Metabolic changes associated with the effect of Morinda citrifolia L. leaf extract in the prevention and treatment of obesity in Sprague- Dawley rats
The prevalence of obesity is increasing worldwide, both in developed and developing nations and a high fat diet is one of the main factors. It is known that obesity also increase the predisposition to other diseases such as diabetes and cardiovascular diseases through the involvement of various m...
Saved in:
| Main Author: | |
|---|---|
| Format: | Thesis |
| Language: | English |
| Published: |
2014
|
| Subjects: | |
| Online Access: | http://psasir.upm.edu.my/id/eprint/75993/1/FSTM%202014%2036%20-%20IR.pdf |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | The prevalence of obesity is increasing worldwide, both in developed and developing
nations and a high fat diet is one of the main factors. It is known that obesity also
increase the predisposition to other diseases such as diabetes and cardiovascular diseases
through the involvement of various metabolic pathways. The lack of anti-obesity drugs
and the popularity of alternative and complementary medicine has encouraged research
in finding phytochemical strategies to this multifaceted disease. In this study, extracts of
Morinda citrifolia leaf of different maturity and extracted with different ethanol
concentrations were assessed for their bioactivity (total phenolic content, DPPH
scavenging activity, inhibitory effects on pancreatic and lipoprotein lipase activity) as
potential anti-obesity agents. Mature leaves extracted with 60% ethanol, labeled as MLE
60 had the highest lipase inhibitory effect and was further analysed for its bioactive
content using 1H Nuclear Magnetic Resonance spectroscopy (1H NMR), Liquid
Chromatography Mass Spectroscopy (LCMS) and High Performance Liquid
Chromatography (HPLC). MLE 60 was found to contain flavonoids, including catechin,
kaempherol and rutin. The anti-obesity effect of the same extract was subsequently
assessed for the prevention and treatment of obesity, in vivo. In the preventive study,
lean Sprague- Dawley rats were fed a high fat diet (HFD) with or without MLE 60 for
12 weeks and assessed for weight gain, adiposity, appetite, fecal fat excretion and
plasma biochemistry. Supplementation of MLE 60 in the HFD group prevented weight
gain (98.6-129.6%) as compared to the control HFD only group (176.3%), reduced
adiposity (3.45-4.04%) as compared to the control obese group (6.98%), increased fecal
fat excretion (11.39-19.58%) compared to 5.34% for the control group, without any
effect on appetite. The plasma biochemistry profiles were improved, with a marked
decrease in total triglycerides, leptin and insulin levels. For the treatment study, HFD
induced obese Sprague- Dawley rats were treated with MLE 60 post feeding with a HFD
for 12 weeks. Similar parameters as the preventive study were measured. After 9 weeks of treatment, no significant weight loss was achieved in any of the treated group,
including the group treated with the standard control drug Orlistat®, though positive
effects were observed on adiposity, fecal fat content, plasma lipids, insulin and leptin
levels. The inducement of obesity and treatment with MLE 60 on metabolic alterations
were then further elucidated using a 1H NMR based metabolomics approach, where the
urine and serum of obese and lean rats were compared for biomarkers associated with
HFD induced obesity. Multivariate analysis, including the projections to latent
structures-discriminant analysis (OPLS-DA) was used for biomarkers identification.
Discriminating metabolites involved were products of various metabolic pathways,
including glucose metabolism and TCA cycle (lactate, 2-Oxoglutarate, citrate, succinate,
pyruvate, acetate), amino acid metabolism (alanine, 2-hydroxybutyrate), choline
metabolism (betaine), creatinine metabolism (creatinine) and gut microbiome
metabolism (hippurate, phenylacetylglycine, dimethylamine, trigonelline). Treatment
with MLE 60, specifically at 250 mg/kg, resulted in significant improvement in the
metabolic perturbations caused by HFD induced obesity as demonstrated by the
proximity of the treated group to the normal group in the OPLS-DA score plot and the
change in trajectory movement of the diseased group towards the healthy group upon
treatment. A relative quantification of discriminating metabolites showed improvements
in the treated groups. This study reports on the potential anti-obesity effect of MLE 60,
based on its lipase inhibiting ability as reflected as by the increase fecal fat content and
its positive effect on pro obesity factors including leptin and insulin. It also confirms that
consumption of a HFD caused metabolic perturbations other than traditionally studied
parameters, which can be improved by the supplementation of plant extracts like MLE
60 and 1H NMR based metabolomics can be a good tool in obesity research. |
|---|