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Ampk ko mice

Lingyan Wu, Lina Zhang, Bohan Li, Haowen Jiang, Yanan Duan, Zhifu Xie, Lin Shuai, Jia Li, Jingya Li
Obesity occurs when excess energy accumulates in white adipose tissue (WAT), whereas brown adipose tissue (BAT), which is specialized in dissipating energy through thermogenesis, potently counteracts obesity. White adipocytes can be converted to thermogenic "brown-like" cells (beige cells; WAT browning) under various stimuli, such as cold exposure. AMP-activated protein kinase (AMPK) is a crucial energy sensor that regulates energy metabolism in multiple tissues. However, the role of AMPK in adipose tissue function, especially in the WAT browning process, is not fully understood...
2018: Frontiers in Physiology
Diana Moreira, Jérôme Estaquier, Anabela Cordeiro-da-Silva, Ricardo Silvestre
The study of host AMP-activated protein kinase (AMPK) activation during Leishmania infection imposes distinct types of techniques to measure protein expression and activation, as well as to quantify, at transcription and translational levels, its downstream targets. The investigation of host AMPK protein modulation during Leishmania infection should primarily be assessed during in vitro infections using as a host murine bone marrow-derived macrophages (BMMos). The infection outcome is assessed measuring the percentage of infected cells in the context of BMMos...
2018: Methods in Molecular Biology
Tarek A M Almabrouk, Anna D White, Azizah B Ugusman, Dominik S Skiba, Omar J Katwan, Husam Alganga, Tomasz J Guzik, Rhian M Touyz, Ian P Salt, Simon Kennedy
Background and aim: Perivascular adipose tissue (PVAT) positively regulates vascular function through production of factors such as adiponectin but this effect is attenuated in obesity. The enzyme AMP-activated protein kinase (AMPK) is present in PVAT and is implicated in mediating the vascular effects of adiponectin. In this study, we investigated the effect of an obesogenic high fat diet (HFD) on aortic PVAT and whether any changes involved AMPK. Methods: Wild type Sv129 (WT) and AMPKα1 knockout (KO) mice aged 8 weeks were fed normal diet (ND) or HFD (42% kcal fat) for 12 weeks...
2018: Frontiers in Physiology
Zai-Ming Liu, Qian-Xue Chen, Zhi-Biao Chen, Dao-Feng Tian, Ming-Chang Li, Jun-Min Wang, Long Wang, Bao-Hui Liu, Shen-Qi Zhang, Fei Li, Hui Ye, Long Zhou
Traumatic brain injury (TBI) is a leading cause of disability and mortality in young adults worldwide. The pathophysiology is not fully understood. Programmed necrosis (necroptosis) is a newly identified mechanism of cell death combining features of both apoptosis and necrosis. Receptor-interacting protein 3 (RIP3) plays an important role in programmed necrosis. However, the effect of RIP3-related pathway in TBI is little to be known. We attempted to explore the significance of RIP3 in regulating TBI in vivo...
February 19, 2018: Biochemical and Biophysical Research Communications
Yanbo Fan, Haocheng Lu, Wenying Liang, Minerva T Garcia-Barrio, Yanhong Guo, Ji Zhang, Tianqing Zhu, Yibai Hao, Jifeng Zhang, Y E Chen
<u>Rationale:</u> Post-ischemic angiogenesis is critical to limit the ischemic tissue damage and improve the blood flow recovery. The regulation and the underlying molecular mechanisms of post-ischemic angiogenesis are not fully unraveled. Transcription factor-EB (TFEB) is emerging as a master gene for autophagy and lysosome biogenesis. However, the role of TFEB in vascular disease is less understood. <u>Objective:</u> We aimed to determine the role of endothelial TFEB in post-ischemic angiogenesis and its underlying molecular mechanism...
February 21, 2018: Circulation Research
Chen Li, Wanqing Sun, Chunhu Gu, Zheng Yang, Nanhu Quan, Jingrun Yang, Zhaoling Shi, Lu Yu, Heng Ma
Clinical observations have demonstrated a link between chronic pain and increased ischemic heart disease mortality, but the mechanisms remain elusive. Reactive aldehydes have recently been confirmed as a new player in pain pathologies, while our previous study demonstrated that reactive aldehydes (4-HNE) induced carbonyl stress contributing to myocardial ischemic intolerance. The aim of this study was to explore whether chronic pain increases susceptibility to myocardial ischemia/reperfusion (MI/R) injury and to investigate the underlying mechanisms focusing on toxic aldehyde and carbonyl stress...
2018: Theranostics
Charlotte C Bavley, Richard C Rice, Delaney K Fischer, Amanda K Fakira, Maureen Byrne, Maria Kosovsky, Bryant K Rizzo, Dolores Del Prete, Armin Alaedini, Jose A Morón, Joseph J Higgins, Luciano D'Adamio, Anjali M Rajadhyaksha
A homozygous nonsense mutation in the cereblon ( CRBN ) gene results in autosomal recessive, non-syndromic intellectual disability (ARNSID) that is devoid of other phenotypic features, suggesting a critical role of CRBN in mediating learning and memory. In this study, we demonstrate that adult male Crbn knockout ( Crbn KO ) mice exhibit deficits in hippocampal-dependent learning and memory tasks that are recapitulated by focal knockout of Crbn in the adult dorsal hippocampus, with no changes in social or repetitive behavior...
February 19, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Ning Xu, Hao Meng, Tian-Yi Liu, Ying-Li Feng, Yuan Qi, Dong-Huan Zhang, Hong-Lei Wang
Insulin resistance induced by a high-fat diet (HFD) is related to metabolic diseases, and sterol O-acyltransferase 1 (SOAT1) is a key enzyme for the biosynthesis of cholesteryl ester. In the present study, wild-type (WT) mice and SOAT1-knockout (KO) mice with a C57BL6 background fed a HFD were used to explore the role of SOAT1 in the hypothalamus. The results show that the WT mice exhibited a significant increase in body weight as well as hepatic histologic changes; they also had a lower glucose and insulin tolerance than the WT mice fed a normal diet...
February 14, 2018: Biochemical and Biophysical Research Communications
Haoming Zhou, Han Wang, Ming Ni, Shi Yue, Yongxiang Xia, Ronald W Busuttil, Jerzy W Kupiec-Weglinski, Ling Lu, Xuehao Wang, Yuan Zhai
BACKGROUND & AIMS: Glycogen synthase kinase 3β (Gsk3β) is a ubiquitously expressed kinase with distinctive functions in different types of cells. Although its roles in regulating innate immune activation and ischemia and reperfusion injuries (IRI) have been well documented, underlying mechanisms remain ambiguous, due in part to the lack of cell-specific tools in vivo. METHODS: We created a myeloid-specific Gsk3β KO strain to study its function in macrophages in a murine liver partial warm ischemia model...
February 13, 2018: Journal of Hepatology
Yan You, Wan-Zhen Li, Sulin Zhang, Bin Hu, Yue-Xuan Li, Hai-Dong Li, Huan-Huan Tang, Qian-Wen Li, Yun-Yun Guan, Li-Xin Liu, Wei-Lian Bao, Xiaoyan Shen
BACKGROUND & AIMS: Alcoholic liver disease is a major cause of morbidity and mortality worldwide. However, the cellular defense mechanisms underlying ALD are not well understood. Recent studies highlight the involvement of chaperone-mediated autophagy (CMA) in regulating hepatic lipid metabolism. Sorting nexin (SNX) 10 has a regulatory function in endo-lysosomal trafficking and stabilization. Here we investigated the roles of SNX10 in CMA activation and the pathogenesis of alcohol-induced liver injury and steatosis...
February 13, 2018: Journal of Hepatology
Hong Yang, Anyun Feng, Sundong Lin, Lechu Yu, Xiufei Lin, Xiaoqing Yan, Xuemian Lu, Chi Zhang
Our previous studies showed that both exogenous and endogenous FGF21 inhibited cardiac apoptosis at the early stage of type 1 diabetes. Whether FGF21 induces preventive effect on type 2 diabetes-induced cardiomyopathy was investigated in the present study. High-fat-diet/streptozotocin-induced type 2 diabetes was established in both wild-type (WT) and FGF21-knockout (FGF21-KO) mice followed by treating with FGF21 for 4 months. Diabetic cardiomyopathy (DCM) was diagnosed by significant cardiac dysfunction, remodeling, and cardiac lipid accumulation associated with increased apoptosis, inflammation, and oxidative stress, which was aggravated in FGF21-KO mice...
February 14, 2018: Cell Death & Disease
Lin Wang, Nanhu Quan, Wanqing Sun, Xu Chen, Courtney Cates, Thomas Rousselle, Xinchun Zhou, Xuezhong Zhao, Ji Li
Aim: A longevity gene, Sirtuin 1 (SIRT1) and energy sensor AMP-activated protein kinase (AMPK) have common activators such as caloric restriction, oxidative stress and exercise. The objective of this study is to characterize the role of cardiomyocyte SIRT1 in age-related impaired ischemic AMPK activation and increased susceptibility to ischemic insults. Methods and Results: Mice were subjected to ligation of left anterior descending coronary artery for in vivo ischemic models...
February 2, 2018: Cardiovascular Research
Yuuki Shimizu, Rohini Polavarapu, Kattri-Liis Eskla, Chad K Nicholson, Christopher A Koczor, Rui Wang, William Lewis, Sruti Shiva, David J Lefer, John W Calvert
BACKGROUND: Hydrogen sulfide (H2 S) is an important regulator of mitochondrial bioenergetics, but its role in regulating mitochondrial biogenesis is not well understood. Using both genetic and pharmacological approaches, we sought to determine if H2 S levels directly influenced cardiac mitochondrial content. RESULTS: Mice deficient in the H2 S-producing enzyme, cystathionine γ-lyase (CSE KO) displayed diminished cardiac mitochondrial content when compared to wild-type hearts...
January 29, 2018: Journal of Molecular and Cellular Cardiology
Dennis K Fix, Justin P Hardee, Song Gao, Brandon N VanderVeen, Kandy T Velazquez, James A Carson
The IL-6 cytokine family activates intracellular signaling pathways through glycoprotein 130 (gp130), and this signaling has established regulatory roles in muscle glucose metabolism and proteostasis. Although the IL-6 family has been implicated as myokines regulating the muscle's metabolic response to exercise, gp130's role in mitochondrial quality control involving fission, fusion, mitophagy and biogenesis is not well understood. Therefore, we examined gp130's role in basal and exercise-trained muscle mitochondrial quality control...
February 1, 2018: Journal of Applied Physiology
Cong Yao, Xiong Guo, Wan-Xia Yao, Chun Zhang
Diabetes mellitus is a major cause to induce osteoporosis. Though the pathogenesis of osteoporosis progression has been well investigated, its still not fully understood. Recently, cereblon (CRBN) was considered as a negative modulator of adenosine monophosphate-activated protein kinase (AMPK) in vitro and in vivo. Here, we presented results indicating that CRBN could effectively regulate osteoporosis development. In STZ-induced wild type (WT) mice with diabetes, the osteoclasts were highly increased along with the deterioration of bone structure...
January 15, 2018: Biochemical and Biophysical Research Communications
Nadia Boudaba, Allison Marion, Camille Huet, Rémi Pierre, Benoit Viollet, Marc Foretz
Nonalcoholic fatty liver disease is a highly prevalent component of disorders associated with disrupted energy homeostasis. Although dysregulation of the energy sensor AMP-activated protein kinase (AMPK) is viewed as a pathogenic factor in the development of fatty liver its role has not been directly demonstrated. Unexpectedly, we show here that liver-specific AMPK KO mice display normal hepatic lipid homeostasis and are not prone to fatty liver development, indicating that the decreases in AMPK activity associated with hepatic steatosis may be a consequence, rather than a cause, of changes in hepatic metabolism...
January 9, 2018: EBioMedicine
Nanhu Quan, Lin Wang, Xu Chen, Chelsea Luckett, Courtney Cates, Thomas Rousselle, Yang Zheng, Ji Li
We have revealed that a novel stress-inducible protein, Sestrin2, declines in the heart with aging. Moreover, there is an interaction between Sestrin2 and energy sensor AMPK in the heart in response to ischemic stress. The objective of this study is to determine whether Sestrin2-AMPK complex modulates PGC-1α in the heart and protects the heart from ischemic insults. In order to characterize the role of cardiac Sestrin2-AMPK signaling cascade in aging, C57BL/6 wild type young mice (3-4months), aged mice (24-26months) and young Sestrin2 KO mice were subjected to left anterior descending coronary artery occlusion for in vivo regional ischemia...
January 8, 2018: Journal of Molecular and Cellular Cardiology
Mehmet E Yalvac, Jakkrit Amornvit, Cilwyn Braganza, Lei Chen, Syed-Rehan A Hussain, Kimberly M Shontz, Chrystal L Montgomery, Kevin M Flanigan, Sarah Lewis, Zarife Sahenk
BACKGROUND: Previous studies in patients with limb-girdle muscular dystrophy type 2A (LGMD2A) have suggested that calpain-3 (CAPN3) mutations result in aberrant regeneration in muscle. METHODS: To gain insight into pathogenesis of aberrant muscle regeneration in LGMD2A, we used a paradigm of cardiotoxin (CTX)-induced cycles of muscle necrosis and regeneration in the CAPN3-KO mice to simulate the early features of the dystrophic process in LGMD2A. The temporal evolution of the regeneration process was followed by assessing the oxidative state, size, and the number of metabolic fiber types at 4 and 12 weeks after last CTX injection...
December 14, 2017: Skeletal Muscle
Badr Alzahrani, Tristan Iseli, Mehdi Ramezani-Moghadam, Vikki Ho, Miriam Wankell, Eun Jin Sun, Liang Qiao, Jacob George, Lionel W Hebbard
Activation of the adiponectin (APN) signaling axis retards liver fibrosis. However, understanding of the role of AdipoR1 and AdipoR2 in mediating this response is still rudimentary. Here, we sought to elucidate the APN receptor responsible for limiting liver fibrosis by employing AdipoR1 and AdipoR2 knock-out mice in the carbon tetrachloride (CCl4) model of liver fibrosis. In addition, we knocked down receptor function in primary hepatic stellate cells (HSCs) in vitro. Following the development of fibrosis, AdipoR1 and AdipoR2 KO mice had no quantitative difference in fibrosis by Sirius red staining...
December 10, 2017: Biochimica et Biophysica Acta
Minchan Gil, Yun Kyu Kim, Ha Yeong Kim, Hyo-Kyung Pak, Chan-Sik Park, Kyung Jin Lee
Cereblon (CRBN) has a pleiotropic role in important cellular processes and is a potential therapeutic target in several diseases, including mental retardation, cancer, and metabolic disorders. The role of CRBN in polymicrobial sepsis induced by cecal ligation and puncture (CLP) was investigated using CRBN-deficient (KO) mice. Survival following CLP was significantly higher in KO mice compared to wild-type (WT) controls (50% vs 0% at day 6 after CLP). The improved survival of KO mice was accompanied by reduced peripheral blood bacterial load and lung injury...
January 1, 2018: Biochemical and Biophysical Research Communications
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