Endoplasmic reticulum stress: bridging inflammation and obesity-associated adipose tissue

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Апрель 4, 2024

Obesity presents a significant global health challenge, increasing the susceptibility to chronic conditions such as diabetes, cardiovascular disease, and hypertension. Within context of obesity, lipid metabolism, adipose tissue formation, inflammation are intricately linked endoplasmic reticulum stress (ERS). ERS modulates insulin signaling, inflammation, well cell proliferation death through unfolded protein response (UPR) pathway. Serving crucial nexus, bridges functionality inflammatory response. In this review, we comprehensively elucidate mechanisms by which impacts function in aiming offer insights into targeting for ameliorating metabolic dysregulation obesity-associated diseases hyperlipidemia, hypertension, fatty liver, type 2 diabetes.

Язык: Английский

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Irisin alleviates hepatic steatosis by activating the autophagic SIRT3 pathway

Chinese Medical Journal, Год журнала: 2025, Номер unknown

Опубликована: Фев. 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

Язык: Английский

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Investigating the Interplay between Mitophagy and Diabetic Neuropathy: Uncovering the hidden secrets of the disease pathology

Pharmacological Research, Год журнала: 2024, Номер 208, С. 107394 - 107394

Опубликована: Сен. 3, 2024

Mitophagy, the cellular process of selectively eliminating damaged mitochondria, plays a crucial role in maintaining metabolic balance and preventing insulin resistance, both key factors type 2 diabetes mellitus (T2DM) development. When mitophagy malfunctions diabetic neuropathy, it triggers cascade disruptions, including reduced energy production, increased oxidative stress, cell death, ultimately leading to various complications. Thus, targeting enhance may have emerged as promising therapeutic strategy for T2DM its Notably, plant-derived compounds with β-cell protective mitophagy-stimulating properties offer potential novel agents. This review highlights intricate mechanisms linking dysfunction complications, particularly elucidating interventions this debilitating disease.

Язык: Английский

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Effects of induced molting on lipid accumulation in liver of aged laying hens

Poultry Science, Год журнала: 2025, Номер 104(4), С. 104941 - 104941

Опубликована: Фев. 22, 2025

Язык: Английский

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Ferroptosis contributes to the progression of female-specific neoplasms, from breast cancer to gynecological malignancies in a manner regulated by non-coding RNAs: Mechanistic implications

Non-coding RNA Research, Год журнала: 2024, Номер 9(4), С. 1159 - 1177

Опубликована: Май 20, 2024

Ferroptosis, a recently identified type of non-apoptotic cell death, triggers the elimination cells in presence lipid peroxidation and an iron-dependent manner. Indeed, ferroptosis-stimulating factors have ability suppressing antioxidant capacity, leading to accumulation reactive oxygen species (ROS) subsequent oxidative death cells. Ferroptosis is involved pathophysiological basis different maladies, such as multiple cancers, among which female-oriented malignancies attracted much attention recent years. In this context, it has also been unveiled that non-coding RNA transcripts, including microRNAs, long RNAs, circular RNAs regulatory interconnections with ferroptotic flux, controls pathogenic development diseases. Furthermore, potential employing these transcripts therapeutic targets during onset female-specific neoplasms modulate ferroptosis become research hotspot; however, molecular mechanisms functional alterations still require further investigation. The current review comprehensively highlights its association focus on how crosstalk affects pathogenesis malignancies, from breast cancer ovarian, cervical, endometrial neoplasms, suggesting novel decelerate even block expansion tumors.

Язык: Английский

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Autophagy and the peroxisome proliferator-activated receptor signaling pathway: A molecular ballet in lipid metabolism and homeostasis

Molecular and Cellular Biochemistry, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Язык: Английский

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Cell Homeostasis or Cell Death—The Balancing Act Between Autophagy and Apoptosis Caused by Steatosis-Induced Endoplasmic Reticulum (ER) Stress

Cells, Год журнала: 2025, Номер 14(6), С. 449 - 449

Опубликована: Март 18, 2025

Metabolic-dysfunction-associated steatotic liver disease (MASLD) is a prevalent condition with potential progression to cirrhosis and impaired regeneration post-resection. A key mechanism underlying lipotoxicity endoplasmic reticulum (ER) stress, particularly the activation of unfolded protein response (UPR). This study investigates interplay between lipid accumulation, cellular outcomes, focusing on balance autophagy apoptosis. We cultured primary human hepatocytes (PHH) in free fatty acid (FFA)-enriched medium for 120 h, assessing metabolism, expression selected UPR markers. Additionally, we investigated effects load cell activity growth proliferating HepG2 cells. observed that FFA uptake consistently induced ER shifting responses toward apoptosis under high loads. Donor-specific differences were evident, storage, excretion, sensitivity lipotoxicity. Some donors exhibited limited triglyceride (TAG) storage leading an excess whose metabolic fate remains unclear. Proliferation was more sensitive accumulation than overall activity, even low concentrations impairing growth, highlighting vulnerability regenerative processes steatosis. The elucidates how stress pathways, such as PERK-CHOP IRE1α-JNK, are differentially activated overload, tipping severe cases. repair mechanisms, autophagy, further emphasizes critical role determining hepatocyte fate. donor-dependent variability highlights need personalized strategies mitigate lipotoxic enhance steatosis-related conditions.

Язык: Английский

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Targeting autophagy can synergize the efficacy of immune checkpoint inhibitors against therapeutic resistance: New promising strategy to reinvigorate cancer therapy

Heliyon, Год журнала: 2024, Номер 10(18), С. e37376 - e37376

Опубликована: Сен. 1, 2024

Язык: Английский

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Accumulation of Non-Pathological Liver Fat Is Associated with the Loss of Glyoxalase I Activity in Humans

Metabolites, Год журнала: 2024, Номер 14(4), С. 209 - 209

Опубликована: Апрель 7, 2024

The underlying molecular mechanisms for the development of non-alcoholic fatty liver (NAFL) and its progression to advanced diseases remain elusive. Glyoxalase 1 (Glo1) loss, leading elevated methylglyoxal (MG) dicarbonyl stress, has been implicated in various diseases, including obesity-related conditions. This study aimed investigate changes glyoxalase system individuals with non-pathological fat. Liver biopsies were obtained from 30 a narrow range BMI (24.6–29.8 kg/m2). Whole-body insulin sensitivity was assessed using HOMA-IR. analyzed total triglyceride content, Glo1 Glo2 mRNA, protein expression, activity. Liquid chromatography–tandem mass spectrometry determined content oxidation glycation biomarkers. activity showed an inverse correlation HOMA-IR but not BMI. Despite reduced activity, no associations found dicarbonyls or markers. A sex dimorphism observed Glo1, females exhibiting significantly lower expression higher MG-H1 compared males. demonstrates that increasing fat, even within range, is associated

Язык: Английский

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A new perspective on liver diseases: focusing on the mitochondria-associated endoplasmic reticulum membranes

Pharmacological Research, Год журнала: 2024, Номер unknown, С. 107409 - 107409

Опубликована: Сен. 1, 2024

Язык: Английский

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