synthesis, analysis and effects in diet-induced obese mice
Madawala, Samanthi R. P.
(2013).
Novel lipid derivatives for health benefits.
Diss. (sammanfattning/summary)
Uppsala :
Sveriges lantbruksuniv.,
Acta Universitatis Agriculturae Sueciae, 1652-6880
; 2013:62
ISBN 978-91-576-7862-1
eISBN 978-91-576-7863-8
[Doctoral thesis]
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Abstract
Obesity is a public health concern and requires effective management with multiple approaches. Dietary supplements of bioactive compounds that can improve fatty acid oxidation and thermogenesis are currently in focus to develop anti-obese food ingredients/nutraceuticals without side-effects. Dietary 1,3-diacylglycerol (DAG) and supplementation of α-lipoic acid (LA) have been shown to reduce fat accumulation and improve lipid profile while phytosterols (PS) are known for reducing blood cholesterol.
In this thesis, novel lipid derivatives of LA with PS and 1,3-DAG were synthesized based on the hypothesis, that they would possess advantages over the individual constituents in controlling obesity due to increased stability, solubility, and bioavailability. A mild esterification method was developed to synthesize conjugates of LA and its reduced form (DHLA), with PS and 1,3-DAG yielding 60-80% of the products. The novel DHLA derivatives showed higher in vitro free radical scavenging capacity than the corresponding LA derivatives, and were comparable to pure DHLA.
In a pilot in vitro study, LA derivative with 1,3-dilaurin (diLaLA) was completely hydrolyzed by pancreatic lipase, releasing monolipoate, C12:0 and LA. Free LA was detected in plasma 2 h after oral administration of diLaLA to mice. Effects of diLaLA on body weight and lipid metabolism were evaluated in male C57BL/6J diet-induced obese mice on a high fat diet (HFD) and a control treated only with vehicle. After oral administration of diLaLA at 10, 50 and 250 mg/kg body wt. daily for 6 weeks, body weight was lowered (p<0.05) in high dose group compared with the control and low dose groups. Treatment with high dose also reduced (p<0.05) plasma and hepatic free fatty acid contents, while the concentrations of blood glucose, total cholesterol, and liver triacylglycerol showed a reducing trend compared with the control. Stearoyl-CoA desaturase (SCD)-1 activity, estimated by SCD16 index (C16:1n-7/C16:0), showed lower activity (p<0.05) in white adipose tissues while some key genes involved in fatty acid β-oxidation in liver showed upregulation in the high dose group compared with the control. Oral treatment with diLaLA reduced HFD-induced obesity in mice, possibly through enhanced energy expenditure via β-oxidation and suppressing in vivo lipogenesis, suggesting its potential as a promising candidate against obesity.
Authors/Creators: | Madawala, Samanthi R. P. | ||||||||||||
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Title: | Novel lipid derivatives for health benefits | ||||||||||||
Subtitle: | synthesis, analysis and effects in diet-induced obese mice | ||||||||||||
Series/Journal: | Acta Universitatis Agriculturae Sueciae (1652-6880) | ||||||||||||
Year of publishing : | 2013 | ||||||||||||
Number: | 2013:62 | ||||||||||||
Number of Pages: | 75 | ||||||||||||
Papers/manuscripts: |
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Place of Publication: | Uppsala | ||||||||||||
Publisher: | Dept. of Food Science, Swedish University of Agricultural Sciences | ||||||||||||
ISBN for printed version: | 978-91-576-7862-1 | ||||||||||||
ISBN for electronic version: | 978-91-576-7863-8 | ||||||||||||
ISSN: | 1652-6880 | ||||||||||||
Language: | English | ||||||||||||
Publication Type: | Doctoral thesis | ||||||||||||
Full Text Status: | Public | ||||||||||||
Agris subject categories.: | Q Food science > Q01 Food science and technology S Human nutrition > S30 Diet and diet-related diseases | ||||||||||||
Subjects: | (A) Swedish standard research categories 2011 > 4 Agricultural Sciences > 401 Agricultural, Forestry and Fisheries > Food Science | ||||||||||||
Agrovoc terms: | lipoic acid, lipid metabolism, overweight, weight reduction, weight reduction diet, phytosterols, lauric acid, biosynthesis, mice, laboratory animals | ||||||||||||
Keywords: | Novel lipid derivatives, Body weight reduction, Lipid metabolism, Phytosterol derivatives, Lipoic acid, Diacylglycerol | ||||||||||||
URN:NBN: | urn:nbn:se:slu:epsilon-e-1659 | ||||||||||||
Permanent URL: | http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-e-1659 | ||||||||||||
ID Code: | 10844 | ||||||||||||
Department: | (NL, NJ) > Dept. of Food Science (until 161231) | ||||||||||||
Deposited By: | Samanthi R. P. Madawala | ||||||||||||
Deposited On: | 10 Oct 2013 06:18 | ||||||||||||
Metadata Last Modified: | 14 Dec 2014 08:56 |
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