Oxidative stress and inflammation: the root causes of aging DOI Creative Commons
Prasert Sobhon,

Savedvanich Gavin,

Sawaek Weerakiet

et al.

Exploration of Medicine, Journal Year: 2023, Volume and Issue: unknown, P. 127 - 156

Published: April 17, 2023

Oxygen free radicals [reactive oxygen species (ROS)] and nitrogen (RNS)] are generated by mitochondria during adenosine triphosphate synthesis, catalytic activities of cytochrome P450, nicotinamide adenine dinucleotide phosphate oxidases (NOXs), cyclooxygenases, nitric oxide synthases drug catabolism, phagocytosis, acute inflammation. Under normal circumstances, low levels ROS RNS provide redox signalings that control many essential physiological processes. As age progresses increase excessively due to dysfunctional mitochondria, dysregulated NOX, other free-radical generating sources, leading oxidative stress, which causes oxidation denaturation key cellular components including DNA, proteins, lipids, become abnormal, constituting damage-associated molecular pattern (DAMP), recognized as ‘non-self’ immune cells, inflammation is mediated nuclear factor kappa B-inflammasome, p38-c-Jun N-terminal kinase Janus kinase-signal transducer activator transcription pathways. DAMPs continuously released from damaged senescent causing an otherwise normally transient turning into systemic chronic inflammation, the root cause aging age-associated diseases (AADs). Cells restore balance activating erythroid 2-related 2 (Nrf2) pathway induces synthesis release antioxidation molecules enzymes haem oxygenase-1, also inhibits three inflammatory Furthermore, upregulation autophagy (AP) can get rid abnormal molecules, prevent generation DAMPs, attenuate Both AP Nrf2 decrease with age. The upregulations Nrf2, AP, downregulation controlled sensors energy stress levels, i.e., monophosphate-activated protein kinase, silent information regulator 1, Sestrins, well extracellular matrix, while mammalian targets for rapamycin complex a nutrient sensor, act in opposite direction. If these sensor systems becomes dysregulated, process accelerates, risk AADs increases.

Language: Английский

Role of irisin in physiology and pathology DOI Creative Commons
Shiqiang Liu, Fengqi Cui,

Kaiting Ning

et al.

Frontiers in Endocrinology, Journal Year: 2022, Volume and Issue: 13

Published: Sept. 26, 2022

Irisin, out-membrane part of fibronectin type III domain–containing 5 protein (FNDC5), was activated by Peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1α (PGC-1α) during physical exercise in skeletal muscle tissues. Most studies have reported that the concentration irisin is highly associated with health status. For instance, level significantly lower patients obesity, osteoporosis/fractures, atrophy, Alzheimer’s disease, and cardiovascular diseases (CVDs) but higher cancer. Irisin can bind to its integrin αV/β5 induce browning white fat, maintain glucose stability, keep bone homeostasis, alleviate cardiac injury. However, it unclear whether works directly binding receptors regulate regeneration, promote neurogenesis, liver inhibit cancer development. Supplementation recombinant or exercise-activated might be a successful strategy fight osteoporosis, injury, CVDs one go. Here, we summarize publications FNDC5/irisin from PubMed/Medline, Scopus, Web Science until March 2022, review role physiology pathology.

Language: Английский

Citations

81
Irisin reduces inflammatory signaling pathways in inflammation-mediated metabolic syndrome DOI Creative Commons

John J. Slate-Romano,

Naohiro Yano,

Ting C. Zhao

et al.

Molecular and Cellular Endocrinology, Journal Year: 2022, Volume and Issue: 552, P. 111676 - 111676

Published: May 13, 2022

Language: Английский

Citations

45
TNFα-induced NLRP3 inflammasome mediates adipocyte dysfunction and activates macrophages through adipocyte-derived lipocalin 2 DOI
Hafiz Muhammad Ahmad Javaid, Eun Jung Ko,

Esther Jin Joo

et al.

Metabolism, Journal Year: 2023, Volume and Issue: 142, P. 155527 - 155527

Published: March 3, 2023

Language: Английский

Citations

25
Altered Mitochondrial Function in MASLD: Key Features and Promising Therapeutic Approaches DOI Creative Commons
Tatjana Radosavljević,

Milica Branković,

Janko Samardžić

et al.

Antioxidants, Journal Year: 2024, Volume and Issue: 13(8), P. 906 - 906

Published: July 26, 2024

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty (NAFLD), encompasses a range of conditions from steatosis to steatohepatitis (NASH). Its prevalence, especially among patients with metabolic syndrome, highlights its growing global impact. The pathogenesis MASLD involves dysregulation, inflammation, oxidative stress, genetic factors and, notably, mitochondrial dysfunction. Recent studies underscore the critical role dysfunction in MASLD's progression. Therapeutically, enhancing function has gained interest, along lifestyle changes and pharmacological interventions targeting processes. FDA's approval resmetirom for metabolic-associated (MASH) fibrosis marks significant step. While represents progress, further research is essential understand MASLD-related fully. Innovative strategies like gene editing small-molecule modulators, alongside interventions, can potentially improve treatment. Drug repurposing new targets will advance therapy, addressing increasing burden. Therefore, this review aims provide better understanding identify more effective preventive treatment strategies.

Language: Английский

Citations

12
Resistance exercise upregulates Irisin expression and suppresses myocardial fibrosis following myocardial infarction via activating AMPK‐Sirt1 and inactivating TGFβ1‐Smad2/3 DOI
Hangzhuo Li, Shuguang Qin, Jie Tang

et al.

Acta Physiologica, Journal Year: 2024, Volume and Issue: 240(7)

Published: May 16, 2024

To reveal the contribution of Irisin in beneficial effects resistance exercise on myocardial fibrosis (MF) and cardiac function mice with infarction (MI).

Language: Английский

Citations

11
NAFLD Fibrosis Progression and Type 2 Diabetes: The Hepatic–Metabolic Interplay DOI Creative Commons
Simona Cernea

Life, Journal Year: 2024, Volume and Issue: 14(2), P. 272 - 272

Published: Feb. 18, 2024

The bidirectional relationship between type 2 diabetes and (non-alcoholic fatty liver disease) NAFLD is indicated by the higher prevalence worse disease course of one condition in presence other, but also apparent beneficial effects observed one, when other improved. This partly explained their belonging to a multisystemic that includes components metabolic syndrome shared pathogenetic mechanisms. Throughout progression more advanced stages, complex systemic local derangements are involved. During fibrogenesis, significant reprogramming occurs hepatic stellate cells, hepatocytes, immune engaging carbohydrate lipid pathways support high-energy-requiring processes. natural history evolves variable dynamic manner, probably due interaction number modifiable (diet, physical exercise, microbiota composition, etc.) non-modifiable (genetics, age, ethnicity, risk factors may intervene concomitantly, or subsequently/intermittently time. influence (and rate) fibrosis progression/regression. recognition control determine rapid (or its regression) critical, as stages associated with liver-related all-cause mortality.

Language: Английский

Citations

8
Inter-organ metabolic interaction networks in non-alcoholic fatty liver disease DOI Creative Commons
Yuhong Fan, Siyao Zhang, Ye Wang

et al.

Frontiers in Endocrinology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 9, 2025

Non-alcoholic fatty liver disease (NAFLD) is a multisystem metabolic disorder, marked by abnormal lipid accumulation and intricate inter-organ interactions, which contribute to systemic imbalances. NAFLD may progress through several stages, including simple steatosis (NAFL), non-alcoholic steatohepatitis (NASH), cirrhosis, potentially cancer. This closely associated with disorders driven overnutrition, key pathological processes dysregulation, impaired autophagy, mitochondrial dysfunction, endoplasmic reticulum (ER) stress, local inflammation. While hepatic metabolism in well-documented, further research into communication mechanisms crucial for deeper understanding of progression. review delves intrahepatic networks tissue-specific signaling mediators involved pathogenesis, emphasizing their impact on distal organs.

Language: Английский

Citations

1
Irisin alleviates hepatic steatosis by activating the autophagic SIRT3 pathway DOI Creative Commons
Ying Zhao, Jia Li,

Anran Ma

et al.

Chinese Medical Journal, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 18, 2025

Abstract Background: Disruption of hepatic lipid homeostasis leads to excessive triglyceride accumulation and the development metabolic dysfunction-associated steatotic liver disease (MASLD). Autophagy, a critical process in metabolism, is impaired MASLD pathogenesis. Irisin, skeletal muscle-driven myokine, regulates but its impact on metabolism not well understood. Here, we aimed explore role irisin steatosis underlying mechanisms involved. Methods: A high-fat diet (HFD)-induced mouse model was used, recombinant protein, herein referred as “Irisin”, intraperitoneally administered for 4 weeks evaluate effects accumulation. Liver tissues were stained with Oil red O (ORO), (TG) total cholesterol (TC) contents measured serum homogenates. The expression autophagosome marker microtubule-associated protein 1 light chain 3 (LC3), autophagy receptor sequestosome-1 (SQSTM1/p62), initiation complex unc-51-like kinase (ULK1) lysosomal functional cathepsin B via Western blotting, transcription factor EB (TFEB) analyzed immunofluorescence autophagic changes. effect flux further evaluated palmitic acid-induced HepG2 cells by measuring degradation chloroquine (CQ), analyzing colocalization LC3 lysosome-associated (LAMP1). possible mechanism examined sirtuin (SIRT3) pathway validated using overexpression SIRT3 plasmid transfection or siRNA-mediated knockdown. Student’s t -test utilized statistical analysis. Results: Irisin significantly reduces mice fed HFD, accompanied enhanced hepatocyte upregulation pathway. In cells, attenuated accumulation, which partially dependent levels. Mechanistically, treatment upregulated phosphorylated AMP-activated (AMPK), inhibited mammalian target rapamycin (mTOR) activity, promoted TFEB nucleus translocation, increased expression, degradation, alleviated steatosis. No significant changes phosphorylation ULK1 hepatocytes observed. However, when siRNA used knock down , those reversed, exacerbated. Conclusions: Our findings highlight potential therapeutic modulating potentially providing novel management MASLD. Further research needed elucidate clinical applications this approach

Language: Английский

Citations

1
Irisin, Exercise, and COVID-19 DOI Creative Commons
Hugo Rodrigues Alves, Guilherme Schittine Bezerra Lomba, Cassiano Felippe Gonçalves-de-Albuquerque

et al.

Frontiers in Endocrinology, Journal Year: 2022, Volume and Issue: 13

Published: June 17, 2022

Muscle and adipose tissue produce irisin during exercise. Irisin is thermogenic adipomyokine, improves glucose lipid metabolism, ameliorates the effects of obesity-driven inflammation, metabolic syndrome, diabetes. In addition, exercise-induced activates anti-inflammatory pathways may play an essential role in improving outcomes inflammatory conditions, such as coronavirus disease (COVID-19). COVID-19 infection can activate different intracellular receptors modulate various course disease. The cytokine release storm (CRS) produced significant because it promotes context for systemic which increases risk mortality patients with severe acute respiratory syndrome 2 (SARS-CoV2). viral resulting organ damage stimulate mitogen-activated protein kinase(MAPK) toll-like receptor 4 (TLR4)/toll interleukin (TIR)-domain-containing adaptor (MyD88) while negatively modulating AMP-activated kinase (AMPK) pathway, leading to increased production. Exercise-induced counteract this modulation by decreasing Consequently, levels, found healthy patients, favor a better prognosis SARS-CoV2. This review aims explore molecular mechanisms underlying properties mitigating CRS preventing due

Language: Английский

Citations

31
Adipose–Muscle crosstalk in age-related metabolic disorders: The emerging roles of adipo-myokines DOI
Penghua Fang,

Yuqing She,

Mei Yu

et al.

Ageing Research Reviews, Journal Year: 2022, Volume and Issue: 84, P. 101829 - 101829

Published: Dec. 20, 2022

Language: Английский

Citations

30