- Title
- Lipid pathway regulation in high fat diet induced insulin resistance and prevention by Sutherlandia frutescens
- Creator
- Nnolum-Orji, Ngozi Francisca
- Subject
- Insulin -- Physiological effect
- Subject
- Fatty acids -- Metabolism Lipids in human nutrition
- Date Issued
- 2018
- Date
- 2018
- Type
- Thesis
- Type
- Masters
- Type
- MSc
- Identifier
- http://hdl.handle.net/10948/33442
- Identifier
- vital:32873
- Description
- Excessive dietary fats are key players in the development of insulin resistance (IR). These fatty acids alter the normal lipid metabolic processes, mostly lipolysis and lipogenesis, through hormonal and transcriptional regulation, and in part, through alterations in the gut microbiota composition and their secretion of short-chain fatty acids (SCFAs). In this regard, extensive knowledge on the development (at different time points) of this deregulation of lipid metabolism by high-fat feeding, and the control thereof, is necessary to identify early biomarkers of metabolic diseases such as IR and T2DM, and provide new pharmacological and behavioural lifestyle intervention strategies. In a previous study at NMMU, male Wister rats developed IR within 56 days of chronic intake of a high-fat diet (HFD), while the group that consumed the same HFD supplemented with aqueous extracts of Sutherlandia frutescens (HFD+SF) were protected from IR (Mackenzie, 2009). The present study investigated the role of the gut microbiota via SCFA secretion, and that of the lipid pathways in the observed IR with high-fat feeding, and in the prevention with S. frutescens supplementation. These were done through study of the over-time (days 28, 56 and 86) regulation of gut-derived SCFAs in the liver and plasma samples, as well as the regulation of lipolytic and lipogenic parameters in the liver and adipose tissue samples of these rats. Quantification of SCFAs was carried out using GC-MS technique, while qRT-PCR was used for estimation of the expression levels of genes coding for lipolytic and lipogenic enzymes and transcriptional/regulatory factors. The results obtained showed no role of gut-derived SCFAs as substrates for lipid metabolism in the study rats. Also, gene expression of the lipolytic enzyme (HSL) did not provide evidence of a causative role of adipose lipolysis in the development of observed IR in HFD rats. However, the importance of adipose tissue insulin sensitivity to the maintenance of normal lipolytic rates was indicated in Sutherlandia treated rats. On the other hand, over-time decrease in the gene expression of lipogenic enzymes (ACC and FAS) in the liver and adipose tissues of HFD rats imply that deregulation of lipogenesis contributed to IR in these rats. Conversely, stimulation of lipogenesis in the S. frutescens treated rats prevented the rats from developing IR. Furthermore, gene expression of the transcription factors (liver PPARalpha for lipolysis; and SREBP-1c and PPARgamma for lipogenesis) correlate these observations. Leptin gene expression supports its effect on lipolysis but not lipogenesis, while gene expressions of SCFA receptors correlate FFAR2, but not FFAR3, to lipogenesis and lipolysis.
- Format
- xxi, 150 leaves
- Format
- Publisher
- Nelson Mandela University
- Publisher
- Faculty of Science
- Language
- English
- Rights
- Nelson Mandela University
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NMU School of BioMolecular and Chemical Sciences
| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | SOURCE1 | NGOZI FRANCISCA NNOLUM-ORJI.pdf | 3 MB | Adobe Acrobat PDF | View Details Download |