Role of membrane curvature on the activation/deactivation of Carnitine Palmitoyltransferase 1A: A coarse grain molecular dynamic study

Frigini, Ezequiel N.; Barrera, Exequiel; Pantano, Sergio; Porasso, Rodolfo D.

doi:10.1016/j.bbamem.2019.183094

Cited by 13 publications

(13 citation statements)

References 54 publications

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“…And PGC-1a acts as a key regulator of mitochondrial biogenesis and function, PPARa is involved in regulating fatty acid and cholesterol metabolism, and CPT 1A is an enzyme that is anchored to the outer mitochondrial membrane (OMM), and it regulates the passage of fatty acids into the mitochondria and interferes with boxidation of long-chain fatty acids. These three factors play an important role in the occurrence of fatty acid oxidation (38)(39)(40). So, these three factors were tested and shown in Figure 7.…”

Section: Discussionmentioning

confidence: 99%

Madecassoside Inhibits Body Weight Gain via Modulating SIRT1-AMPK Signaling Pathway and Activating Genes Related to Thermogenesis

et al. 2021

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BackgroundPre-clinical research studies have shown that Madecassoside (MA) has favorable therapeutic effects on arthritis, acne, vitiligo and other diseases. However, the effects of MA on obesity have not yet been studied. This study mainly aimed to investigate the effects of MA in protecting against obesity and its underlying mechanism in reducing obesity.MethodsObese diabetic KKay/TaJcl mice model was adopted to the study. The body weight of all animals was recorded daily, and the blood glucose, blood lipid, and serum aminotransferase levels were examined, respectively. The expression of P-AMPK, SIRT1, P-LKB1, P-ACC, and P-HSL in abdominal fat, mesenteric fat, and epididymal fat was measured by western blotting, and the levels of PPARα, CPT1a, PGC-1α, UCP-1, Cidea, Cox7a1, and Cox8b were examined by real-time quantitative PCR (RT-qPCR).ResultsThe results revealed that the body weight of the mice in MA group was significantly reduced, and the body mass index (BMI) showed significant difference between the two groups after 8 weeks of MA treatment. Further research revealed that it affected the mesenteric fat and epididymis fat by activating SIRT1/AMPK signaling pathway, and then promoted fatty acid oxidation of epididymal fat (PPARα ↑, CPT1a↑, and PGC-1α↑). Last but not the least, it also promoted the expression of UCP-1 and stimulated thermoregulatory genes (Cidea, Cox7a1, and Cox8b) in brown fat and mesenteric fat.ConclusionsTaken together, these findings suggest that MA can inhibit the weight gain in obese diabetic mice, and reduce triglyceride levels, inhibit lipogenesis of mesenteric fat, promote epididymal fat lipolysis and fatty acid oxidation. Furthermore, MA treatment might promote mesenteric fat browning and activate mitochondrial function in brown fat as well as mesenteric fat.

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Section: Discussionmentioning

confidence: 99%

Madecassoside Inhibits Body Weight Gain via Modulating SIRT1-AMPK Signaling Pathway and Activating Genes Related to Thermogenesis

et al. 2021

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“…26 On the other hand, it is worth mentioning that some cationic peptides as polymyxins, for instance, exhibit toxic effects even at relatively low dosages, limiting their practical application. 38 Nevertheless, this may not be true for the family of short peptides reported here. Previous reports by our group on acute and chronic toxicity in fish show that it appears only at concentrations greater than 150 mg/ mL.…”

Section: Introductionmentioning

confidence: 77%

The Mechanism of Antimicrobial Small-Cationic Peptides from Coarse-Grained Simulations

Frigini,

Porasso,

Beke-Somfai

et al. 2023

J. Chem. Inf. Model.

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Antimicrobial cationic peptides (AMPs) are excellent candidates for use as therapeutic antimicrobial agents. Among them, short peptides possessing sequences of 9–11 amino acids have some advantages over long-sequence peptides. However, one of the main limitations of short peptides is that their mechanism of action at the molecular level is not well-known. In this article, we report a model based on multiscale molecular dynamics simulations of short peptides interacting with vesicles containing palmitoyl-oleoyl-phosphatidylglycerol (POPG)/palmitoyl-oleoyl-phosphatidylethanolamine (POPE). Simulations using this approach have allowed us to understand the different behaviors of peptides with antimicrobial activity with respect to those that do not produce this effect. We found remarkable agreement with a series of experimental results directly supporting our model. Moreover, these results allow us to understand the mechanism of action at the molecular level of these short peptides. Our simulations suggest that mechanical inhomogeneities appear in the membrane, promoting membrane rupture when a threshold concentration of peptides adsorbed on the membrane is achieved. These results explain the high structural demand for these peptides to maintain a delicate balance between the affinity for the bilayer surface, a low peptide–peptide repulsion (in order to reach the threshold concentration), and an acceptable tendency to penetrate into the bilayer. This mechanism is different from those proposed for peptides with long amino acid sequences. Such information is very useful from the medicinal chemistry point of view for the design of new small antimicrobial peptides.

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“…The data regarding the CPT1A levels of expression and activity and rate of mitochondrial FAO are controversial and greatly depend on the model system used, FFA concentration, and other experimental conditions [68,69]. To explain these differences, several mechanisms have been suggested: (1) the levels of malonyl-CoA are variable and depend on the ratio of ACC/MCD proteins; (2) the physical properties of the mitochondrial membrane could change the sensitivity of CPT1A to malonyl-CoA [70]; and (3) the available pool of FFAs and other lipid intermediates could activate different transcription factors responsible for FA de novo synthesis, uptake, transport, and oxidation [71,72].…”

Section: Figurementioning

confidence: 99%

Mitochondrial Lipid Homeostasis at the Crossroads of Liver and Heart Diseases

Dabravolski

Bezsonov

Baig

et al. 2021

IJMS

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The prevalence of NAFLD (non-alcoholic fatty liver disease) is a rapidly increasing problem, affecting a huge population around the globe. However, CVDs (cardiovascular diseases) are the most common cause of mortality in NAFLD patients. Atherogenic dyslipidemia, characterized by plasma hypertriglyceridemia, increased small dense LDL (low-density lipoprotein) particles, and decreased HDL-C (high-density lipoprotein cholesterol) levels, is often observed in NAFLD patients. In this review, we summarize recent genetic evidence, proving the diverse nature of metabolic pathways involved in NAFLD pathogenesis. Analysis of available genetic data suggests that the altered operation of fatty-acid β-oxidation in liver mitochondria is the key process, connecting NAFLD-mediated dyslipidemia and elevated CVD risk. In addition, we discuss several NAFLD-associated genes with documented anti-atherosclerotic or cardioprotective effects, and current pharmaceutical strategies focused on both NAFLD treatment and reduction of CVD risk.

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Role of membrane curvature on the activation/deactivation of Carnitine Palmitoyltransferase 1A: A coarse grain molecular dynamic study

Cited by 13 publications

References 54 publications

Madecassoside Inhibits Body Weight Gain via Modulating SIRT1-AMPK Signaling Pathway and Activating Genes Related to Thermogenesis

Madecassoside Inhibits Body Weight Gain via Modulating SIRT1-AMPK Signaling Pathway and Activating Genes Related to Thermogenesis

The Mechanism of Antimicrobial Small-Cationic Peptides from Coarse-Grained Simulations

Mitochondrial Lipid Homeostasis at the Crossroads of Liver and Heart Diseases

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