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Journal of Alzheimer's Disease Reports 2024[This corrects the article DOI: 10.3233/ADR-210026.].
[This corrects the article DOI: 10.3233/ADR-210026.].
PubMed: 38910944
DOI: 10.3233/ADR-249000 -
Journal of Alzheimer's Disease Reports 2024Despite intense investigations, no effective treatment is yet available to reduce plaques and protect memory and learning in patients with Alzheimer's disease (AD), the...
Identification of Cinnamein, a Component of Balsam of Tolu/Peru, as a New Ligand of PPARα for Plaque Reduction and Memory Protection in a Mouse Model of Alzheimer's Disease.
BACKGROUND
Despite intense investigations, no effective treatment is yet available to reduce plaques and protect memory and learning in patients with Alzheimer's disease (AD), the most common neurodegenerative disorder. Therefore, it is important to identify a non-toxic, but effective, treatment option for AD.
OBJECTIVE
Cinnamein, a nontoxic compound, is naturally available in Balsam of Peru and Tolu Balsam. We examined whether cinnamein treatment could decrease plaques and improve cognitive functions in mouse model of AD.
METHODS
We employed analysis, time-resolved fluorescence energy transfer assay, thermal shift assay, primary neuron isolation, western blot, immunostaining, immunohistochemistry, Barnes maze, T maze, and open field behavior.
RESULTS
Oral administration of cinnamein led to significant reduction in amyloid-β plaque deposits in the brain and protection of spatial learning and memory in mice. Peroxisome proliferator-activated receptor alpha (PPARα), a nuclear hormone receptor, is involved in plaque lowering and increase in hippocampal plasticity. While investigating underlying mechanisms, we found that cinnamein served as a ligand of PPARα. Accordingly, oral cinnamein upregulated the level of PPARα, but not PPARβ, in the hippocampus, and remained unable to decrease plaques from the hippocampus and improve memory and learning in mice lacking PPARα. While A disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) is one of the drivers of nonamyloidogenic pathway, transcription factor EB (TFEB) is considered as the master regulator of autophagy. Cinnamein treatment was found to upregulate both ADAM10 and TFEB in the brain of mice via PPARα.
CONCLUSIONS
Our results suggest that this balsam component may have therapeutic importance in AD.
PubMed: 38910936
DOI: 10.3233/ADR-230179 -
Scientific Reports Jun 2024Blood-brain barrier disruption is a critical pathological event in the progression of ischemic stroke (IS). Most studies regarding the therapeutic potential of neferine...
Blood-brain barrier disruption is a critical pathological event in the progression of ischemic stroke (IS). Most studies regarding the therapeutic potential of neferine (Nef) on IS have focused on neuroprotective effect. However, whether Nef attenuates BBB disruption during IS is unclear. We here used mice underwent transient middle cerebral artery occlusion (tMCAO) in vivo and bEnd.3 cells exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) injury in vitro to simulate cerebral ischemia. We showed that Nef reduced neurobehavioral dysfunction and protected brain microvascular endothelial cells and BBB integrity. Molecular docking, short interfering (Si) RNA and plasmid transfection results showed us that PGC-1α was the most binding affinity of biological activity protein for Nef. And verification experiments were showed that Nef upregulated PGC-1α expression to reduce mitochondrial oxidative stress and promote TJ proteins expression, further improves the integrity of BBB in mice. Intriguingly, our study showed that neferine is a natural PGC-1α activator and illustrated the mechanism of specific binding site. Furthermore, we have demonstrated Nef reduced mitochondria oxidative damage and ameliorates endothelial inflammation by inhibiting pyroptosis to improve BBB permeability through triggering a cascade reaction of PGC-1α via regulation of PGC-1α/NLRP3/GSDMD signaling pathway to maintain the integrity of BBB in ischemia/reperfusion injury.
Topics: Animals; Blood-Brain Barrier; Pyroptosis; Mice; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Ischemic Stroke; Endothelial Cells; Benzylisoquinolines; Male; Oxidative Stress; Mitochondria; Mice, Inbred C57BL; Disease Models, Animal; Neuroprotective Agents
PubMed: 38910141
DOI: 10.1038/s41598-024-64815-w -
Endocrine Journal Jun 2024Fibroblast growth factor (FGF) 21, a hormone produced by the liver, improves glucose and lipid metabolism. We recently demonstrated that the FGF21 gene (Fgf21) underwent...
Fibroblast growth factor (FGF) 21, a hormone produced by the liver, improves glucose and lipid metabolism. We recently demonstrated that the FGF21 gene (Fgf21) underwent DNA demethylation in the mouse liver via peroxisome proliferator-activated receptor (PPAR) α during the fetal to lactation periods. Furthermore, we found that the DNA methylation state of Fgf21 was involved in obesity in adult animals. In the present study, we analyzed the DNA methylation state of the FGF21 gene (FGF21) in obese patients using genomic DNA extracted from human monocytes and macrophages and investigated the pathophysiological significance of the FGF21 expression response to pemafibrate (PM), a PPARα ligand. We examined 67 patients with obesity stratified into in- and outpatient cohorts. A positive correlation was observed between serum FGF21 levels and triglyceride (TG) levels before PM administration. However, changes in serum FGF21 levels following PM administration did not correlate with the FGF21 DNA methylation rate, except at one CpG site. The body mass index (BMI) and serum TG levels positively correlated with the FGF21 DNA methylation rate, particularly at different CpG positions. A negative correlation was observed between absolute changes in serum FGF21 levels and the ratio of change in serum TG levels after PM administration. Collectively, these results indicate the potential of FGF21 DNA methylation as a surrogate indicator of BMI and serum TG levels, while absolute changes in serum FGF21 levels after PM administration may offer prognostic insights into the efficacy of reducing serum TG levels through PM administration.
PubMed: 38910123
DOI: 10.1507/endocrj.EJ23-0570 -
Meat Science Jun 2024The current study aimed to investigate the metabolic and microbial mechanisms behind the effects of dietary wheat levels on intramuscular fat (IMF) content in the psoas...
The current study aimed to investigate the metabolic and microbial mechanisms behind the effects of dietary wheat levels on intramuscular fat (IMF) content in the psoas major muscle (PM) of finishing pigs. Thirty-six barrows were arbitrarily assigned to two groups and fed with diets containing 25% or 55% wheat. Enhancing dietary wheat levels led to low energy states, resulting in reduced IMF content. This coincided with reduced serum glucose and low-density lipoprotein cholesterol levels. The AMP-activated protein kinase α2/sirtuin 1/peroxisome proliferator-activated receptor-γ coactivator 1α pathway may be activated by high-wheat diets, causing downregulation of adipogenesis and lipogenesis genes, and upregulation of lipolysis and gluconeogenesis genes. High-wheat diets decreased relative abundance of Lactobacillus and Coprococcus, whereas increased SMB53 proportion, subsequently decreasing colonic propionate content. Microbial glycolysis/gluconeogenesis, d-glutamine and D-glutamate metabolism, flagellar assembly, and caprolactam degradation were linked to IMF content. Metabolomic analysis indicated that enhancing dietary wheat levels promoted the protein digestion and absorption and affected amino acids and lipid metabolism. Enhancing dietary wheat levels reduced serum glucose and colonic propionate content, coupled with strengthened amino acid metabolism, contributing to the low energy states. Furthermore, alterations in microbial composition and propionate resulted from high-wheat diets were associated with primary bile acid biosynthesis, arachidonic acid metabolism, steroid hormone biosynthesis, and biosynthesis of unsaturated fatty acids, as well as IMF content. Colonic microbiota played a role in reducing IMF content through modulating the propionate-mediated peroxisome proliferators-activated receptor signaling pathway. In conclusion, body energy and gut microbiota balance collectively influenced lipid metabolism.
PubMed: 38909450
DOI: 10.1016/j.meatsci.2024.109574 -
Lipids in Health and Disease Jun 2024Overweight, often known as obesity, is the abnormal and excessive accumulation of fat that exposes the health of a person at risk by increasing the likelihood that they...
BACKGROUND
Overweight, often known as obesity, is the abnormal and excessive accumulation of fat that exposes the health of a person at risk by increasing the likelihood that they may experience many chronic conditions. Consequently, obesity has become a global health threat, presenting serious health issues, and attracting a lot of attention in the healthcare profession and the scientific community.
METHOD
This study aims to explore the anti-adipogenic properties of 7-MEGA™ in an attempt to address obesity, using both in vitro and in vivo research. The effects of 7MEGA™ at three distinct concentrations were investigated in obese mice who were given a high-fat diet (HFD) and 3T3-L1 adipocytes.
RESULTS
7MEGA™ decreased the total fat mass, overall body weight, and the perirenal and subcutaneous white adipose tissue (PWAT and SWAT) contents in HFD mice. Additionally, 7MEGA™ showed promise in improving the metabolic health of individuals with obesity and regulate the levels of insulin hormone, pro-inflammatory cytokines and adipokines. Furthermore, Peroxisome proliferator-activated receptors (PPAR) α and γ, Uncoupling Protein 1 (UCP-1), Sterol Regulatory Element-Binding Protein 1 (SREBP-1), Fatty Acid-Binding Protein 4 (FABP4), Fatty Acid Synthase (FAS), Acetyl-CoA Carboxylase (ACC), Stearoyl-CoA Desaturase-1 (SCD-1) and CCAAT/Enhancer-Binding Protein (C/EBPα) were among the adipogenic regulators that 7MEGA™ could regulate.
CONCLUSION
In summary, this study uncovered that 7MEGA™ demonstrates anti-adipogenic and anti-obesity effects, suggesting its potential in combating obesity.
Topics: Animals; Diet, High-Fat; Adipogenesis; Obesity; Mice; 3T3-L1 Cells; Adipocytes; Mice, Inbred C57BL; Male; PPAR gamma; Sterol Regulatory Element Binding Protein 1; Stearoyl-CoA Desaturase; Mice, Obese; Fatty Acid-Binding Proteins; Adipokines; Anti-Obesity Agents; Uncoupling Protein 1; Adipose Tissue, White; CCAAT-Enhancer-Binding Proteins
PubMed: 38909257
DOI: 10.1186/s12944-024-02175-0 -
Biomedicine & Pharmacotherapy =... Jun 2024Sarcopenia is an aging-related skeletal disease characterized by decreased muscle mass, strength, and physical function, severely affecting the quality of life (QoL) of... (Review)
Review
Sarcopenia is an aging-related skeletal disease characterized by decreased muscle mass, strength, and physical function, severely affecting the quality of life (QoL) of the elderly population. Sirtuin 1 (SIRT1), as a nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylases, has been reported to participate in various aging-related signaling pathways and exert protective effect on many human diseases. SIRT1 functioned as an important role in the occurrence and progression of sarcopenia through regulating key pathways related to protein homeostasis, apoptosis, mitochondrial dysfunction, insulin resistance and autophagy in skeletal muscle, including SIRT1/Forkhead Box O (FoxO), AMP-activated protein kinase (AMPK)/SIRT1/nuclear factor κB (NF-κB), SIRT1/p53, AMPK/SIRT1/peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), and SIRT1/live kinase B1 (LKB1)/AMPK pathways. However, the specific mechanisms of these processes have not been fully illuminated. Currently, several SIRT1-mediated interventions on sarcopenia have been preliminarily developed, such as SIRT1 activator polyphenolic compounds, exercising and calorie restriction. In this review, we summarized the predominant mechanisms of SIRT1 involved in sarcopenia and therapeutic modalities targeting the SIRT1 signaling pathways for the prevention and prognosis of sarcopenia.
PubMed: 38908209
DOI: 10.1016/j.biopha.2024.116917 -
Journal of Animal Science Jan 2024Mulberry leaves (MLs) are an unconventional feed with fiber and various active ingredients, and are acknowledged as likely to regulate lipid metabolism, while the...
Mulberry leaves (MLs) are an unconventional feed with fiber and various active ingredients, and are acknowledged as likely to regulate lipid metabolism, while the molecular mechanism remains undefined. Therefore, our objective was to define the role of MLs on the overall lipid metabolism. We conducted a feeding experiment of three groups on growing mutton sheep fed with dried mulberry leaves (DMLs), with fermented mulberry leaves (FMLs), or without MLs (as control). Analyses of transcriptome and widely target lipids demonstrated the addition of MLs triggered big perturbations in genes and metabolites related to glycerolipid, phospholipid, ether lipid, and sphingolipid metabolism. Additionally, the variations of the above lipids in the treatment of MLs possibly facilitate immunity enhancement of growing mutton sheep via the activation of complement and coagulation cascades. Furthermore, treatments with MLs could expedite proceedings of lipid degradation and fatty acid β oxidation in mitochondria, thereby to achieve the effect of lipid reduction. Besides, added DMLs also fuel fatty acid β-oxidation in peroxisomes and own much stronger lipolysis than added FMLs, possibly attributed to high fiber content in DMLs. These findings establish the novel lipid-lowering role and immune protection of MLs, which lays the foundation for the medicinal application of MLs.
Topics: Animals; Morus; Lipid Metabolism; Plant Leaves; Sheep; Fatty Acids; Animal Feed; Diet; Dietary Supplements; Oxidation-Reduction
PubMed: 38908013
DOI: 10.1093/jas/skae076 -
Biomedicine & Pharmacotherapy =... Jun 2024Obesity aggravates ferroptosis, and vitamin D (VD) may inhibit ferroptosis. We hypothesized that weight reduction and/or calcitriol administration have benefits against...
Obesity aggravates ferroptosis, and vitamin D (VD) may inhibit ferroptosis. We hypothesized that weight reduction and/or calcitriol administration have benefits against the sepsis-induced liver redox imbalance and ferroptosis in obese mice. Mice were fed a high-fat diet for 11 weeks, then half of the mice continued to consume the diet, while the other half were transferred to a low-energy diet for 5 weeks. After feeding the respective diets for 16 weeks, sepsis was induced by cecal ligation and puncture (CLP). Septic mice were divided into four experimental groups: OS group, obese mice injected with saline; OD group, obese mice with calcitriol; WS group, weight-reduction mice with saline; and WD group, weight-reduction mice with calcitriol. Mice in the respective groups were euthanized at 12 or 24 h after CLP. Results showed that the OS group had the highest inflammatory mediators and lipid peroxide levels in the liver. Calcitriol treatment reduced iron content, enhanced the reduced glutathione/oxidized glutathione ratio, upregulated nuclear factor erythroid 2-related factor 2, ferroptosis-suppressing protein 1, and solute carrier family 7 member 11 expression levels. Also, mitochondrion-associated nicotinamide adenine dinucleotide phosphate oxidase 1, peroxisome proliferator-activated receptor-γ coactivator 1, hypoxia-inducible factor-1α, and heme oxidase-1 expression levels increased in the late phase of sepsis. These results were not noted in the WS group. These findings suggest that calcitriol treatment elicits a more-balanced glutathione redox status, alleviates liver ferroptosis, and enhances mitochondrial biogenesis-associated gene expressions. Weight reduction alone had minimal influences on liver ferroptosis and mitochondrial biogenesis in obese mice with sepsis.
PubMed: 38906016
DOI: 10.1016/j.biopha.2024.116926