scholarly journals Lipolytic and Hypolipidemic Properties of Newly Synthesized Aryloxypropanolamine Derivatives

2008 ◽  
Vol 77 (4) ◽  
pp. 589-594
Author(s):  
J. Krčmář ◽  
H. Kotolová ◽  
M. Karpíšek ◽  
L. Veselá ◽  
P. Kollár ◽  
...  

In this study, the lipolytic effect of two newly synthesized potential β3-adrenergic agonists A482 and B496 in active acid forms was tested using isolated sliced epididymal adipose tissue of Wistar rats, and compared with Isoprenaline and BRL37344. Furthermore, effects of an eight-week oral administration of the newly synthesized substances on serum cholesterol, triglycerides, glucose, adiponectin, resistin and weight gain were studied in C57Bl/6J mice that were fed high energy diet. The newly synthesized substance A482 (4-(2-{[2-hydroxy-3-(4-methyl-carbamoylphenoxy) propyl]amino}ethyl)phenoxy-acetic acid hydrochloride) was able to produce almost full lipolysis at a 1 × 10-7 M concentration, and its effect on the rat epididymal adipose tissue was similar to the specific β3-adrenergic agonist BRL37344. Ethyl ester of this substance significantly lowered plasma total cholesterol (p < 0.001), resistin (p < 0.01), weight gain (p < 0.01), improved total/HDL-cholesterol ratio (p < 0.01) and increased circulating adiponectin (p < 0.001) in C57Bl/6J mice that were fed high energy diet. The second tested substance B496 did not show all activities expected from β3-adrenergic agonists. Our results suggest that the newly synthesised substance A482 may represent a potent β3-adrenergic agonist.

2017 ◽  
Vol 61 (1) ◽  
pp. 1347480 ◽  
Author(s):  
Li-Han Chen ◽  
Yi-Wen Chien ◽  
Chung-Tiang Liang ◽  
Ching-Hung Chan ◽  
Meng-Han Fan ◽  
...  

1989 ◽  
Vol 256 (6) ◽  
pp. E740-E746
Author(s):  
R. H. Eckel ◽  
T. J. Yost

The effect of weight reduction on fasting serum lipids and lipoproteins and adipose tissue lipoprotein lipase responsiveness to insulin was assessed immediately after and 3 mo subsequent to a mean 11.7% weight reduction in 14 women. Whereas reduction in fasting serum triglycerides persisted after 3 mo, reductions in serum cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein (HDL) cholesterol were not found at 3 mo. In fact, at 3 mo, levels of HDL cholesterol were higher than before weight reduction. Maintenance of the reduced-obese state also increased the HDL2-to-HDL3 cholesterol ratio (P less than 0.01), an effect strongly associated with the change in the responsiveness of adipose tissue lipoprotein lipase to insulin (r = 0.821, P less than 0.001). Moreover, after maintenance of the reduced-obese state, the HDL2-to-HDL3 cholesterol ratio also increased after the ingestion of corn oil and a 6-h insulin-glucose infusion, a response not present before weight reduction. Thus the effect of weight reduction on serum lipids and lipoproteins was not only time dependent, but for HDL, was strongly associated with changes in adipose tissue metabolism.


2021 ◽  
Vol 49 (08) ◽  
pp. 1929-1948
Author(s):  
Yo-Han Han ◽  
Ji-Ye Kee ◽  
Seung-Heon Hong

Although gomisin A (GA) alleviates cancer and inflammation, its anti-obesity effect and the underlying mechanism have not yet been elucidated. Therefore, in this study, we aimed to elucidate the anti-obesity effects of GA by investigating the phenotypic changes involved in the browning and whitening of adipocytes. Here, obesity was induced to C57BL/6J mice using a high-fat diet (HFD). We administrated GA and checked weight changes for 12 weeks. We found that GA decreased the weight of weight gain, epididymal white adipose tissue (eWAT), and liver in the mice. In addition, the administration of GA elevated the levels of high-density lipoprotein (HDL)-cholesterol in the mice serum. Moreover, even after 12 weeks of treatment with GA, it did not cause any hepatic and renal toxicity. However, we found that GA induced the browning of eWAT and inhibited the whitening of brown adipose tissue. We further confirmed the anti-obesity mechanism of GA using 3T3-L1 cells, the human adipose mesenchymal stem cells (hAMSCs), and primary brown adipocytes (BAs) in vitroexperiments. We found that GA suppressed adipogenesis via the activation of AMP-activated protein kinase (AMPK). Furthermore, GA-induced browning by increasing the expression levels of uncoupling protein 1 (UCP1) in hAMSCs. The results of our study indicate that GA can inhibit weight gain by regulating the phenotypic changes involved in the browning and whitening of adipose tissues, which makes it a potential therapeutic agent for the treatment of obesity.


2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Zongji Zheng ◽  
Xiaomeng Liu ◽  
Qianwei Zhao ◽  
Lei Zhang ◽  
Chenzhong Li ◽  
...  

Background.White adipose tissue browning may be a promising strategy to combat obesity. UCP1 is strongly induced in White adipose tissue withβ3-adrenergic agonist treatment, but the causes of this increase have not been fully elucidated. This study aims to explore more miRNAs involved in the process of browning of visceral adipose tissue.Methods.Total of fourteen mice were randomly divided into control and study group. Study group mice were injected intraperitoneally with CL316243 once daily for seven days; meanwhile the control group were treated with 0.9% NaCl. After a 7-day period, the expression of genes involved in WAT browning and potential UCP1-targeting miRNAs in adipose tissues was analyzed by qPCR.Results.qPCR analysis revealed that UCP1, DIO2, CIDEA, and CPT1B in epididymal adipose tissue were overexpressed in CL316243 group. Furthermore, potential UCP1-targeting miR-9 and miR-338-3p in epididymal adipose tissue were significantly decreased in CL316243 group.Conclusion.This suggests that potential UCP1-targeting miR-9 and miR-338-3p may be involved in the browning of epididymal adipose tissue by regulating UCP1 gene expression. In this study, we demonstrated that this increase of UCP1 is due, at least in part, to the decreased expression of certain UCP1-targeting miRNAs in epididymal adipose tissue compared to control.


Nutrients ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 604 ◽  
Author(s):  
Jung Eun Park ◽  
Suk-Heung Oh ◽  
Youn-Soo Cha

Our previous study reported that lactic acid bacteria (L. brevis OPK-3) isolated from kimchi ameliorated intracellular lipid accumulation in 3T3-L1 adipocyte. The current study explored potential roles of L. brevis OPK-3 (KLAB) on preventing body weight gain and its effect on the inflammatory response of adipose tissue. Male C57BL/6 mice (n = 10) were divided into four groups: normal diet with distilled water (NDC), high-fat diet with distilled water (HDC), high-fat diet with L-ornithine (OTC) or high-fat diet with KLAB. The KLAB supplement resulted in significantly lower body weight, lower epididymal fat tissue mass, and lower serum and hepatic TG levels than the HDC. KLAB supplementation improved serum cytokines, and real-time polymerase chain reaction (PCR) analysis showed significantly lower inflammatory cytokine mRNA levels in epididymal adipose tissue. These results suggest that the administration of KLAB inhibits the induction of inflammation in adipose tissue along with the inhibition of weight gain. Therefore, this study demonstrates the therapeutic and beneficial value of this strain produced during the fermentation of kimchi.


Nutrients ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1509 ◽  
Author(s):  
Sandramara Sasso ◽  
Priscilla Cristovam Sampaio e Souza ◽  
Lidiani Figueiredo Santana ◽  
Claudia Andréa Lima Cardoso ◽  
Flávio Macedo Alves ◽  
...  

Annona muricata Linn, commonly known as graviola, is one of the most popular plants used in Brazil for weight loss. The aim of this study is to evaluate the therapeutic effects of three different doses (50 mg/kg, 100 mg/kg, and 150 mg/kg) of aqueous graviola leaf extract (AGE) supplemented by oral gavage, on obese C57BL/6 mice. Food intake, body weight, an oral glucose tolerance test (OGTT), an insulin sensitivity test, quantification of adipose tissue cytokines, weight of fat pads, and serum biochemical and histological analyses of the liver, pancreas, and epididymal adipose tissue were measured. AGE had an anti-inflammatory effect by increasing IL-10 at doses of 50 and 100 mg/kg. Regarding the cholesterol profile, there was a significant decrease in LDL-cholesterol levels in the AGE 150 group, and VLDL-cholesterol and triglycerides in the AGE 100 and 150 groups. There was an increase in HDL cholesterol in the AGE 150 group. The extract was able to reduce the adipocyte area of the epididymal adipose tissue in the AGE 100 and 150 groups. According to the histological analysis of the liver and pancreas, no significant difference was found among the groups. There were no significant effects of AGE on OGTT and serum fasting glucose concentration. However, the extract was effective in improving glucose tolerance in the AGE 150 group.


2011 ◽  
Vol 108 (4) ◽  
pp. 581-587 ◽  
Author(s):  
Bolin Qin ◽  
Richard A. Anderson

Chokeberries are a rich source of anthocyanins, which may contribute to the prevention of obesity and the metabolic syndrome. The aim of the present study was to determine if an extract from chokeberries would reduce weight gain in rats fed a fructose-rich diet (FRD) and to explore the potential mechanisms related to insulin signalling, adipogenesis and inflammatory-related pathways. Wistar rats were fed a FRD for 6 weeks to induce insulin resistance, with or without chokeberry extract (CBE) added to the drinking-water (100 and 200 mg/kg body weight, daily: CBE100 and CBE200). Both doses of CBE consumption lowered epididymal fat, blood glucose, TAG, cholesterol and LDL-cholesterol. CBE consumption also elevated plasma adiponectin levels and inhibited plasma TNF-α and IL6, compared with the control group. There were increases in the mRNA expression for Irs1, Irs2, Pi3k, Glut1, Glut4 and Gys1, and decreases in mRNA levels of Gsk3β. The protein and gene expression of adiponectin and Pparγ mRNA levels were up-regulated and Fabp4, Fas and Lpl mRNA levels were inhibited. The levels of gene expression of inflammatory cytokines, such as Il1β, Il6 and Tnfα were lowered, and protein and gene expression of ZFP36 (zinc finger protein) were enhanced in the epididymal adipose tissue of the rats that consumed the CBE200 extract. In summary, these results suggest that the CBE decreased risk factors related to insulin resistance by modulating multiple pathways associated with insulin signalling, adipogenesis and inflammation.


2015 ◽  
Vol 225 (3) ◽  
pp. 191-204 ◽  
Author(s):  
Barbara C Fam ◽  
Rebecca Sgambellone ◽  
Zheng Ruan ◽  
Joseph Proietto ◽  
Sofianos Andrikopoulos

Obesity susceptibility in humans and in rodent strains varies in response to the consumption of high-energy density (HED) diets. However, the exact mechanism(s) involved in this susceptibility remain(s) unresolved. The aim of the present study was to gain greater insight into this susceptibility by using C57BL/6J (B6) mice that were separated into obesity-prone (diet-induced obese (DIO)) and obesity-resistant (diet-induced resistant (DR)) groups following an HED diet for 6 weeks. Physiological, biochemical and gene expression assessments of energy balance were performed in the DIO and DR mice on an HED diet and chow-fed mice. The increased weight gain of the DIO mice as compared to the DR mice was associated with increased energy intake and higher plasma leptin and adiponectin levels but not with reduced physical activity or resting energy expenditure. HypothalamicPomcgene expression was elevated, but there were no changes inNpyorAgrpexpression. Adipose tissue leptin and adiponectin gene expression were significantly reduced in the DIO group as compared to the DR group. Interestingly, ileum expression of G protein-coupled receptor (Gpr) 40 (Gpr40) was significantly increased, whereasGpr120,Gpr119,Gpr41, and glucagon-like peptide 1 (Glp1) were reduced. Contrastingly, the lower weight gain of the DR group was associated with elevated adipose tissue leptin and adiponectin gene expression, but there were no differences in plasma hormone or hypothalamic gene expression levels as compared to chow-fed mice. Therefore, the present data demonstrate that susceptibility and resistance to diet-induced weight gain in B6 mice appears to be predominantly driven by peripheral rather than hypothalamic modifications, and changes in gut-specific receptors are a potentially important contributor to this variation.


2018 ◽  
Vol 3 ◽  
pp. 151-160 ◽  
Author(s):  
Alexander Gosslau ◽  
Emmanuel Zachariah ◽  
Shiming Li ◽  
Chi-Tang Ho

Effects of a theaflavin-enriched black tea extract (BTE) against type 2 diabetes (T2D) were analyzed using the obese ZDF model. ZDF rats were hyperglycemic, dyslipidemic and express pro-inflammatory markers. BTE was well tolerated and caused an elevation of fasted and fed glucose as well as lower glucose tolerance in contrast to hypoglycemic effects by metformin. However, the BTE group showed decreased levels of LDL and triacylglycerols which corresponded to an increase in free fatty acids. Positive effects against dyslipidemia of BTE corresponded to a significant decrease in weight gain. The impact on inflammatory pathways was analyzed by expression analysis of inflammatory mediators in whole blood and epididymal adipose tissue using TaqMan PCR and ELISA. Whole blood analysis revealed a significant down-regulation of ICAM-1 and TNF-α, whereas IL-4, IL-6, IL-10, IL-13 and IFN-γ were elevated to higher levels as compared to ibuprofen. In adipose tissue, BTE treatment induced an upregulation of COX-2 and IL-6. Thus, BTE treatment showed strong effects against systemic inflammation and caused a reduction of weight gain with positive effects against dyslipidemia. The complexity of signaling pathways leading to complications in diabetes suggest a treatment of BTE in combination with antidiabetic therapeutics as promising strategy against T2D.


Author(s):  
M. I. Dmitrievskaya ◽  
S. E. Balitskiy ◽  
A. G. Balandina ◽  
I. S. Glazkov

Obesity is the most widespread chronic disease today; it occurs when the process of consumption exceeds energy expenditure processes. Since adequate drug treatment for obesity at the moment isn’t found, research and introduction of new substances that activate β3-AR, is a promising pharmacological objective. One such drug became mirabegron known as a drug for the treatment of OAB. It’s stimulating effect on the brown and beige adipose tissue contribute to enhancing fatty acid oxidation and the release of energy, with a decrease in fat mass. However, because of side effects on the cardiovascular system, and a long course of therapy to a clinically significant result, mirabegron is not currently used as a remedy for obesity, but others β3-adrenergic agonists will be designed in the future and they will smooth disadvantages of mirabegron.


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