Article
Biochemistry & Molecular Biology
Filiz Guclu-Geyik, Pinar Koseoglu, Gamze Guven, Gunay Can, Aysem Kaya, Neslihan Coban, Evrim Komurcu-Bayrak, Nihan Erginel-Unaltuna
Summary: This study investigated the effect of ITLN1 gene polymorphism rs2274907 on obesity and type 2 diabetes in Turkish adults. The results showed no significant association between this polymorphism and obesity, type 2 diabetes, or serum intelectin-1 level. However, it was found that the TA+AA carriers had significantly higher triglyceride levels compared to the TT carriers in obese and type 2 diabetes women.
BIOCHEMICAL GENETICS
(2023)
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
Chemistry, Medicinal
Wei Meng, Robert Brigance, James Mignone, Lidet Negash, Guohua Zhao, Saleem Ahmad, Wei Wang, Fang Moore, Xiang-Yang Ye, Jung-Hui Sun, Arvind Mathur, Yi-Xin Li, Anthony Azzara, Zhengping Ma, Ching-Hsuen Chu, Mary Jane Cullen, Suzanne Rooney, Susan Harvey, Lisa Kopcho, Lynn Abell, Kevin O'Malley, William Keim, Elizabeth A. Dierks, Shu Chang, Kimberly A. Foster, David Harden, Marta Dabros, Vineet Goti, Claudia De Oliveira, Gopal Krishna, Mary Ann Pelleymounter, Jean Whaley, Jeffrey A. Robl, Dong Cheng, Pratik Devasthale
Summary: A series of novel tetrazolone compounds with potent MGAT2 inhibitory activity and favorable in vitro profiles were discovered. These compounds showed significant reduction in food intake and body weight in mouse models. One lead compound (12, BMS-986172) exhibited on-target- and mechanism-based pharmacology in MGAT2 knockout mice, and its favorable pharmacokinetic profile suggested a low dose for achieving targeted efficacious exposures in humans. Phase 1 trial confirmed the achievement of targeted efficacious exposures at a low dose in humans, supporting compound 12 as a potential development candidate for metabolic disorders treatment.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Qianfen Wan, Carmen Calhoun, Tarik Zahr, Li Qiang
Summary: Obesity is caused by the expansion of adipose tissue, which regulates energy balance, adipokine secretion, thermogenesis, and inflammation. Adipocytes are traditionally believed to store lipids through lipid synthesis, but they can still function and respond to nutrients even when depleted of lipid droplets. This raises the question of whether lipid synthesis and storage can be separated from adipocyte development and function.
Article
Endocrinology & Metabolism
Xiaotong Li, Mengzi Sun, Yixue Yang, Nan Yao, Shoumeng Yan, Ling Wang, Wenyu Hu, Ruirui Guo, Yuxiang Wang, Bo Li
Summary: This study evaluated the association between triglyceride glucose (TyG) index and new-onset diabetes under different glycemic states and compared the predictive value of TyG-associated parameters, obesity indices, and lipid ratios. The results showed a positive and linear association between TyG index and new-onset diabetes. TyG-WHtR and TyG-BMI were effective markers for identifying the risks of diabetes.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Nutrition & Dietetics
Xinli Song, Letao Chen, Senmao Zhang, Yiping Liu, Jianhui Wei, Tingting Wang, Jiabi Qin
Summary: The study found that gestational diabetes mellitus and high maternal triglyceride levels independently increased the risk of macrosomia, and collectively acted as significant mediators in the relationship between pre-pregnancy overweight/obesity and macrosomia.
Article
Chemistry, Analytical
Jun Sun, Lei Zhang, Lingchun Zhang, Qingwang Liu
Summary: A novel UHPLC-MS/MS method was developed for the simultaneous determination of Lumiracoxib and its metabolites in rat plasma, validated according to FDA guidance, demonstrating high linearity, stability, and accuracy, suitable for pharmacokinetic studies in rats.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2021)
Article
Cardiac & Cardiovascular Systems
Qing Yang, Huichao Xu, Hongli Zhang, Yanying Li, Shuxiong Chen, Dongye He, Guangzhi Yang, Bo Ban, Mei Zhang, Fupeng Liu
Summary: This study aimed to investigate the predictive value of the TyG index for visceral obesity and body fat distribution in patients with type 2 diabetes mellitus. The results showed that the TyG index was significantly correlated with visceral adipose area, subcutaneous adipose area, and visceral adipose density, and it could be used as an independent factor for visceral obesity. In addition, the combination of the TyG index and BMI improved the prediction of visceral obesity.
CARDIOVASCULAR DIABETOLOGY
(2023)
Article
Chemistry, Applied
Shi-Zhou Qi, Ban-Ban Li, Meng-Shan Liu, Zhen Zhang, Shuang Miao, Kai-Kai Gong
Summary: In this study, a new flavonoid was isolated from the seeds of Cullen corylifolium and evaluated for its inhibitory activity against DGAT. Additionally, a summary of 45 other flavonoids and their structure-activity relationships were discussed.
NATURAL PRODUCT RESEARCH
(2023)
Article
Plant Sciences
Haiyan Ma, Xiaoying Wu, Ziwang Wei, Liang Zhao, Zhongze Li, Qing Liang, Jie Zheng, Yu Wang, Yanhua Li, Linfei Huang, Qiang Hu, Danxiang Han
Summary: The study revealed that a type of enzyme in microalgae, DGAT, may lose its original function and instead function as another enzyme, LPAAT. The HpDGTT2 identified in the experiment was found to act as a LPAAT, regulating lipid biosynthesis, which could help to elucidate the structure-function relationship of this group of enzymes.
JOURNAL OF EXPERIMENTAL BOTANY
(2021)
Article
Cardiac & Cardiovascular Systems
Christopher M. Hearon, Katrin A. Dias, James P. MacNamara, Michinari Hieda, Yogamaya Mantha, Rakushumimarika Harada, Mitchel Samels, Margot Morris, Lidia S. Szczepaniak, Benjamin D. Levine, Satyam Sarma
Summary: The study found that one year of high-intensity interval training can improve exercise capacity, cardiovascular structure/function, and adiposity in obese middle-aged adults at high-risk of heart failure (stage A), with no independent or additive effect of n-3 fatty acid supplementation.
JACC-HEART FAILURE
(2022)
Article
Biochemistry & Molecular Biology
Jose Fernando Rinaldi de Alvarenga, Mar Garcia-Aloy, Marynka Ulaszewska, Sebastian Zagmutt, Marta Perez-Montero, Urska Vrhovsek, Rosa M. Lamuela-Raventos, Rosalia Rodriguez-Rodriguez
Summary: This study investigates the impact of sofrito, a tomato and olive oil-based sauce, on energy metabolism in obese rats. The results show that sofrito intake promotes lipid oxidation, ketogenesis activation, and alters the lipidomic profile in fat depots. These findings provide further evidence for the beneficial effects of sofrito and components of the Mediterranean diet against obesity.
Article
Chemistry, Medicinal
Renshuai Zhang, Zhengming Song, Xueting Wang, Jiao Xue, Dongming Xing
Summary: A potent dual-inhibitor against pancreatic triglyceride lipase (PTL) and Niemann-Pick C1-like 1 (NPC1L1) has been identified through molecular hybridization-based one-step modification screening, named as P1-11. Compound P1-11 inhibits PTL via covalent binding with an IC50 value of 2.1 mu M, and significantly reduces cholesterol absorption in a non-competitive manner. This research supports the development of novel treatment options for obesity patients with hypercholesteremia by targeting PTL and NPC1L1 simultaneously.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Endocrinology & Metabolism
Paulina Oboza, Natalia Ogarek, Magdalena Olszanecka-Glinianowicz, Piotr Kocelak
Summary: Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by insulin deficiency. Environmental and genetic factors contribute to its development. The incidence of T1D and obesity has been increasing, particularly among young individuals. Research shows that overweight or obesity is prevalent in T1D patients and is associated with various risk factors. The coexistence of T1D and T2D, known as double or hybrid diabetes, increases the risk of complications and reduces life expectancy. This review aims to summarize the relationship between overweight/obesity and T1D.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Cell Biology
David D. Roberts, Jeffrey S. Isenberg
Summary: Thrombospondin-1 (TSP1) is a family of secreted proteins that modulate cell behavior by interacting with molecules in the extracellular matrix and cell surface receptors, with CD47 being a high-affinity receptor for TSP1. CD47 is crucial in limiting innate immune cell activities and mediating TSP1 signaling, contributing to mitochondrial, metabolic, and endocrine dysfunction. Elevated TSP1 expression, particularly through CD47, is associated with obesity, fatty liver disease, and diabetes, suggesting a potential for therapeutic intervention.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Adam G. Schwaid, Chunyan Su, Paula Loos, Jiang Wu, Chuong Nguyen, Kathryn L. Stone, Jean Kanyo, Kieran F. Geoghegan, Samit K. Bhattacharya, Robert L. Dow, Leonard Buckbinder, Philip A. Carpino
ACS CHEMICAL BIOLOGY
(2015)
Article
Chemistry, Medicinal
Mark Ammirati, Scott W. Bagley, Samit K. Bhattacharya, Leonard Buckbinder, Anthony A. Carlo, Rebecca Conrad, Christian Cortes, Robert L. Dow, Matthew S. Dowling, Ayman El-Kattan, Kristen Ford, Cristiano R. W. Guimaraes, David Hepworth, Wenhua Jiao, Jennifer LaPerle, Shenping Liu, Allyn Londregan, Paula M. Loria, Alan M. Mathiowetz, Michael Munchhoft, Suvi T. M. Orr, Donna N. Petersen, David A. Price, Athanasia Skoura, Aaron C. Smith, Jian Wang
ACS MEDICINAL CHEMISTRY LETTERS
(2015)
Article
Chemistry, Medicinal
Robert L. Dow, Mark Ammirati, Scott W. Bagley, Samit K. Bhattacharya, Leonard Buckbinder, Christian Cortes, Ayman F. El-Kattan, Kristen Ford, Gary B. Freeman, Cristiano R. W. Guimaraes, Shenping Liu, Mark Niosi, Athanasia Skoura, David Tess
JOURNAL OF MEDICINAL CHEMISTRY
(2018)
Article
Biochemistry & Molecular Biology
Robert L. Dow, Melissa P. Andrews, Jian-Cheng Li, E. Michael Gibbs, Angel Guzman-Perez, Jennifer L. LaPerle, Qifang Li, Dawn Mather, Michael J. Munchhof, Mark Niosi, Leena Patel, Christian Perreault, Susan Tapley, William J. Zavadoski
BIOORGANIC & MEDICINAL CHEMISTRY
(2013)
Article
Chemistry, Medicinal
Robert L. Dow, Melissa Andrews, Gary E. Aspnes, Gayatri Balan, E. Michael Gibbs, Angel Guzman-Perez, Kapil Karki, Jennifer L. LaPerle, Jian-Cheng Li, John Litchfield, Michael J. Munchhof, Christian Perreault, Leena Patel
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2011)
Article
Chemistry, Medicinal
Kevin J. Filipski, Angel Guzman-Perez, Jianwei Bian, Christian Perreault, Gary E. Aspnes, Mary T. Didiuk, Robert L. Dow, Richard F. Hank, Christopher S. Jones, Robert J. Maguire, Meihua Tu, Dongxiang Zeng, Shenping Liu, John D. Knafels, John Litchfield, Karen Atkinson, David R. Derksen, Francis Bourbonais, Ketan S. Gajiwala, Michael Hickey, Theodore O. Johnson, Paul S. Humphries, Jeffrey A. Pfefferkorn
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2013)
Article
Chemistry, Medicinal
Srinivas R. Chirapu, Jonathan N. Bauman, Heather Eng, Theunis C. Goosen, Timothy J. Strelevitz, Subhash C. Sinha, Robert L. Dow, M. G. Finn
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2014)
Review
Chemistry, Medicinal
Meihua Tu, Alan M. Mathiowetz, Jeffrey A. Pfefferkorn, Kimberly O. Cameron, Robert L. Dow, John Litchfield, Li Di, Bo Feng, Spiros Liras
CURRENT TOPICS IN MEDICINAL CHEMISTRY
(2013)
Review
Chemistry, Medicinal
Srinivas Reddy Chirapu, Charles J. Rotter, Emily L. Miller, Manthena V. Varma, Robert L. Dow, M. G. Finn
CURRENT TOPICS IN MEDICINAL CHEMISTRY
(2013)
Article
Chemistry, Medicinal
David A. Griffith, Robert L. Dow, Kim Huard, David J. Edmonds, Scott W. Bagley, Jana Polivkova, Dongxiang Zeng, Carmen N. Garcia-Irizarry, James A. Southers, William Esler, Paul Amor, Kathrine Loomis, Kirk McPherson, Kevin B. Bahnck, Cathy Preville, Tereece Banks, Dianna E. Moore, Alan M. Mathiowetz, Elnaz Menhaji-Klotz, Aaron C. Smith, Shawn D. Doran, David A. Beebe, Matthew F. Dunn
JOURNAL OF MEDICINAL CHEMISTRY
(2013)
Article
Chemistry, Organic
Kim Huard, Scott W. Bagley, Elnaz Menhaji-Klotz, Cathy Preville, James A. Southers, Aaron C. Smith, David J. Edmonds, John C. Lucas, Matthew F. Dunn, Nigel M. Allanson, Emma L. Blaney, Carmen N. Garcia-Irizarry, Jeffrey T. Kohrt, David A. Griffith, Robert L. Dow
JOURNAL OF ORGANIC CHEMISTRY
(2012)
Article
Chemistry, Organic
Kevin B. Bahnck, Andrei Shavnya, Yong Tao, Susan C. Lilley, Melissa P. Andrews, Gary E. Aspnes, David J. Bernhardson, David R. Bill, Mark W. Bundesmann, Robert L. Dow, Kapil Karki, Tung Le, Qifang Li, Michael J. Munchhof, Asaad Nematalla, Mohammed Nihlawi, Leena Patel, Christian Perreault, Michael Waldo
SYNTHESIS-STUTTGART
(2012)
Article
Chemistry, Medicinal
Robert L. Dow, Philip A. Carpino, Denise Gautreau, John R. Hadcock, Philip A. Iredale, Dawn Kelly-Sullivan, Jeffrey S. Lizano, Rebecca E. O'Connor, Steven R. Schneider, Dennis O. Scott, Karen M. Ward
ACS MEDICINAL CHEMISTRY LETTERS
(2012)
Article
Chemistry, Medicinal
Kim Huard, Aaron C. Smith, Gregg Cappon, Robert L. Dow, David J. Edmonds, Ayman El-Kattan, William P. Esler, Dilinie P. Fernando, David A. Griffith, Amit S. Kalgutkar, Trenton T. Ross, Scott W. Bagley, David Beebe, Yi-An Bi, Shawn Cabral, Collin Crowley, Shawn D. Doran, Matthew S. Dowling, Spiros Liras, Vincent Mascitti, Mark Niosi, Jeffrey A. Pfefferkorn, Jana Polivkova, Cathy Preville, David A. Price, Andre Shavnya, Norimitsu Shirai, Andrew H. Smith, James R. Southers, David A. Tess, Benjamin A. Thuma, Manthena V. Varma, Xiaojing Yang
JOURNAL OF MEDICINAL CHEMISTRY
(2020)