Review
Pharmacology & Pharmacy
Hao Chen, Lan-Lan Li, Yan Du
Summary: Liver diseases, characterized by metabolic disorder, have become a global public health problem with high morbidity and mortality. Kruppel-like factor 15 (KLF15), a zinc-finger transcription factor mainly enriched in liver, is rapidly activated during fasting and regulates various metabolic processes in the liver. This review summarizes the latest advances of KLF15 in metabolic reprogramming and its role in acute liver injury, hepatitis B virus, and autoimmune hepatitis, aiming to assess the potential of KLF15 as a therapeutic target and prognostic biomarker for liver diseases.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Xiaoyan Chen, Wenjie Shi, Yong Xie, Yunwu Wang, Qian Yao, Huajing Ke, Xuan Xu, Hui Liu, Pi Liu, Xiaojiang Zhou
Summary: This study investigated the role of Kruppel-like factor 14 (KLF14) in hepatic lipid metabolism and its mechanism in nonalcoholic steatohepatitis (NASH). The expression of KLF14 was found to be decreased in NASH patients and mice fed a high-fat diet. Overexpression of KLF14 alleviated lipid accumulation and oxidative stress in the mouse model of NASH through the activation of the PPARa pathway.
Article
Biochemistry & Molecular Biology
Xiaoyan Chen, Wenjie Shi, Yong Xie, Yunwu Wang, Qian Yao, Huajing Ke, Xuan Xu, Hui Liu, Pi Liu, Xiaojiang Zhou
Summary: This study investigates the role of Kruppel-like factor 14 (KLF14) in hepatic lipid metabolism in nonalcoholic steatohepatitis (NASH). The expression of KLF14 was found to be decreased in NASH patients and mice fed a high-fat diet. Knockdown of KLF14 promoted the progression of hepatic steatosis by downregulating fatty acid oxidation genes.
Review
Oncology
Esther Lee, Jacky Cheung, Agnieszka B. Bialkowska
Summary: Kruppel-like factors (KLFs) are transcription factors that regulate various biological processes and participate in disease development and progression. KLF4 and KLF5, two significant members of this family, play crucial roles in embryogenesis, differentiation, and tumorigenesis. They maintain tissue homeostasis, regulate inflammation and response to injury, and have important functions in a variety of cancers. Recent studies have provided new insights into their opposing roles and mechanisms in gene expression, cellular function, and tumorigenesis. This review will focus on the roles of KLF4 and KLF5 in colorectal cancer, which can contribute to the development of targeted cancer therapy.
Article
Chemistry, Multidisciplinary
Yu Li, Yankang Zhang, Ting Zhang, Xiaodan Ping, Dongmei Wang, Yanru Chen, Jian Yu, Caizhi Liu, Ziqi Liu, Yuhan Zheng, Yongfeng Yang, Chengchao Ruan, Dali Li, Zhenyu Du, Jiqiu Wang, Lingyan Xu, Xinran Ma
Summary: This study investigates the impact of m(6)A modification on beige fat biology. The results show that glycolytic genes undergo m(6)A modification and transcriptional activation upon beige adipocytes activation. Deficiency of Mettl3 in mature beige adipocytes leads to suppressed glycolytic capability, reduced thermogenesis, and impaired preadipocytes proliferation through lactate production. Additionally, Mettl3 and m(6)A reader Igf2bp2 control mRNA stability of key glycolytic genes in beige adipocytes.
Article
Biochemistry & Molecular Biology
Lupe Furtado-Alle, Luciane Tureck, Carolina S. de Oliveira, Joao V. M. Hortega, Ricardo L. R. Souza
Summary: Butyrylcholinesterase (BChE) is an enzyme found primarily in the liver, plasma, and brain, and it has been recognized for its role in the hydrolysis of choline esters. Recent studies have shown its involvement in lipid metabolism, suggesting it plays a crucial role in maintaining lipid homeostasis. However, the relationship between external factors and BChE activity in lipid metabolic pathways is still complex and requires further investigation.
CHEMICO-BIOLOGICAL INTERACTIONS
(2023)
Article
Agriculture, Dairy & Animal Science
Xu Zhao, Huashan Huang, Xiao Ding, Zaibin Yang, Yanru Hou, Hongfang Wang
Summary: The study showed that ANGPTL4 could promote lipolysis and inhibit lipoprotein lipase expression in broiler breast muscle.
Article
Endocrinology & Metabolism
Yuko Nabatame, Tetsuya Hosooka, Chikako Aoki, Yusei Hosokawa, Makoto Imamori, Yoshikazu Tamori, Yuko Okamatsu-Ogura, Takeshi Yoneshiro, Shingo Kajimura, Masayuki Saito, Wataru Ogawa
Summary: The study highlights the importance of KLF15 in regulating fuel switching between glucose and fatty acids in brown adipose tissue. This is achieved through its impact on fatty acid and glucose oxidation, as well as pyruvate dehydrogenase complex activity in BAT.
JOURNAL OF DIABETES INVESTIGATION
(2021)
Article
Pharmacology & Pharmacy
Huiling Hu, Nannan Sun, Haiyan Du, Yuqing He, Kunyi Pan, Xiuli Liu, Xiaoxia Lu, Jie Wei, Mianmian Liao, Chaohui Duan
Summary: Previous studies have shown that PLZF plays a role in promoting gluconeogenic gene expression, hepatic glucose output, and consequent hyperglycemia. However, its role in regulating lipid metabolism was unknown. This study revealed that PLZF is an essential regulator of hepatic lipid and glucose metabolism. Overexpression of PLZF in the liver led to fatty liver, inflammation, impaired glucose tolerance, and insulin sensitivity. Knockdown of PLZF in obese mice alleviated hepatic steatosis. The underlying mechanism involved PLZF activating SREBP-1c gene transcription by binding to its promoter fragment, which depended on its interaction with SIRT1 to induce a repressor-to-activator conversion. These findings suggest that modulating PLZF expression in the liver could be a potential therapeutic approach for treating NAFLD.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Priscila L. Zimath, Milena S. Almeida, Maciel A. Bruxel, Alex Rafacho
Summary: In this study, the potential therapeutic application of mometasone furoate (MF) with fewer adverse effects was investigated. It was found that MF maintained anti-inflammatory activity, but intraperitoneal administration led to glucose intolerance, while oral administration did not. Regardless of the route of administration, MF reduced insulin sensitivity and increased pancreatic beta-cell mass. Overall, oral administration of MF minimized the adverse effects on metabolism.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Endocrinology & Metabolism
Crystal S. Conn, Haojun Yang, Harrison J. Tom, Kenji Ikeda, Juan A. Oses-Prieto, Hieu Vu, Yasuo Oguri, Supna Nair, Ryan M. Gill, Shingo Kajimura, Ralph J. DeBerardinis, Alma L. Burlingame, Davide Ruggero
Summary: This study reveals the translational control of lipid processing as a driver of high-fat-diet-induced weight gain and provides a pharmacological target to treat obesity.
Article
Endocrinology & Metabolism
Evelin Major, Ferenc Gyory, Daniel Horvath, Ilka Keller, Istvan Tamas, Karen Uray, Peter Fulop, Beata Lontay
Summary: In hyperthyroidism, SMTNL1 plays a crucial role in regulating insulin sensitivity, inhibiting JNK activity and non-genomic effects of T3, and restoring normal glucose transport responsiveness. It also controls glucose phosphorylation and balances glycolysis and glycogen synthesis by downregulating hexokinase II. SeaHorse analysis revealed that SMTNL1 overexpression counteracts the shift to glycolysis induced by T3 overload, suggesting its potential as a therapeutic target in insulin resistance associated with hyperthyroidism.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Review
Physiology
Lei Zhao, Yuqi Li, Qiuying Ding, Yanping Li, Yaxi Chen, Xiong Z. Ruan
Summary: Intestinal CD36 plays a vital role in regulating intestinal lipid uptake and hormone secretion, but further studies are needed to confirm its complex interactions with dietary lipids.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Biology
Andrew Kuo, Antonio Checa, Colin Niaudet, Bongnam Jung, Zhongjie Fu, Craig E. Wheelock, Sasha A. Singh, Masanori Aikawa, Lois E. Smith, Richard L. Proia, Timothy Hla
Summary: This study reveals the crucial role of endothelial sphingolipid biosynthesis in regulating vascular development, maintaining circulatory and peripheral organ sphingolipid levels, and contributing to lipid raft formation and efficient signaling. The deletion of SPTLC1 in endothelial cells leads to impaired proliferation, differentiation, and delayed retinal vascular development. Furthermore, EC-derived sphingolipid metabolites are in constant flux between the vasculature, circulation, and non-CNS organs, and play a role in hepatocyte response to stress.
Article
Cell Biology
Xue-Ming Zhu, Lin Li, Jian-Dong Bao, Jiao-Yu Wang, Shuang Liang, Li-Li Zhao, Chang-Li Huang, Jiong-Yi Yan, Ying-Ying Cai, Xi-Yu Wu, Bo Dong, Xiao-Hong Liu, Daniel J. Klionsky, Fu-Cheng Lin
Summary: This study identified a new VASt domain-containing protein, MoVast2, and uncovered its regulatory mechanism in M. oryzae. MoVast2 interacted with MoVast1 and MoAtg8, and colocalized at the PAS, leading to inappropriate autophagy progress in the Delta Movast2 mutant. Additionally, MoVast2 maintained lipid homeostasis and autophagy balance by regulating TOR activity in M. oryzae.
Article
Substance Abuse
Hermes Reyes-Caballero, Bongsoo Park, Jeffrey Loube, Ian Sanchez, Vinesh Vinayachandran, Youngshim Choi, Juhyung Woo, Justin Edwards, Marielle C. Brinkman, Thomas Sussan, Wayne Mitzner, Shyam Biswal
Article
Medicine, Research & Experimental
Sanjay Rajagopalan, Bongsoo Park, Rengasamy Palanivel, Vinesh Vinayachandran, Jeffrey A. Deiuliis, Roopesh Singh Gangwar, Lopa Das, Jinhu Yin, Youngshim Choi, Sadeer Al-Kindi, Mukesh K. Jain, Kasper D. Hansen, Shyam Biswal
JOURNAL OF CLINICAL INVESTIGATION
(2020)
Article
Multidisciplinary Sciences
David R. Sweet, Neelakantan T. Vasudevan, Liyan Fan, Chloe E. Booth, Komal S. Keerthy, Xudong Liao, Vinesh Vinayachandran, Yoichi Takami, Derin Tugal, Nikunj Sharma, E. Ricky Chan, Lilei Zhang, Yulan Qing, Stanton L. Gerson, Chen Fu, Anthony Wynshaw-Boris, Panjamaporn Sangwung, Lalitha Nayak, Paul Holvoet, Keiichiro Matoba, Yuan Lu, Guangjin Zhou, Mukesh K. Jain
NATURE COMMUNICATIONS
(2020)
Article
Medicine, Research & Experimental
Xudong Liao, Eugene Chang, Xinmiao Tang, Ippei Watanabe, Rongli Zhang, Hyun-Woo Jeong, Ralf H. Adams, Mukesh K. Jain
Summary: This study identifies macrophages as a key regulator in the pathogenesis of TTS and suggests that inhibiting macrophage infiltration or activation could improve cardiac function in TTS patients.
Article
Biochemistry & Molecular Biology
Liyan Fan, David R. Sweet, Erica K. Fan, Domenick A. Prosdocimo, Annmarie Madera, Zhen Jiang, Roshan Padmanabhan, Saptarsi M. Haldar, Vinesh Vinayachandran, Mukesh K. Jain
Summary: Skeletal muscle dynamically regulates systemic nutrient homeostasis through transcriptional adaptations. KLF15, a zinc-finger transcription factor, plays a critical role in metabolic adaptation by binding to distal intergenic regions and regulating genes related to circadian rhythmicity and lipid metabolism. KLF15 and PPAR delta have interdependent interactions and co-regulate lipid metabolic gene programs.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Genetics & Heredity
Vinesh Vinayachandran, Purnima Bhargava
Summary: This study found that the small non-histone protein Nhp6 in budding yeast specifically influences the transcription of the SNR6 gene. The absence of Nhp6 or disruption of the T-7 sequence leads to downstream initiation of transcription. Additionally, the relative rotational orientation of the promoter elements in nucleosomal DNA and Nhp6 regulate the transcription of the SNR6 gene with precision.
FRONTIERS IN GENETICS
(2022)
Article
Cell Biology
Lalitha Nayak, David R. Sweet, Asha Thomas, Stephanie D. Lapping, Kenneth Kalikasingh, Annmarie Madera, Vinesh Vinayachandran, Roshan Padmanabhan, Neelakantan T. Vasudevan, Jay T. Myers, Alex Y. Huang, Alvin Schmaier, Nigel Mackman, Xudong Liao, Andrei Maiseyeu, Mukesh K. Jain
Summary: Arterial and venous thrombosis are major global diseases with common mechanisms involving neutrophils. This study identified neutrophils as key effectors in thrombosis and demonstrated the feasibility of targeting them using immunoregulatory nanoparticles. Moreover, key molecular events and regulators of neutrophil activation were identified, providing potential targets for therapeutics against immunothrombosis.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Multidisciplinary Sciences
Liyan Fan, Alexander F. Lesser, David R. Sweet, Komal S. Keerthy, Yuan Lu, Ernest R. Chan, Vinesh Vinayachandran, Olga Ilkayeva, Tapatee Das, Christopher B. Newgard, Mukesh K. Jain
Summary: Brown adipose tissue (BAT) is crucial for maintaining metabolic health and survival by regulating and utilizing nutrient resources. The transcription factor KLF15 plays a critical role in the metabolic flexibility of BAT.
Article
Cardiac & Cardiovascular Systems
David R. Sweet, Roshan Padmanabhan, Xudong Liao, Himanshu R. Dashora, Xinmiao Tang, Lalitha Nayak, Rajan Jain, Sarah De Val, Vinesh Vinayachandran, Mukesh K. Jain
Summary: This study investigates the transcriptional control mechanisms of KLF2 and KLF4 in heart and lung endothelium. The results show that KLF2 and KLF4 use open chromatin regions in promoters and enhancers, and bind context-specifically to govern transcription in microvasculature. This work provides insight into the transcriptional and functional heterogeneity seen in vascular populations, and establishes tools for exploring microvascular endothelial dynamics in vivo.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2023)
Article
Medicine, Research & Experimental
Xinmiao Tang, Peiwei Wang, Rongli Zhang, Ippei Watanabe, Eugene Chang, Vinesh Vinayachandran, Lalitha Nayak, Stephanie Lapping, Sarah Liao, Annmarie Madera, David R. Sweet, Jiemeng Luo, Jinsong Fei, Hyun-Woo Jeong, Ralf H. Adams, Teng Zhang, Xudong Liao, Mukesh K. Jain
Summary: The role of inflammation and inflammatory cells, particularly neutrophils, in cardiac hypertrophy and heart failure has been investigated in this study. It was found that neutrophils play a crucial role in the pathogenesis and progression of heart failure by triggering thrombosis in small myocardial vessels through the KLF2/NETosis pathway. Targeting neutrophils, NETosis, or thrombosis can alleviate pathological changes and preserve cardiac dysfunction.
JOURNAL OF CLINICAL INVESTIGATION
(2022)