FABP4 inhibitor BMS309403 decreases saturated-fatty-acid-induced endoplasmic reticulum stress-associated inflammation in skeletal muscle by reducing p38 MAPK activation

Bosquet, Alba; Girona, Josefa; Guaita‐Esteruelas, Sandra; Heras, Mercedes; Saavedra‐García, Paula; Martínez-Micaelo, Neus; Masana, Luís; Rodríguez-Calvo, Ricardo

doi:10.1016/j.bbalip.2018.03.004

Cited by 43 publications

(31 citation statements)

References 36 publications

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“…These secreted factors rapidly induce excessive FA oxidation in human myotubes, which leads to oxidative stress, p38 activation, and impaired muscle growth. Moreover, FA binding protein 4 (FABP4) inhibitor reduces FA-induced ER stress-associated inflammation in skeletal muscles by reducing p38 MAPK activation [ 202 ]. Additionally, angiotensin II induces insulin resistance in skeletal muscle by a mechanism dependent on oxidative stress and activation of p38, which results in decreased function of glucose transporter type 4 [ 203 ].…”

Section: The Conventional Mapksmentioning

confidence: 99%

Impact of Conventional and Atypical MAPKs on the Development of Metabolic Diseases

Kassouf

Sumara

2020

Biomolecules

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The family of mitogen-activated protein kinases (MAPKs) consists of fourteen members and has been implicated in regulation of virtually all cellular processes. MAPKs are divided into two groups, conventional and atypical MAPKs. Conventional MAPKs are further classified into four sub-families: extracellular signal-regulated kinases 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK1, 2 and 3), p38 (α, β, γ, δ), and extracellular signal-regulated kinase 5 (ERK5). Four kinases, extracellular signal-regulated kinase 3, 4, and 7 (ERK3, 4 and 7) as well as Nemo-like kinase (NLK) build a group of atypical MAPKs, which are activated by different upstream mechanisms than conventional MAPKs. Early studies identified JNK1/2 and ERK1/2 as well as p38α as a central mediators of inflammation-evoked insulin resistance. These kinases have been also implicated in the development of obesity and diabetes. Recently, other members of conventional MAPKs emerged as important mediators of liver, skeletal muscle, adipose tissue, and pancreatic β-cell metabolism. Moreover, latest studies indicate that atypical members of MAPK family play a central role in the regulation of adipose tissue function. In this review, we summarize early studies on conventional MAPKs as well as recent findings implicating previously ignored members of the MAPK family. Finally, we discuss the therapeutic potential of drugs targeting specific members of the MAPK family.

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Section: The Conventional Mapksmentioning

confidence: 99%

Impact of Conventional and Atypical MAPKs on the Development of Metabolic Diseases

Kassouf

Sumara

2020

Biomolecules

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“…Six-week-old C57BL/6J male mice were maintained on a standard light–dark cycle (12 h light–dark cycle) and temperature (21 ± 1 °C) conditions with ad libitum access to food and water. The animals were randomly distributed into two experimental groups ( n = 10 each) and fed one of two diets for 12 weeks: a standard chow diet (STD: 10% kcal from fat; Panlab; Barcelona, Spain) and a high-fat diet (HFD: 60% kcal from fat; Panlab; Barcelona, Spain) [ 31 , 32 ]. After this period, the mice were euthanized, and the livers were immediately frozen in liquid nitrogen and stored at −80 °C.…”

Section: Methodsmentioning

confidence: 99%

“…mRNA levels were assessed by real-time RT-PCR as previously described [ 31 ]. Total RNA was isolated from livers using TRI Reagent (Sigma-Aldrich; Barcelona, Spain) according to the manufacturer’s recommendations.…”

Section: Methodsmentioning

confidence: 99%

“…TaqMan gene expression assays-on-demand (IDT; Leuven, Belgium) were used for mouse peroxisome proliferator-activated receptor γ coactivator-1α ( Pgc1α ) (Mm.PT.58.17390716); mouse acyl-Coenzyme A (CoA) synthetase ( Acs ) (Mm.PT.58.29312796); mouse medium-chain acyl-CoA dehydrogenase ( Acadm ) (Mm.PT.58.9004416); mouse vey-long-chain acyl-CoA dehydrogenase ( Acadvl ) (Mm.PT.58.30103666); mouse acyl-CoA oxidase 1 ( Acox1 ) (Mm.PT.58.5874703); mouse fatty acid synthase ( Fas ) (Mm.PT.58.14276063); mouse glycerol-3-phosphate acyltransferase ( Gpat1 ) (Mm.PT.58.12176691); mouse diacylglycerol O-acyltransferase 2 ( Dgat2 ) (Mm.PT.58.28629966); mouse collagen, type I, alpha 1 ( Col1a1 ) (Mm.PT.58.7562513); mouse collagen, type I, alpha 2 ( Col1a2 ) (Mm.PT.58.5206680); mouse chemokine (C-C motif) ligand 2 ( Ccl2 ) (Mm.PT.58.42151692); and mouse tumor necrosis factor ( Tnf ) (Mm.PT.58.12575861). TATA-binding protein ( Tbp ) (Mm.PT.58.10867035) was used as the endogenous control [ 31 ].…”

Section: Methodsmentioning

confidence: 99%

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Hepatic Lipidomics and Molecular Imaging in a Murine Non-Alcoholic Fatty Liver Disease Model: Insights into Molecular Mechanisms

et al. 2020

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An imbalance between hepatic fatty acid uptake and removal results in ectopic fat accumulation, which leads to non-alcoholic fatty liver disease (NAFLD). The amount and type of accumulated triglycerides seem to play roles in NAFLD progression; however, a complete understanding of how triglycerides contribute to NAFLD evolution is lacking. Our aim was to evaluate triglyceride accumulation in NAFLD in a murine model and its associations with molecular mechanisms involved in liver damage and adipose tissue-liver cross talk by employing lipidomic and molecular imaging techniques. C57BL/6J mice fed a high-fat diet (HFD) for 12 weeks were used as a NAFLD model. Standard-diet (STD)-fed animals were used as controls. Standard liver pathology was assessed using conventional techniques. The liver lipidome was analyzed by liquid chromatography–mass spectrometry (LC–MS) and laser desorption/ionization–mass spectrometry (LDI–MS) tissue imaging. Liver triglycerides were identified by MS/MS. The transcriptome of genes involved in intracellular lipid metabolism and inflammation was assessed by RT-PCR. Plasma leptin, resistin, adiponectin, and FABP4 levels were determined using commercial kits. HFD-fed mice displayed increased liver lipid content. LC–MS analyses identified 14 triglyceride types that were upregulated in livers from HFD-fed animals. Among these 14 types, 10 were identified in liver cross sections by LDI–MS tissue imaging. The accumulation of these triglycerides was associated with the upregulation of lipogenesis and inflammatory genes and the downregulation of β-oxidation genes. Interestingly, the levels of plasma FABP4, but not of other adipokines, were positively associated with 8 of these triglycerides in HFD-fed mice but not in STD-fed mice. Our findings suggest a putative role of FABP4 in the liver-adipose tissue cross talk in NAFLD.

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“…Recently, a variety of effective FABP4 inhibitors have been developed [15], but unfortunately, none of them is currently in the clinical research phases, and only BMS309403 ( Figure 1) has been systematically studied in both in vitro and in vivo animal models [16][17][18]. In Table 1 are reported the different classes of FABP4 inhibitors [15], in Figure 1 and Table 2 some representative examples and their biological evaluations, respectively.…”

Section: Introductionmentioning

confidence: 99%

3D-QSAR assisted identification of FABP4 inhibitors: An effective scaffold hopping analysis/QSAR evaluation

Floresta

Cilibrizzi

Abbate

et al. 2019

Bioorganic Chemistry

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FABP4 inhibitor BMS309403 decreases saturated-fatty-acid-induced endoplasmic reticulum stress-associated inflammation in skeletal muscle by reducing p38 MAPK activation

Cited by 43 publications

References 36 publications

Impact of Conventional and Atypical MAPKs on the Development of Metabolic Diseases

Impact of Conventional and Atypical MAPKs on the Development of Metabolic Diseases

Hepatic Lipidomics and Molecular Imaging in a Murine Non-Alcoholic Fatty Liver Disease Model: Insights into Molecular Mechanisms

3D-QSAR assisted identification of FABP4 inhibitors: An effective scaffold hopping analysis/QSAR evaluation

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