaycke M. Rajendiran, Subramaniam Pennathur, Farsad Afshinnia
Summary: The study showed that high glucose concentration increases de novo lipogenesis (DNL) in podocytes and tubular epithelial cells, while ACC inhibition can effectively halt or mitigate this upregulation, and reduce the expression of fibrosis and apoptosis markers. ACC inhibition is identified as a potential therapeutic target to alleviate or halt hyperglycemia-induced upregulation of DNL in podocytes and tubular cells.
Article
Endocrinology & Metabolism
Cheng-Chieh Hsu, Trevor P. Fidler, Jenny E. Kanter, Vishal Kothari, Farah Kramer, Jingjing Tang, Alan R. Tall, Karin E. Bornfeldt
Summary: Serumapolipoprotein C3 (APOC3) predicts cardiovascular events in type 1 diabetes and silencing APOC3 can prevent lesion formation and necrotic core expansion in a mouse model. Lipid-free APOC3 activates inflammasome pathway in monocytes. Hematopoietic inflammasome pathways, particularly AIM2 and NLRP3, contribute to atherosclerosis in type 1 diabetes. Necrotic core expansion in diabetes is independent of macrophage pyroptosis.
Review
Hematology
Cheng-Chieh Hsu, Jenny E. Kanter, Vishal Kothari, Karin E. . Bornfeldt
Summary: APOA1 and APOB are structural proteins of different types of lipoproteins, regulating the levels of triglyceride and cholesterol. Among the smaller APOCs, APOC3 has been studied extensively and is associated with cardiovascular and kidney diseases in type 1 diabetes. Insulin deficiency and resistance are related to elevated APOC3 levels. APOC3 slows down the clearance of triglyceride-rich lipoproteins, leading to the accumulation of atherogenic remnants in atherosclerosis lesions. Little is known about the roles of APOC1, APOC2, and APOC4 in diabetes.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2023)
Article
Environmental Sciences
Seonyoung Park, Amber L. Cathey, Wei Hao, Lixia Zeng, Subramaniam Pennathur, Max T. Aung, Zaira Rosario-Pabon, Carmen M. Velez-Vega, Jose F. Cordero, Akram Alshawabkeh, Deborah J. Watkins, John D. Meeker
Summary: The study found that gestational exposure to phthalates, a type of plasticizer, may lead to preeclampsia and preterm birth through pathways such as endocrine disruption, oxidative stress, and inflammation. The researchers investigated the associations between urinary phthalates and their mixtures with plasma eicosanoid levels during pregnancy. In both single-pollutant analysis and mixture analysis, associations with certain phthalate metabolites were found, indicating the complexity of the physiological impacts of phthalate exposure.
ENVIRONMENT INTERNATIONAL
(2023)
Article
Environmental Sciences
S. V. Thangaraj, L. Zeng, S. Pennathur, R. Lea, K. D. Sinclair, M. Bellingham, N. P. Evans, R. Auchus, V. Padmanabhan
Summary: This study investigates the impact of exposure to environmental chemicals (ECs) derived from human waste on the maternal steroid, cytokine, and oxidative stress environments. The results show that exposure to biosolids disrupts these environments and may contribute to reproductive and metabolic disruptions in offspring. This research is important for understanding the effects of ECs on pregnant individuals and their babies.
SCIENCE OF THE TOTAL ENVIRONMENT
(2023)
Article
Medicine, Research & Experimental
Madathilparambil Suresh, Sinan Aktay, George Yalamanchili, Sumeet Solanki, Dily Thazhath Sathyarajan, Manikanta Swamy Arnipalli, Subramaniam Pennathur, Krishnan Raghavendran
Summary: Research findings indicate that hypoxia from lung injury following trauma is regulated by hypoxia-inducible factor 1 alpha (HIF-1 alpha), driving the acute inflammatory response in airway epithelial cells (AEC). Metabolomics profiling reveals increased glycolytic and TCA intermediates in Type II AEC after lung contusion, while succinate directly promotes inflammation in human small AEC.
Article
Biochemistry & Molecular Biology
Stephanie A. Eid, Phillipe D. O'Brien, Katharina H. Kretzler, Dae-Gyu Jang, Faye E. Mendelson, John M. Hayes, Andrew Carter, Hongyu Zhang, Subramaniam Pennathur, Frank C. C. Brosius III, Emily J. Koubek, Eva L. Feldman
Summary: Patients with type 2 diabetes often develop microvascular complications, including diabetic kidney disease and diabetic peripheral neuropathy. This study compared the effects of three dietary interventions on a type 2 diabetes mouse model and found that they improved weight and glycemic status and alleviated diabetic kidney disease, but did not impact diabetic peripheral neuropathy. Additionally, diets that decrease fat mass may be a promising non-pharmacological approach to improve diabetic peripheral neuropathy in type 2 diabetes.
Review
Physiology
Markus Bitzer, Wenjun Ju, Lalita Subramanian, Jonathan P. Troost, Joseph Tychewicz, Becky Steck, Roger C. Wiggins, Debbie S. Gipson, Crystal A. Gadegbeku, Frank C. Brosius III, Matthias Kretzler, Subramaniam Pennathur
Summary: The research on kidney diseases is changing due to the rapid growth and advancements in omics technologies. However, the analysis, integration, and interpretation of big data have been a challenge in using these technologies. To address this issue, the University of Michigan's MKTC has established the Applied Systems Biology Core to provide support and services for the global kidney research community.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2022)