scholarly journals Antiadipogenesis of Oroxylum indicum (L.) Kurz Extract via PPARγ2 in 3T3-L1 Adipocytes

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Tanaporn Hengpratom ◽  
Apichart Ngernsoungnern ◽  
Piyada Ngernsoungnern ◽  
Gordon Matthew Lowe ◽  
Griangsak Eumkeb
Keyword(s):  
Glucose Transporter ◽  
Regulatory Element ◽  
Fatty Acid Synthetase ◽  
Enzyme Linked Immunosorbent Assay ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Oroxylum Indicum ◽  
Intracellular Lipid Accumulation ◽  
Glucose Transporter Glut4 ◽  
The Impact

Oroxylum indicum is regarded as a traditional food with medicinal properties and is used widely throughout Asia. It has previously been demonstrated that O. indicum extract (OIE) was able to suppress the differentiation of 3T3-L1 preadipocytes to adipocytes. However, the mechanism underlying the antiadipogenesis of this plant has not been fully investigated. The present study aimed to explore the impact of OIE at 50 to 200 μg mL−1 on the molecular mechanism involved in the antiadipogenic activity in 3T3-L1 cells at day 0 of their differentiation to adipocytes. The morphology and biochemistry of the cells on day 12 were investigated and compared to the relevant controls. Adiponectin was measured using enzyme-linked immunosorbent assay (ELISA). The mRNA expression of peroxisome proliferator-activated receptor-gamma 2 (PPARγ2), sterol regulatory element-binding proteins 1c (SREBP-1c), fatty acid synthetase (FAS), glucose transporter (GLUT4), and leptin in adipocytes was determined by real-time PCR. The results demonstrated that the OIE at 200 μg mL−1 exhibited strongest suppression on intracellular lipid accumulation. The levels of adiponectin were dramatically increased in the untreated adipocytes, whereas significantly decreased in the 200 μg mL−1 OIE-treated adipocytes (P<0.05). Expression of the mRNAs revealed that OIE-treated adipocytes at 200 μg mL−1 significantly inhibited the expression of PPARγ2 and SREBP-1c and lowered the level of expression of GLUT4, FAS, and leptin compared to the control (P<0.05). These findings suggest that OIE inhibits adipocyte differentiation along with the downregulation of PPARγ2, SREBP-1c, and GLUT4, leading to the decrease in the expression of FAS and adipokine (leptin and adiponectin). Thus, OIE might be developed for hyperlipidemia and obesity prevention.

scholarly journals A Review on the Medicinal and Pharmacological Properties of Traditional Ethnomedicinal Plant Sonapatha, Oroxylum indicum

Sinusitis ◽  
2021 ◽  
Vol 5 (1) ◽  
pp. 71-89
Author(s):  
Ganesh Chandra Jagetia
Keyword(s):  
Glucose Transporter ◽  
Skin Diseases ◽  
Regulatory Element ◽  
Experimental Studies ◽  
Fatty Acid Synthetase ◽  
Preclinical Models ◽  
Oroxylin A ◽  
Oroxylum Indicum

Oroxylum indicum, Sonapatha is traditionally used to treat asthma, biliousness, bronchitis, diarrhea, dysentery, fevers, vomiting, inflammation, leukoderma, skin diseases, rheumatoid arthritis, wound injury, and deworm intestine. This review has been written by collecting the relevant information from published material on various ethnomedicinal and pharmacological aspects of Sonapatha by making an internet, PubMed, SciFinder, Science direct, and Google Scholar search. Various experimental studies have shown that Sonapatha scavenges different free radicals and possesses alkaloids, flavonoids, cardio glycosides, tannins, sterols, phenols, saponins, and other phytochemicals. Numerous active principles including oroxylin A, chrysin, scutellarin, baicalein, and many more have been isolated from the different parts of Sonapatha. Sonapatha acts against microbial infection, cancer, hepatic, gastrointestinal, cardiac, and diabetic disorders. It is useful in the treatment of obesity and wound healing in in vitro and in vivo preclinical models. Sonapatha elevates glutathione, glutathione-s-transferase, glutathione peroxidase, catalase, and superoxide dismutase levels and reduces aspartate transaminase alanine aminotransaminase, alkaline phosphatase, lactate dehydrogenase, and lipid peroxidation levels in various tissues. Sonapatha activates the expression of p53, pRb, Fas, FasL, IL-12, and caspases and inhibited nuclear factor kappa (NF-κB), cyclooxygenase (COX-2), tumor necrosis factor (TNFα), interleukin (IL6), P38 activated mitogen-activated protein kinases (MAPK), fatty acid synthetase (FAS), sterol regulatory element-binding proteins 1c (SREBP-1c), proliferator-activated receptor γ2 (PPARγ2), glucose transporter (GLUT4), leptin, and HPV18 oncoproteins E6 and E7 at the molecular level, which may be responsible for its medicinal properties. The phytoconstituents of Sonapatha including oroxylin A, chrysin, and baicalein inhibit the replication of SARS-CoV-2 (COVID-19) in in vitro and in vivo experimental models, indicating its potential to contain COVID-19 infection in humans. The experimental studies in various preclinical models validate the use of Sonapatha in ethnomedicine and Ayurveda.

scholarly journals The Impact of Anthocyanins and Iridoids on Transcription Factors Crucial for Lipid and Cholesterol Homeostasis

2021 ◽  
Vol 22 (11) ◽  
pp. 6074
Author(s):  
Maciej Danielewski ◽  
Agnieszka Matuszewska ◽  
Adam Szeląg ◽  
Tomasz Sozański
Keyword(s):  
Transcription Factors ◽  
Cholesterol Metabolism ◽  
Binding Protein ◽  
Regulatory Element ◽  
Cholesterol Homeostasis ◽  
Lipid Lowering ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Cell Functions ◽  
The Impact

Nutrition determines our health, both directly and indirectly. Consumed foods affect the functioning of individual organs as well as entire systems, e.g., the cardiovascular system. There are many different diets, but universal guidelines for proper nutrition are provided in the WHO healthy eating pyramid. According to the latest version, plant products should form the basis of our diet. Many groups of plant compounds with a beneficial effect on human health have been described. Such groups include anthocyanins and iridoids, for which it has been proven that their consumption may lead to, inter alia, antioxidant, cholesterol and lipid-lowering, anti-obesity and anti-diabetic effects. Transcription factors directly affect a number of parameters of cell functions and cellular metabolism. In the context of lipid and cholesterol metabolism, five particularly important transcription factors can be distinguished: liver X receptor (LXR), peroxisome proliferator-activated receptor-α (PPAR-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), CCAAT/enhancer binding protein α (C/EBPα) and sterol regulatory element-binding protein 1c (SREBP-1c). Both anthocyanins and iridoids may alter the expression of these transcription factors. The aim of this review is to collect and systematize knowledge about the impact of anthocyanins and iridoids on transcription factors crucial for lipid and cholesterol homeostasis.

scholarly journals SREBP-1c/MicroRNA 33b Genomic Loci Control Adipocyte Differentiation

2016 ◽  
Vol 36 (7) ◽  
pp. 1180-1193 ◽  
Author(s):  
Nathan L. Price ◽  
Brandon Holtrup ◽  
Stephanie L. Kwei ◽  
Martin Wabitsch ◽  
Matthew Rodeheffer ◽  
...  
Keyword(s):  
Lipid Droplet ◽  
Target Genes ◽  
Adipocyte Differentiation ◽  
Regulatory Element ◽  
Critical Role ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
The Impact

White adipose tissue (WAT) is essential for maintaining metabolic function, especially during obesity. The intronic microRNAs miR-33a and miR-33b, located within the genes encoding sterol regulatory element-binding protein 2 (SREBP-2) and SREBP-1, respectively, are transcribed in concert with their host genes and function alongside them to regulate cholesterol, fatty acid, and glucose metabolism. SREBP-1 is highly expressed in mature WAT and plays a critical role in promotingin vitroadipocyte differentiation. It is unknown whether miR-33b is induced during or involved in adipogenesis. This is in part due to loss of miR-33b in rodents, precludingin vivoassessment of the impact of miR-33b using standard mouse models. This work demonstrates that miR-33b is highly induced upon differentiation of human preadipocytes, along withSREBP-1. We further report that miR-33b is an important regulator of adipogenesis, as inhibition of miR-33b enhanced lipid droplet accumulation. Conversely, overexpression of miR-33b impaired preadipocyte proliferation and reduced lipid droplet formation and the induction of peroxisome proliferator-activated receptor γ (PPARγ) target genes during differentiation. These effects may be mediated by targeting of HMGA2, cyclin-dependent kinase 6 (CDK6), and other predicted miR-33b targets. Together, these findings demonstrate a novel role of miR-33b in the regulation of adipocyte differentiation, with important implications for the development of obesity and metabolic disease.

scholarly journals Abdominal Fat SIRT6 Expression and Its Relationship with Inflammatory and Metabolic Pathways in Pre-Diabetic Overweight Patients

2019 ◽  
Vol 20 (5) ◽  
pp. 1153 ◽  
Author(s):  
Nunzia D’Onofrio ◽  
Gorizio Pieretti ◽  
Feliciano Ciccarelli ◽  
Antonio Gambardella ◽  
Nicola Passariello ◽  
...  
Keyword(s):  
Regulatory Element ◽  
Abdominal Fat ◽  
Control Group ◽  
Diabetic Patients ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Metformin Therapy ◽  
Ppar Γ ◽  
Visceral Abdominal Fat ◽  
Factor Α

: The role of sirtuin 6 (SIRT6) in adipose abdominal tissue of pre-diabetic (pre-DM) patients is poorly known. Here, we evaluated SIRT6 expression in visceral abdominal fat of obese pre-diabetic patients and the potential effects of metformin therapy. Results indicated that obese pre-DM subjects showed low SIRT6 protein expression and high expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), peroxisome proliferator-activated receptor gamma (PPAR-γ), and sterol regulatory element-binding transcription factor 1 (SREBP-1). Obese pre-DM patients showed high values of glucose, insulin resistance (HOMA-IR), C reactive protein (CRP), nitrotyrosine, tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6), and low values of insulin (p < 0.05). Of note, abdominal fat tissue of obese pre-DM patients treated with metformin therapy presented higher SIRT6 expression and lower NF-κB, PPAR-γ, and SREBP-1 expression levels compared to pre-DM control group. Collectively, results show that SIRT6 is involved in the inflammatory pathway of subcutaneous abdominal fat of obese pre-DM patients and its expression responds to metformin therapy.

scholarly journals Zidovudine Impairs Adipogenic Differentiation through Inhibition of Clonal Expansion

2008 ◽  
Vol 52 (8) ◽  
pp. 2882-2889 ◽  
Author(s):  
Metodi V. Stankov ◽  
Reinhold E. Schmidt ◽  
Georg M. N. Behrens
Keyword(s):  
Adipogenic Differentiation ◽  
Clonal Expansion ◽  
Inhibitory Effect ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Triglyceride Accumulation ◽  
Thymidine Incorporation Assay ◽  
Human Preadipocytes ◽  
Incorporation Assay ◽  
The Impact

ABSTRACT Lipoatrophy is a prevalent side effect of treatment with thymidine analogues. We wished to confine the time point of the antiadipogenic effect of zidovudine (AZT) during adipogenesis and to evaluate the antiproliferative effect of AZT on adipocyte homeostasis. We investigated the effects of AZT on adipogenesis in 3T3-F442A cells and studied their proliferation, differentiation, viability, and adiponectin expression. Cells were exposed to AZT (1 μM, 3 μM, 6 μM, and 180 μM), stavudine (d4T; 3 μM), or dideoxycytosine (ddC; 0.1 μM) for up to 15 days. Differentiation was assessed by real-time PCR and quantification of triglyceride accumulation. Proliferation and clonal expansion were determined by a [3H]thymidine incorporation assay. When they were induced to differentiate in the presence of AZT at the maximum concentration in plasma (C max) and lower concentrations, 3T3-F442A preadipocytes failed to accumulate cytoplasmic triacylglycerol and failed to express normal levels of the later adipogenic transcription factors, CCAAT/enhancer-binding protein α and peroxisome proliferator-activated receptor γ. AZT exerted an inhibitory effect on the completion of the mitotic clonal expansion, which resulted in incomplete 3T3-F442A differentiation and, finally, a reduction in the level of adiponectin expression. In addition, AZT impaired the constitutive proliferation in murine and primary human subcutaneous preadipocytes. In contrast, incubation with d4T and ddC at the C max did not affect either preadipocyte proliferation or clonal expansion and differentiation. We conclude that the antiproliferative and antiadipogenetic effects of AZT on murine and primary human preadipocytes reveal the impact of the drug on fat tissue regeneration. These effects of the drug are expected to contribute to disturbed adipose tissue homeostasis and to be influenced by differential drug concentration and penetration in individual patients.

The effect of long term under- and over-feeding on the expression of genes related to lipid metabolism in mammary tissue of sheep

2014 ◽  
Vol 82 (1) ◽  
pp. 107-112 ◽  
Author(s):  
Eleni Tsiplakou ◽  
Emmanouil Flemetakis ◽  
Evangelia-Diamanto Kouri ◽  
Kyriaki Sotirakoglou ◽  
George Zervas
Keyword(s):  
Fatty Acid ◽  
Regulatory Element ◽  
Fatty Acid Synthetase ◽  
Hormone Sensitive Lipase ◽  
Mammary Tissue ◽  
Positive Energy ◽  
Peroxisome Proliferator ◽  
Nutritional Regulation ◽  
Expression Of Genes

Milk fatty acid (FA) synthesis by the mammary gland involves expression of a large number of genes whose nutritional regulation remains poorly defined. In this study, we examined the effect of long-term under- and over-feeding on the expression of genes (acetyl Co A carboxylase, ACC; fatty acid synthetase, FAS; lipoprotein lipase, LPL; stearoyl Co A desaturase, SCD; peroxisome proliferator activated receptor γ2, PPARγ2; sterol regulatory element binding protein-1, SREBP-1c; and hormone sensitive lipase, HSL) related to FA metabolism in sheep mammary tissue (MT). Twenty-four lactating sheep were divided into three homogenous sub-groups and fed the same ration in quantities covering 70% (underfeeding), 100% (control) and 130% (overfeeding) of their energy and crude protein requirements. The results showed a significant reduction of mRNA of ACC, FAS, LPL and SCD in the MT of underfed sheep, and a significant increase on the mRNA of LPL and SREBP-1c in the MT of overfed compared with the control respectively. In conclusion, the negative, compared to positive, energy balance in sheep down-regulates ACC, FAS, LPL, SCD, SREBP-1c and PPARγ2 expression in their MT which indicates that the decrease in nutrient availability may lead to lower rates of lipid synthesis.

A Tale of Two Diseases: Exploring Mechanisms Linking Diabetes Mellitus with Alzheimer’s Disease

2021 ◽  
pp. 1-17
Author(s):  
Jessica Lynn ◽  
Mingi Park ◽  
Christiana Ogunwale ◽  
George K. Acquaah-Mensah
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glycogen Synthase ◽  
Mammalian Target Of Rapamycin ◽  
Insulin Receptors ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Main Component ◽  
The Impact

Dementias, including the type associated with Alzheimer’s disease (AD), are on the rise worldwide. Similarly, type 2 diabetes mellitus (T2DM) is one of the most prevalent chronic diseases globally. Although mechanisms and treatments are well-established for T2DM, there remains much to be discovered. Recent research efforts have further investigated factors involved in the etiology of AD. Previously perceived to be unrelated diseases, commonalities between T2DM and AD have more recently been observed. As a result, AD has been labeled as “type 3 diabetes”. In this review, we detail the shared processes that contribute to these two diseases. Insulin resistance, the main component of the pathogenesis of T2DM, is also present in AD, causing impaired brain glucose metabolism, neurodegeneration, and cognitive impairment. Dysregulation of insulin receptors and components of the insulin signaling pathway, including protein kinase B, glycogen synthase kinase 3β, and mammalian target of rapamycin are reported in both diseases. T2DM and AD also show evidence of inflammation, oxidative stress, mitochondrial dysfunction, advanced glycation end products, and amyloid deposition. The impact that changes in neurovascular structure and genetics have on the development of these conditions is also being examined. With the discovery of factors contributing to AD, innovative treatment approaches are being explored. Investigators are evaluating the efficacy of various T2DM medications for possible use in AD, including but not limited to glucagon-like peptide-1 receptor agonists, and peroxisome proliferator-activated receptor-gamma agonists. Furthermore, there are 136 active trials involving 121 therapeutic agents targeting novel AD biomarkers. With these efforts, we are one step closer to alleviating the ravaging impact of AD on our communities.

Functional genomic characterization of delipidation elicited by trans-10, cis-12-conjugated linoleic acid (t10c12-CLA) in a polygenic obese line of mice

2005 ◽  
Vol 21 (3) ◽  
pp. 351-361 ◽  
Author(s):  
Ralph L. House ◽  
Joseph P. Cassady ◽  
Eugene J. Eisen ◽  
Thomas E. Eling ◽  
Jennifer B. Collins ◽  
...  
Keyword(s):  
Gene Expression ◽  
Linoleic Acid ◽  
Glucose Transporter ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Liver Weight ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Adult Mice ◽  
Brown Adipose

Gene expression was measured during t10c12-CLA-induced body fat reduction in a polygenic obese line of mice. Adult mice ( n = 185) were allotted to a 2 × 2 factorial experiment consisting of either nonobese (ICR-control) or obese (M16-selected) mice fed a 7% fat, purified diet containing either 1% linoleic acid (LA) or 1% t10c12-CLA. Body weight (BW) by day 14 was 12% lower in CLA- compared with LA-fed mice ( P < 0.0001). By day 14, t10c12-CLA reduced weights of epididymal, mesenteric, and brown adipose tissues, as a percentage of BW, in both lines by 30, 27, and 58%, respectively, and increased liver weight/BW by 34% ( P < 0.0001). Total RNA was isolated and pooled (4 pools per tissue per day) from epididymal adipose ( days 5 and 14) of the obese mice to analyze gene expression profiles using Agilent mouse oligo microarray slides representing >20,000 genes. Numbers of genes differentially expressed by greater than or equal to twofold in epididymal adipose ( days 5 and 14) were 29 and 125, respectively. It was concluded that, in adipose tissue, CLA increased expression of uncoupling proteins (1 and 2), carnitine palmitoyltransferase system, tumor necrosis factor-α ( P < 0.05), and caspase-3 but decreased expression of peroxisome proliferator-activated receptor-γ, glucose transporter-4, perilipin, caveolin-1, adiponectin, resistin, and Bcl-2 ( P < 0.01). In conclusion, this experiment has revealed candidate genes that will be useful in elucidating mechanisms of adipose delipidation.

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