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Journal of Obesity & Metabolic Syndrome May 2024AMP-activated protein kinase (AMPK) is a key enzyme for cellular energy homeostasis and improves metabolic disorders. Brown and beige adipose tissues exert thermogenesis...
BACKGROUND
AMP-activated protein kinase (AMPK) is a key enzyme for cellular energy homeostasis and improves metabolic disorders. Brown and beige adipose tissues exert thermogenesis capacities to dissipate energy in the form of heat. Here, we investigated the beneficial effects of the antioxidant alpha-lipoic acid (ALA) in menopausal obesity and the underlying mechanisms.
METHODS
Female Wistar rats (8 weeks old) were subjected to bilateral ovariectomy (Ovx) and divided into four groups: Sham (n=8), Ovx (n=11), Ovx+ALA2 (n=10), and Ovx+ALA3 (n=6) (ALA 200 and 300 mg/kg/day, respectively; gavage) for 8 weeks. 3T3-L1 cells were used for study.
RESULTS
Rats receiving ALA2 and ALA3 treatment showed significantly lower levels of body weight and white adipose tissue (WAT) mass than those of the Ovx group. ALA improved plasma lipid profiles including triglycerides, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. Hematoxylin & eosin staining of inguinal WAT showed that ALA treatment reduced Ovx-induced adipocyte size and enhanced uncoupling protein 1 (UCP1) expression. Moreover, plasma levels of irisin were markedly increased in ALA-treated Ovx rats. Protein expression of brown fat-specific markers including UCP1, PRDM16, and CIDEA was downregulated by Ovx but markedly increased by ALA. Phosphorylation of AMPK, its downstream acetyl-CoA carboxylase, and its upstream LKB1 were all significantly increased by ALA treatment. In 3T3-L1 cells, administration of ALA (100 and 250 μM) reduced lipid accumulation and enhanced oxygen consumption and UCP1 protein expression, while inhibition of AMPK by dorsomorphin (5 μM) significantly reversed these effects.
CONCLUSION
ALA improves estrogen deficiency-induced obesity via browning of WAT through AMPK signaling.
PubMed: 38699871
DOI: 10.7570/jomes23048 -
PeerJ 2024Exogenous use of potential organic compounds through different modes is a promising strategy for the induction of water stress tolerance in crop plants for better yield.
CONTEXT
Exogenous use of potential organic compounds through different modes is a promising strategy for the induction of water stress tolerance in crop plants for better yield.
AIMS
The present study aimed to explore the potential role of alpha-lipoic acid (ALA) in inducing water stress tolerance in mungbean lines when applied exogenously through various modes.
METHODS
The experiment was conducted in a field with a split-plot arrangement, having three replicates for each treatment. Two irrigation regimes, including normal and reduced irrigation, were applied. The plants allocated to reduced irrigation were watered only at the reproductive stage. Three levels of ALA (0, 0.1, 0.15 mM) were applied through different modes (seed priming, foliar or priming+foliar).
KEY RESULTS
ALA treatment through different modes manifested higher growth under reduced irrigation (water stress) and normal irrigation. Compared to the other two modes, the application of ALA as seed priming was found more effective in ameliorating the adverse impacts of water stress on growth and yield associated with their better content of leaf photosynthetic pigments, maintenance of plant water relations, levels of non-enzymatic antioxidants, improved activities of enzymatic antioxidants, and decreased lipid peroxidation and HO levels. The maximum increase in shoot fresh weight (29% and 28%), shoot dry weight (27% and 24%), 100-grain weight (24% and 23%) and total grain yield (20% and 21%) in water-stressed mungbean plants of line 16003 and 16004, respectively, was recorded due to ALA seed priming than other modes of applications.
CONCLUSIONS
Conclusively, 0.1 and 0.15 mM levels of ALA as seed priming were found to reduce the adverse impact of water stress on mungbean yield that was associated with improved physio-biochemical mechanisms.
IMPLICATIONS
The findings of the study will be helpful for the agriculturalists working in arid and semi-arid regions to obtain a better yield of mungbean that will be helpful to fulfill the food demand in those areas to some extent.
Topics: Vigna; Thioctic Acid; Antioxidants; Photosynthesis; Droughts; Plant Leaves; Dehydration; Chlorophyll; Lipid Peroxidation
PubMed: 38699184
DOI: 10.7717/peerj.17191 -
Journal of Nanobiotechnology Apr 2024Osteoporosis is a highly prevalent metabolic disease characterized by low systemic bone mass and deterioration of bone microarchitecture, resulting in reduced bone...
Osteoporosis is a highly prevalent metabolic disease characterized by low systemic bone mass and deterioration of bone microarchitecture, resulting in reduced bone strength and increased fracture risk. Current treatment options for osteoporosis are limited by factors such as efficacy, cost, availability, side effects, and acceptability to patients. Gold nanoparticles show promise as an emerging osteoporosis therapy due to their osteogenic effects and ability to allow therapeutic delivery but have inherent constraints, such as low specificity and the potential for heavy metal accumulation in the body. This study reports the synthesis of ultrasmall gold particles almost reaching the Ångstrom (Ång) dimension. The antioxidant alpha-lipoic acid (LA) is used as a dispersant and stabilizer to coat Ångstrom-scale gold particles (AuÅPs). Alendronate (AL), an amino-bisphosphonate commonly used in drug therapy for osteoporosis, is conjugated through LA to the surface of AuÅPs, allowing targeted delivery to bone and enhancing antiresorptive therapeutic effects. In this study, alendronate-loaded Ångstrom-scale gold particles (AuÅPs-AL) were used for the first time to promote osteogenesis and alleviate bone loss through regulation of the WNT signaling pathway, as shown through in vitro tests. The in vivo therapeutic effects of AuÅPs-AL were demonstrated in an established osteoporosis mouse model. The results of Micro-computed Tomography, histology, and tartrate-resistant acid phosphatase staining indicated that AuÅPs-AL significantly improved bone density and prevented bone loss, with no evidence of nanoparticle-associated toxicity. These findings suggest the possible future application of AuÅPs-AL in osteoporosis therapy and point to the potential of developing new approaches for treating metabolic bone diseases using Ångstrom-scale gold particles.
Topics: Animals; Alendronate; Thioctic Acid; Gold; Osteoporosis; Mice; Metal Nanoparticles; Female; Osteogenesis; Mice, Inbred C57BL; Bone Density Conservation Agents; Particle Size
PubMed: 38689294
DOI: 10.1186/s12951-024-02466-9 -
Gynecological Endocrinology : the... Dec 2024To evaluate the effects of alpha lipoic acid (ALA) on hormonal and metabolic parameters in a group of overweight/obese Polycystic Ovary Syndrome (PCOS) patients.
Alpha lipoic acid administration improved both peripheral sensitivity to insulin and liver clearance of insulin reducing potential risk of diabetes and nonalcoholic fatty liver disease in overweight/obese PCOS patients.
OBJECTIVE
To evaluate the effects of alpha lipoic acid (ALA) on hormonal and metabolic parameters in a group of overweight/obese Polycystic Ovary Syndrome (PCOS) patients.
METHODS
This was a retrospective study in which thirty-two overweight/obese patients with PCOS ( = 32) not requiring hormonal treatment were selected from the database of the ambulatory clinic of the Gynecological Endocrinology Center at the University of Modena and Reggio Emilia, Italy. The hormonal profile, routine exams and insulin and C-peptide response to oral glucose tolerance test (OGTT) were evaluated before and after 12 weeks of complementary treatment with ALA (400 mg/day). Hepatic Insulin Extraction (HIE) index was also calculated.
RESULTS
ALA administration significantly improved insulin sensitivity and decreased ALT and AST plasma levels in all subjects, though no changes were observed on reproductive hormones. When PCOS patients were subdivided according to the presence or absence of familial diabetes background, the higher effects of ALA were observed in the former group that showed AST and ALT reduction and greater HIE index decrease.
CONCLUSION
ALA administration improved insulin sensitivity in overweight/obese PCOS patients, especially in those with familial predisposition to diabetes. ALA administration improved both peripheral sensitivity to insulin and liver clearance of insulin. Such effects potentially decrease the risk of nonalcoholic fat liver disease and diabetes in PCOS patients.
Topics: Female; Humans; Diabetes Mellitus; Insulin; Insulin Resistance; Non-alcoholic Fatty Liver Disease; Obesity; Overweight; Polycystic Ovary Syndrome; Retrospective Studies; Thioctic Acid
PubMed: 38622970
DOI: 10.1080/09513590.2024.2341701 -
Stem Cell Research & Therapy Apr 2024Erythroid and myeloid differentiation disorders are commonly occurred in leukemia. Given that the relationship between erythroid and myeloid lineages is still unclear....
BACKGROUND
Erythroid and myeloid differentiation disorders are commonly occurred in leukemia. Given that the relationship between erythroid and myeloid lineages is still unclear. To find the co-regulators in erythroid and myeloid differentiation might help to find new target for therapy of myeloid leukemia. In hematopoiesis, ALA (alpha lipoic acid) is reported to inhibit neutrophil lineage determination by targeting transcription factor ELK1 in granulocyte-monocyte progenitors via splicing factor SF3B1. However, further exploration is needed to determine whether ELK1 is a common regulatory factor for erythroid and myeloid differentiation.
METHODS
In vitro culture of isolated CD34, CMPs (common myeloid progenitors) and CD34 CD371 HSPCs (hematopoietic stem progenitor cells) were performed to assay the differentiation potential of monocytes, neutrophils, and erythrocytes. Overexpression lentivirus of long isoform (L-ELK1) or the short isoform (S-ELK1) of ELK1 transduced CD34 HSPCs were transplanted into NSG mice to assay the human lymphocyte and myeloid differentiation differences 3 months after transplantation. Knocking down of SRSF11, which was high expressed in CD371GMPs (granulocyte-monocyte progenitors), upregulated by ALA and binding to ELK1-RNA splicing site, was performed to analyze the function in erythroid differentiation derived from CD34 CD123 CD38 CD371 HPCs (hematopoietic progenitor cells). RNA sequencing of L-ELK1 and S-ELK1 overexpressed CD34 CD123 CD38 CD371 HPCs were performed to assay the signals changed by ELK1.
RESULTS
Here, we presented new evidence that ALA promoted erythroid differentiation by targeting the transcription factor ELK1 in CD34 CD371 hematopoietic stem progenitor cells (HSPCs). Overexpression of either the long isoform (L-ELK1) or the short isoform (S-ELK1) of ELK1 inhibited erythroid-cell differentiation, but knockdown of ELK1 did not affect erythroid-cell differentiation. RNAseq analysis of CD34 CD123 CD38 CD371 HPCs showed that L-ELK1 upregulated the expression of genes related to neutrophil activity, phosphorylation, and hypoxia signals, while S-ELK1 mainly regulated hypoxia-related signals. However, most of the genes that were upregulated by L-ELK1 were only moderately upregulated by S-ELK1, which might be due to a lack of serum response factor interaction and regulation domains in S-ELK1 compared to L-ELK1. In summary, the differentiation of neutrophils and erythrocytes might need to rely on the dose of L-ELK1 and S-ELK1 to achieve precise regulation via RNA splicing signals at early lineage commitment.
CONCLUSIONS
ALA and ELK1 are found to regulate both human granulopoiesis and erythropoiesis via RNA spliceosome, and ALA-ELK1 signal might be the target of human leukemia therapy.
Topics: Humans; Mice; Animals; Erythropoiesis; Thioctic Acid; Neutrophils; Interleukin-3 Receptor alpha Subunit; ets-Domain Protein Elk-1; Antigens, CD34; Cell Differentiation; Erythrocytes; Leukemia; Hypoxia; Protein Isoforms
PubMed: 38589882
DOI: 10.1186/s13287-024-03711-6 -
Poultry Science May 2024Inhibiting oxidative stress is key for ensuring sperm motility during semen cryopreservation. The aim of this study was to investigate the effect of adding alpha-lipoic...
Inhibiting oxidative stress is key for ensuring sperm motility during semen cryopreservation. The aim of this study was to investigate the effect of adding alpha-lipoic acid (ALA) as an extender in rooster semen cryopreservation. Different concentrations of ALA were added to the frozen diluent of rooster semen; subsequently, computer-aided semen analysis was used to determine membrane functional integrity, acrosome integrity, antioxidant capacity (based on T-AOC, GSH-Px, SOD, CAT, and MDA contents), and mitochondrial integrity. The frozen sperm ultrastructure was observed using transmission electron microscopy. The results showed that the addition of different concentrations of ALA partially to greatly improved the quality of frozen sperm; in particular, 8 μg/mL ALA significantly improved multiple parameters of sperm quality, including sperm motility and antioxidant enzyme activity, after freeze-thaw. The results of this study provide empirical and theoretical support for effective rooster semen cryopreservation and can inform the development of new protective agents in the field of livestock reproduction.
Topics: Animals; Cryopreservation; Semen Preservation; Male; Thioctic Acid; Oxidative Stress; Chickens; Antioxidants; Semen Analysis; Cryoprotective Agents; Semen; Spermatozoa; Sperm Motility
PubMed: 38518670
DOI: 10.1016/j.psj.2024.103632 -
[Correlation of serum ferredoxin 1 and lipoic acid levels with severity of coronary artery disease].Nan Fang Yi Ke Da Xue Xue Bao = Journal... Feb 2024To analyze the correlation of copper death inducer ferredoxin 1 (FDX1) and lipoic acid (LA) with the occurrence and severity of coronary atherosclerosis and explore...
OBJECTIVE
To analyze the correlation of copper death inducer ferredoxin 1 (FDX1) and lipoic acid (LA) with the occurrence and severity of coronary atherosclerosis and explore their roles in coronary heart disease (CHD).
METHODS
We analyzed the data of 226 patients undergoing coronary artery angiography (CAG) in our hospital between October, 2021 and October, 2022, including 47 patients with normal CAG findings (control group) and 179 patients with mild, moderate or severe coronary artery stenosis (CHD group). Serum FDX1 and LA levels were determined with ELISA for all the patients. We also examined pathological changes in the aorta of normal and ApoE mice using HE staining and observed collagen fiber deposition with Sirius red staining. Immunohistochemistry was used to detect the expression and distribution of FDX1 and LA in the aorta, and RT-PCR was performed to detect the expressions of FDX1, LIAS and ACO2 mRNAs in the myocardial tissues.
RESULTS
Compared with the control patients, CHD patients had significantly lower serum FDX1 and LA levels, which decreased progressively as coronary artery stenosis worsened ( < 0.01) and as the number of involved coronary artery branches increased ( < 0.05). Serum FDX1 and LA levels were positively correlated (=0.451, < 0.01) and they both negatively correlated with the Gensini score (=-0.241 and -0.273, respectively; < 0.01). Compared with normal mice, ApoE mice showed significantly increased lipid levels ( < 0.01) and atherosclerosis index, obvious thickening, lipid aggregation, and collagen fiber hyperplasia in the aorta, and significantly reduced expressions of FDX1, LA, LIAS, and ACO2 ( < 0.05).
CONCLUSION
Serum FDX1 and LA levels decrease with worsening of coronary artery lesions, and theirs expressions are correlated with coronary artery lesions induced by hyperlipidemia.
Topics: Humans; Animals; Mice; Coronary Artery Disease; Ferredoxins; Thioctic Acid; Coronary Stenosis; Apolipoproteins E; Collagen
PubMed: 38501416
DOI: 10.12122/j.issn.1673-4254.2024.02.13 -
Experimental Gerontology May 2024This study aimed to investigate the effects of combined alpha-lipoic acid (ALA) and mitoquinone (Mito Q) supplementation on cardiac function and the underlying...
BACKGROUND
This study aimed to investigate the effects of combined alpha-lipoic acid (ALA) and mitoquinone (Mito Q) supplementation on cardiac function and the underlying mechanisms in aged rats with myocardial infarction (MI).
METHODS
The aged rats underwent left anterior descending artery (LADA) occlusion for 30 min, followed by reperfusion for 24 h. ALA (100 mg/kg, gavage) and Mito Q (10 mg/kg, IP) were administered daily for two weeks before ischemia. Cardiac function, inflammatory, and apoptotic markers were evaluated 24 h after ischemia.
RESULTS
The results of this study indicated that the administration of the combination of ALA and Mito Q significantly improved cardiac function. This improvement was linked to a reduction in the expression of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β (P < 0.001) and apoptotic markers (Bax, caspase-3, and Cyt-c), as well as a decrease in the percentage of TUNEL-positive cells (P < 0.001).
CONCLUSION
The study revealed that combined intervention synergistically mitigated cardiac dysfunction by suppressing inflammatory and apoptotic pathways in aged rats with MI. Further research is needed to validate the potential of ALA and Mito Q as therapeutic options for elderly people at risk of heart attacks.
Topics: Humans; Aged; Rats; Animals; Thioctic Acid; Rats, Sprague-Dawley; Myocardial Infarction; Dietary Supplements; Apoptosis; Organophosphorus Compounds; Ubiquinone
PubMed: 38484905
DOI: 10.1016/j.exger.2024.112402 -
International Journal of Molecular... Feb 2024The prevalence and incidence of obesity and the comorbidities linked to it are increasing worldwide. Current therapies for obesity and associated pathologies have proven... (Review)
Review
The prevalence and incidence of obesity and the comorbidities linked to it are increasing worldwide. Current therapies for obesity and associated pathologies have proven to cause a broad number of adverse effects, and often, they are overpriced or not affordable for all patients. Among the alternatives currently available, natural bioactive compounds stand out. These are frequently contained in pharmaceutical presentations, nutraceutical products, supplements, or functional foods. The clinical evidence for these molecules is increasingly solid, among which epigallocatechin-3-gallate, ellagic acid, resveratrol, berberine, anthocyanins, probiotics, carotenoids, curcumin, silymarin, hydroxy citric acid, and α-lipoic acid stand out. The molecular mechanisms and signaling pathways of these molecules have been shown to interact with the endocrine, nervous, and gastroenteric systems. They can regulate the expression of multiple genes and proteins involved in starvation-satiety processes, activate the brown adipose tissue, decrease lipogenesis and inflammation, increase lipolysis, and improve insulin sensitivity. This review provides a comprehensive view of nature-based therapeutic options to address the increasing prevalence of obesity. It offers a valuable perspective for future research and subsequent clinical practice, addressing everything from the molecular, genetic, and physiological bases to the clinical study of bioactive compounds.
Topics: Humans; Anthocyanins; Obesity; Dietary Supplements; Resveratrol; Thioctic Acid
PubMed: 38473918
DOI: 10.3390/ijms25052671 -
International Journal of Molecular... Feb 2024Peripheral neuropathy is caused by a malfunction in the axons and myelin sheaths of peripheral nerves and motor and sensory neurons. In this context, nonpharmacological...
BACKGROUND
Peripheral neuropathy is caused by a malfunction in the axons and myelin sheaths of peripheral nerves and motor and sensory neurons. In this context, nonpharmacological treatments with antioxidant potential have attracted much attention due to the issues that some conventional pharmaceutical therapy can generate. Most of these treatments contain lipoic acid, but issues have emerged regarding its use. Considering this, the present study evaluated the beneficial effects of nutraceuticals based on dry extract 10:1 or lipoic acid in combination with other substances (such as citicholine, B vitamins, and acetyl L-carnitine).
METHOD
To assess the combination's absorption and biodistribution and exclude cytotoxicity, its bioavailability was first examined in a 3D intestinal barrier model that replicated oral ingestion. Subsequently, a 3D model of nerve tissue was constructed to investigate the impacts of the new combination on the significant pathways dysregulated in peripheral neuropathy.
RESULTS
Our findings show that the novel combination outperformed in initial pain relief response and in recovering the mechanism of nerve healing following Schwann cell injury by successfully crossing the gut barrier and reaching the target site.
CONCLUSION
This article describes a potential alternative nutraceutical approach supporting the effectiveness of combinations with extract in decreasing neuropathy and regulating pain pathways.
Topics: Humans; Thioctic Acid; Tissue Distribution; Neuralgia; Dietary Supplements; Drugs, Chinese Herbal
PubMed: 38397054
DOI: 10.3390/ijms25042376