Adipose tissue and insulin resistance in obese

Biomedicine & Pharmacotherapy, Journal Year: 2021, Volume and Issue: 137, P. 111315 - 111315

Published: Feb. 7, 2021

Currently, obesity has become a global health issue and is referred to as an epidemic. Dysfunctional obese adipose tissue plays pivotal role in the development of insulin resistance. However, mechanism how dysfunctional obese-adipose develops insulin-resistant circumstances remains poorly understood. Therefore, this review attempts highlight potential mechanisms behind obesity-associated Multiple risk factors are directly or indirectly associated with increased obesity; among them, environmental factors, genetics, aging, gut microbiota, diets prominent. Once individual becomes obese, adipocytes increase their size; therefore, tissues larger dysfunctional, recruit macrophages, then these polarize pro-inflammatory states. Enlarged release excess free fatty acids (FFAs), reactive oxygen species (ROS), cytokines. Excess systemic FFAs dietary lipids enter inside cells non-adipose organs such liver, muscle, pancreas, deposited ectopic fat, generating lipotoxicity. Toxic dysregulate cellular organelles, e.g., mitochondria, endoplasmic reticulum, lysosomes. Dysregulated organelles ROS pro-inflammation, resulting inflammation. Long term low-grade inflammation prevents from its action signaling pathway, disrupts glucose homeostasis, results dysregulation. Overall, long-term overnutrition develop into resistance chronic through lipotoxicity, creating clinical conditions. This also shows that liver most sensitive organ undergoing impairment faster than other organs, thus, hepatic primary event leads subsequent peripheral

Language: Английский

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PI3K/AKT/mTOR signaling in gastric cancer: Epigenetics and beyond

Life Sciences, Journal Year: 2020, Volume and Issue: 262, P. 118513 - 118513

Published: Oct. 1, 2020

Language: Английский

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mTOR substrate phosphorylation in growth control

Cell, Journal Year: 2022, Volume and Issue: 185(11), P. 1814 - 1836

Published: May 1, 2022

Language: Английский

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The interplay of ROS and the PI3K/Akt pathway in autophagy regulation

Biotechnology and Applied Biochemistry, Journal Year: 2021, Volume and Issue: 69(1), P. 248 - 264

Published: Jan. 15, 2021

Autophagy causes the breakdown of damaged proteins and organelles to their constituent components. The phosphatidylinositol 3-kinase (PI3K) pathway played an important role in regulating autophagic response cells changing reactive oxygen species (ROS) levels. PI3K α catalytic subunit inhibits autophagy, while its β promotes autophagy changes ROS downstream Akt protein acts against initiation increases levels under nutrient-rich conditions. by activating a mechanistic target rapamycin complex 1 (mTORC1) arresting gene expression. AMP-activated kinase (AMPK) counteracts actions. mTORC1 mTORC2 inhibit moderate levels, but high can promote cellular senescence via autophagy. Phosphatase tensin homolog (PTEN) are negative regulators pathway, it has proautophagic activities. Studies conducted on treated with flavonoids ionizing radiation showed that increase flavonoid-treated groups corresponded higher PTEN lowered leading occurrence In contrast, evoked caused lowering incidence

Language: Английский

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Mechanism of interaction between autophagy and apoptosis in cancer

APOPTOSIS, Journal Year: 2021, Volume and Issue: 26(9-10), P. 512 - 533

Published: Sept. 12, 2021

Language: Английский

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Targeting the biology of aging with mTOR inhibitors

Nature Aging, Journal Year: 2023, Volume and Issue: 3(6), P. 642 - 660

Published: May 4, 2023

Language: Английский

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Autophagy in the diabetic heart: A potential pharmacotherapeutic target in diabetic cardiomyopathy

Ageing Research Reviews, Journal Year: 2021, Volume and Issue: 68, P. 101338 - 101338

Published: April 7, 2021

Language: Английский

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Targeting the Integrated Stress Response in Cancer Therapy

Frontiers in Pharmacology, Journal Year: 2021, Volume and Issue: 12

Published: Sept. 24, 2021

The integrated stress response (ISR) is an evolutionarily conserved intra-cellular signaling network which activated in to intrinsic and extrinsic stresses. Various stresses are sensed by four specialized kinases, PKR-like ER kinase (PERK), general control non-derepressible 2 (GCN2), double-stranded RNA-dependent protein (PKR) heme-regulated eIF2α (HRI) that converge on phosphorylation of serine 51 eIF2α. causes a global reduction synthesis triggers the translation specific mRNAs, including activating transcription factor 4 (ATF4). Although ISR promotes cell survival homeostasis, when severe or prolonged will shift regulate cellular apoptosis. We review pathway, regulation importance cancer therapy.

Language: Английский

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Challenges of fluoride pollution in environment: Mechanisms and pathological significance of toxicity – A review

Environmental Pollution, Journal Year: 2022, Volume and Issue: 304, P. 119241 - 119241

Published: April 1, 2022

Language: Английский

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Targeting the PI3K/AKT/mTOR and RAF/MEK/ERK pathways for cancer therapy

Molecular Biomedicine, Journal Year: 2022, Volume and Issue: 3(1)

Published: Dec. 21, 2022

The PI3K/AKT/mTOR and RAF/MEK/ERK pathways are commonly activated by mutations chromosomal translocation in vital targets. signaling pathway is dysregulated nearly all kinds of neoplasms, with the component this alternations. cascades used to conduct from cell surface nucleus mediate gene expression, cycle processes apoptosis. RAS, B-Raf, PI3K, PTEN frequent upstream alternative sites. These resulted growth downregulated two interact each other participate tumorigenesis. alterations suppress activity via AKT phosphorylation RAS inhibition. Several inhibitors targeting major components these have been supported FDA. Dozens agents attracted great attention assessed clinical trials. combination small molecular traditional regimens has also explored. Furthermore, dual provide new insight into antitumor activity. This review will further comprehensively describe genetic normal patients tumor discuss role targeted malignant neoplasm therapy. We hope promote a comprehensive understanding facilitating tumors help direct drug selection for

Language: Английский

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