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Investigation Into the Regulation of Hormone Sensitive Lipase and Lipoprotein Lipase Activity and Gene Expression in Human Adipose Tissue.

Rashid, Najat. (2000) Investigation Into the Regulation of Hormone Sensitive Lipase and Lipoprotein Lipase Activity and Gene Expression in Human Adipose Tissue. Doctoral thesis, University of Surrey (United Kingdom)..

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Coronary heart disease (CHD) is the leading cause of death worldwide. Its prevalence is determined by increasing age, gender (male > female), heredity and lifestyle factors. The latter include diet, which may lead to elevated blood lipids including cholesterol, triacylglycerol, non-esterified fatty acids, and to reduced insulin sensitivity. All of these have been implicated as contributing to the metabolic environment that predisposes to CHD. Two enzymes, hormone sensitive lipase (HSL) and lipoprotein lipase (LPL) are responsible for the mobilisation and clearance of fatty acids respectively. A sensitive reverse transcriptase-polymerase chain reaction technique was developed previously in our lab for the measurement of LPL-mRNA, but in this thesis further development of this method is presented. To enable the assessment of the regulation of HSL and LPL enzymes in human adipose tissue in different nutritional or disease states, the development of a new reverse transcriptase-polymerase chain reaction procedure for measurement of HSL-mRNA was developed. The acute regulation of both lipase activity and gene expression in the fasting and fed state, using adipose tissue biopsies from eight male subjects with type 2-diabetes mellitus (2-DM) were compared with matched control male subjects. The findings indicated that type 2-DM subjects had significantly lower LPL-mRNA levels than control subjects in both fasting (61% of control values; p<0.002), and post-prandial (43% of control values; p<0.002) states. In addition, HSL-mRNA levels were significantly lower in type 2-DM subjects compared with control subjects (p<0.01) in both fasting (34% of control values) and post-prandial (32% of control values) states. However, HSL-mRNA levels were significantly higher in the post-prandial compared with the fasting state (p<0.01) for both diabetic (fasting was 21% of postprandial) and control subjects (fasting was 19% of post-prandial). These findings suggest LPL-mRNA accumulates in the fasting state and is utilised in the fed state. On the other hand, HSL-mRNA accumulates in the fed and is utilised in the fasted state. Epidemiological studies suggest that regional body fat distribution may be a better predictor of cardiovascular disease than the actual degree of adiposity. Many studies and reviews have shown an association between upper-body obesity (omental obesity) and insulin resistance, and the risk of developing type 2-DM and CHD. However, although widely postulated the causative link between insulin resistance and central adiposity lacks evidence from mechanistic studies. This thesis describes a study comparing subcutaneous and omental adipose tissue obtained from 10 non-obese premenopausal women. There were no differences in HSL or LPL activity or LPL-mRNA levels but omental cells were 61% smaller than those from the subcutaneous depot (P= 0.007). The similar levels of lipase activities in different regions found in the present study may have resulted from the subjects being young, non-obese and female.

Item Type: Thesis (Doctoral)
Divisions : Theses
Authors : Rashid, Najat.
Date : 2000
Additional Information : Thesis (Ph.D.)--University of Surrey (United Kingdom), 2000.
Depositing User : EPrints Services
Date Deposited : 06 May 2020 14:38
Last Modified : 06 May 2020 14:47

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