SIRT3 Modulates Endothelial Mitochondrial Redox State during Insulin Resistance

Martino, Elisa; Balestrieri, Anna; Anastasio, Camilla; Maione, Martina; Mele, Luigi; Cautela, Domenico; Campanile, Giuseppe; Balestrieri, Maria Luisa

doi:10.3390/antiox11081611

“…The improved lipid metabolism conferred by LR may be related to reduce ERS. In the other two studies, LR also improves lipid metabolism by regulating other pathways, which is consistent with this study [ 27 , 28 ].…”

Section: Discussionsupporting

confidence: 92%

Mechanism of GLP-1 Receptor Agonists-Mediated Attenuation of Palmitic Acid-Induced Lipotoxicity in L6 Myoblasts

Kong

¹

,

Gao

²

,

Xie

³

et al. 2022

BioMed Research International

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Object. L6 cells were cultured to explore the possible mechanism underlying the improvement of insulin resistance by Liraglutide (LR). Methods. Cells were divided into 5 groups—control, high-fat, 10 nmol/L LR + 0.6 mmol/L palmitic acid (PA) (10LR), 100 nmol/L LR + 0.6 mmol/L PA (100LR), and 1000 nmol/L LR + 0.6 mmol/L PA (1000LR). CCK-8 method to detect cell viability, GPO-PAP enzymatic method to detect intracellular triglyceride content, and reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and western blotting methods to detect fatty acid translocase CD36 (FAT/CD36) and fatty acid binding protein 4 (FABP4) in L6 cells, glucose-regulated protein 78 (GRP78), glucose transporter 4 (GLUT4) expression at the mRNA and protein levels, respectively, were performed. Results. We found that after PA intervention for 24 h, the cell viability decreased significantly; the cell viability of the LR group was higher than that of the high-fat group ( P < 0.01 ). After PA intervention, compared with those in the high-fat group, GRP-78, FAT/CD36, FABP4 mRNA ((4.36 ± 0.32 vs. 8.15 ± 0.35 ); ( 1.00 ± 0.04 vs. 2.46 ± 0.08 ); ( 2.88 ± 0.55 vs. 8.29 ± 0.52 ), P < 0.01 ) and protein (( 3338.13 ± 333.15 vs. 4963.98 ± 277.29 ); ( 1978.85 ± 124.24 vs. 2676.07 ± 100.64 ); ( 3372.00 ± 219.84 vs. 6083.20 ± 284.70 ), both P < 0.01 ) expression decreased in the LR group. The expression levels of GLUT4 mRNA (( 0.75 ± 0.04 vs. 0.34 ± 0.03 ), P < 0.01 ) and protein (( 3443.71 ± 191.89 vs. 2137.79 ± 118.75 ), P < 0.01 ) increased. Conclusion. Therefore, we conclude that LR can reverse PA-induced cell inactivation and lipid deposition, which may be related to the change in GRP-78, FAT/CD36, FABP4, GLUT4, and other factors.

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“…Bioactive compounds of milk, especially buffalo milk, have been described as epi-nutrient for cancer prevention. In SW480 and SW620 CRC cells δ-valerobetaine, a constitutive milk metabolite with antioxidant, anti-inflammatory, and anti-diabetic activities, impaired cell viability in a time-dependent way, blocked cell cycle at G2/M increasing the expression of cyclin A and cyclin B protein [ 14 , 17 , 47 ]. Caspase-3 activation, together with loss in mitochondrial membrane potential and SIRT3 downmodulation, enhanced apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Milk Exosomal miR-27b Worsen Endoplasmic Reticulum Stress Mediated Colorectal Cancer Cell Death

Martino

¹

,

Balestrieri

²

,

Mele

³

et al. 2022

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The relationship between dietary constituents and the onset and prevention of colorectal cancer (CRC) is constantly growing. Recently, the antineoplastic profiles of milk and whey from Mediterranean buffalo (Bubalus bubalis) have been brought to attention. However, to date, compared to cow milk, the potential health benefits of buffalo milk exosome-miRNA are still little explored. In the present study, we profiled the exosomal miRNA from buffalo milk and investigated the possible anticancer effects in CRC cells, HCT116, and HT-29. Results indicated that buffalo milk exosomes contained higher levels of miR-27b, miR-15b, and miR-148a compared to cow milk. Mimic miR-27b transfection in CRC cells induced higher cytotoxic effects (p < 0.01) compared to miR-15b and miR-148a. Moreover, miR-27b overexpression in HCT116 and HT-29 cells (miR-27b+) induced apoptosis, mitochondrial reactive oxygen species (ROS), and lysosome accumulation. Exposure of miR-27b+ cells to the bioactive 3kDa milk extract aggravated the apoptosis rate (p < 0.01), mitochondrial stress (p < 0.01), and advanced endoplasmic reticulum (ER) stress (p < 0.01), via PERK/IRE1/XBP1 and CHOP protein modulation (p < 0.01). Moreover, GSK2606414, the ER-inhibitor (ER-i), decreased the apoptosis phenomenon and XBP1 and CHOP modulation in miR-27b+ cells treated with milk (p < 0.01 vs. miR-27b++Milk), suggesting the ER stress as a cell-death-aggravating mechanism. These results support the in vitro anticancer activity of 3kDa milk extract and unveil the contribution of miR-27b in the promising beneficial effect of buffalo milk in CRC prevention.

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“…Additionally, recent data showed that δ-valerobetaine also protected ECs against PA-induced insulin resistance (IR) by limiting the inhibitory phosphorylation of IRS1 and restoring phosphorylated Akt expression levels. In particular, δ-valerobetaine reduced oxidative stress and cytokine levels, restored the expression levels of mitochondrial sirtuin 3, and attenuated pyroptosis and autophagy [ 32 ]. Further studies are undoubtedly necessary for a deeper understanding of biological effects caused by bioactive compounds identified in the milk and/or their mixtures in the prevention of EC inflammation.…”

Section: Discussionmentioning

confidence: 99%

Breed and Feeding System Impact the Bioactive Anti-Inflammatory Properties of Bovine Milk

Salzano

¹

,

Meo

²

,

Bifulco

³

et al. 2022

IJMS

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In the present study, we aimed at assessing the influence of breed and feeding system on the bovine milk profile of betaines and carnitines and milk capacity in counteracting the inflammatory endothelial cell (EC) damage induced by interleukin (IL)-6. In the first experimental design, two breeds were chosen (Holstein vs. Modicana) to investigate the biomolecule content and antioxidant capacity in milk and dairy products. In the second experimental design, two feeding systems (pasture vs. total mixed ratio) were tested only in Holstein to evaluate the possible effect on the functional profile of milk and dairy products. Finally, the bulk milk from the two experimental designs was used to evaluate the efficacy of preventing IL-6-induced endothelial inflammatory damage. Results showed that Modicana milk and whey had higher biomolecule content and antioxidant activity compared to Holstein milk (p < 0.01). Milk from Holstein fed TMR showed higher concentration of γ-butyrobetaine, δ-valerobetaine (p < 0.01), and l-carnitine (p < 0.05). Similarly, whey from Holstein fed TMR also showed higher content of δ-valerobetaine, glycine betaine, l-carnitine, and acetyl-l-carnitine (p < 0.01) compared to the Holstein fed pasture. Conversely, the antioxidant activity of milk and dairy products was not affected by the feeding system. In ECs, all milk samples reduced the IL-6-induced cytokine release, as well as the accumulation of reactive oxygen species (ROS) and the induction of cell death, with the most robust effect elicited by Modicana milk (p < 0.01). Overall, Modicana milk showed a higher content of biomolecules and antioxidant activity compared to Holstein, suggesting that the breed, more than the feeding system, can positively affect the health-promoting profile of dairy cattle milk.

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SIRT3 Modulates Endothelial Mitochondrial Redox State during Insulin Resistance

Cited by 16 publications

References 45 publications

Mechanism of GLP-1 Receptor Agonists-Mediated Attenuation of Palmitic Acid-Induced Lipotoxicity in L6 Myoblasts

Mechanism of GLP-1 Receptor Agonists-Mediated Attenuation of Palmitic Acid-Induced Lipotoxicity in L6 Myoblasts

Milk Exosomal miR-27b Worsen Endoplasmic Reticulum Stress Mediated Colorectal Cancer Cell Death

Breed and Feeding System Impact the Bioactive Anti-Inflammatory Properties of Bovine Milk

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