Flurbiprofen Ameliorates Glucose Deprivation-Induced Leptin Resistance

Hosoi, Toru; Suyama, Yuka; Kayano, Takaaki; Ozawa, Koichiro

doi:10.3389/fphar.2016.00354

Cited by 6 publications

(4 citation statements)

References 30 publications

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“…RT-PCR analysis. RT-PCR analysis was performed as described previously (26). Briefly, total RNA was isolated using the TriPure Isolation Reagent (Roche Molecular Biochemicals) according to the manufacturer's instruction.…”

Section: Methodsmentioning

confidence: 99%

Possible involvement of 4-hydroxy-2-nonenal in the pathogenesis of leptin resistance in obesity

Hosoi

Kuwamura

Thon

et al. 2019

American Journal of Physiology-Cell Physiology

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Insensitivity to the antiobesity hormone, leptin, has been suggested to be involved in the pathogenesis of obesity. However, the pathological mechanisms underlying the development of leptin resistance are not well-understood. This study aimed to examine the pathological mechanisms of leptin resistance in obesity. In the present study, we found that 4-hydroxy-2-nonenal (4-HNE), an aldehyde, may be involved in the development of leptin resistance. The SH-SY5Y-Ob-Rb human neuroblastoma cell line, transfected to express the Ob-Rb leptin receptor stably, was treated with 4-HNE, and leptin-induced signal transduction was analyzed. We found that 4-HNE dose- and time-dependently inhibited leptin-induced signal transducer and activator of transcription 3 (STAT3) phosphorylation, a major antiobesity signal of leptin. On the other hand, 4-HNE did not affect tyrosine phosphorylation of broad cellular proteins, suggesting that the inhibitory effect may be selective to leptin signaling. Mechanistically, 4-HNE induced the eukaryotic initiation factor 2α-CCAAT/enhancer-binding protein homologous protein arm of endoplasmic reticulum stress signaling, which may be involved in the pathogenesis of leptin resistance. Overall, these results suggest that 4-HNE may partly affect endoplasmic reticulum stress-induced unfolded protein response signaling and may be involved in the pathogenesis of leptin resistance.

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Section: Methodsmentioning

confidence: 99%

Possible involvement of 4-hydroxy-2-nonenal in the pathogenesis of leptin resistance in obesity

Hosoi

Kuwamura

Thon

et al. 2019

American Journal of Physiology-Cell Physiology

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“…Total RNA was isolated and RT-PCR was performed as previously described, albeit with a few modifications ( Hosoi et al, 2016 ). For PCR amplification, we used the Expand High Fidelity kit (Roche AG) and KAPA Taq Extra PCR kit (KAPA Biosystems).…”

Section: Methodsmentioning

confidence: 99%

Incorporation of the Endoplasmic Reticulum Stress-Induced Spliced Form of XBP1 mRNA in the Exosomes

2018

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It is known that endoplasmic reticulum (ER) and nucleus communicate with each other to cope with ER stress. However, the mechanisms through which extracellular transmission of ER stress occurs remain unexplored. When the ER stress-induced unfolded protein response (UPR) is activated, the X-box binding protein 1 (XBP1) mRNA is spliced by inositol-requiring enzyme-1α (IRE1α) to produce the spliced form of XBP1 (sXBP1). In the present study, we found that sXBP1 mRNA in the cell may be incorporated into the exosomes and was released extracellularly. We found that the ratio of the mRNA levels of sXBP1 to unspliced XBP1 (uXBP1) in the exosome was higher than that of cells in MIN6 mouse pancreatic β cells. A similar effect was observed when XBP1 splicing was induced by overexpressing IRE1α in HEK293T cells. These results suggest that the incorporation of sXBP1 into the exosomes is a novel mechanism of UPR transmitted to extracellularly, which would be triggered when cells are exposed to stress.

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“…It belongs to the class of drugs for the treatment of obesity due to its ability to reduce the accumulation of unfolded proteins, which causes endoplasmic reticulum stress, which is responsible for obesity development. Its anti-obesity properties are due to its capacity to attenuate leptin resistance and the subsequent amelioration of glucose deprivation-induced leptin resistance, which is involved in the pathophysiology of obesity [ 19 ]. NSAIDs, however, have a lot of adverse effects: enhanced gut permeability and inflammation, anemia, malabsorption, and mucosal ulceration.…”

Section: Introductionmentioning

confidence: 99%

Anti-Obesity and Anti-Inflammatory Effects of Novel Carvacrol Derivatives on 3T3-L1 and WJ-MSCs Cells

et al. 2023

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(1) Background: Obesity, a complex metabolic disease resulting from an imbalance between food consumption and energy expenditure, leads to an increase in adipocytes and chronic inflammatory conditions. The aim of this paper was to synthesize a small series of carvacrol derivatives (CD1-3) that are able to reduce both adipogenesis and the inflammatory status often associated with the progression of the obesity disease. (2) Methods: The synthesis of CD1-3 was performed using classical procedures in a solution phase. Biological studies were performed on three cell lines: 3T3-L1, WJ-MSCs, and THP-1. The anti-adipogenic properties of CD1-3 were evaluated using western blotting and densitometric analysis by assessing the expression of obesity-related proteins, such as ChREBP. The anti-inflammatory effect was estimated by measuring the reduction in TNF-α expression in CD1-3-treated THP-1 cells. (3) Results: CD1-3—obtained through a direct linkage between the carboxylic moiety of anti-inflammatory drugs (Ibuprofen, Flurbiprofen, and Naproxen) and the hydroxyl group of carvacrol—have an inhibitory effect on the accumulation of lipids in both 3T3-L1 and WJ-MSCs cell cultures and an anti-inflammatory effect by reducing TNF- α levels in THP-1 cells. (4) Conclusions: Considering the physicochemical properties, stability, and biological data, the CD3 derivative—obtained by a direct linkage between carvacrol and naproxen—resulted in the best candidate, displaying anti-obesity and anti-inflammatory effects in vitro.

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Flurbiprofen Ameliorates Glucose Deprivation-Induced Leptin Resistance

Cited by 6 publications

References 30 publications

Possible involvement of 4-hydroxy-2-nonenal in the pathogenesis of leptin resistance in obesity

Possible involvement of 4-hydroxy-2-nonenal in the pathogenesis of leptin resistance in obesity

Incorporation of the Endoplasmic Reticulum Stress-Induced Spliced Form of XBP1 mRNA in the Exosomes

Anti-Obesity and Anti-Inflammatory Effects of Novel Carvacrol Derivatives on 3T3-L1 and WJ-MSCs Cells

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