The focus of this thesis was leptin and its role in the development of obesity and non-insulin-dependent diabetes mellitus (NIDDM). Studies in Psammomys obesus, a polygenic animal model of obesity and NIDDM, showed that ob gene expression and plasma leptin concentration correlated significantly with body weight, percentage body fat and plasma insulin concentration. In addition, plasma leptin concentrations were significantly elevated in insulin resistant Psammomys obesus independent of body weight. Dietary energy restriction from weaning in Psammomys obesus prevented excessive body weight gain, hyperleptinemia and hyperglycemia compared with ad libitum fed animals. Interestingly, 19% of the energy-restricted animals still developed hyperinsulinemia and tended to have increased plasma leplin compared with normoinsulinemic energy-restricted Psammomys obesus. Fasting for 24 hours significantly reduced plasma leptin concentration in lean, insulin-sensitive but not obese, insulin-resistant P. obesus, suggesting a dysregulation in the response of leptin to acute caloric deprivation in these animals.
The effects of leptin administration to P. obesus were also investigated. Single daily intraperitoneal injection of 5 mg leptin/kg body weight for 14 days had no significant effect in lean or obese P. obesus. This dose had previously been shown to rapidly and significantly reduce food intake and body weight in ob/ob and wild-type mice, suggesting relative leptin resistance in P. obesus. Acute (8 hour) effects of administration of 5 mg leptin/kg body weight were also investigated. No significant effects on food intake or plasma insulin were detected, however blood glucose concentrations were significantly elevated in obese, glucose intolerant P. obexus, suggesting an exacerbation of insulin resistance in susceptible animals. Treatment of lean, healthy P. obesus with 45 mg leptin/kg body weight/day for 7 days resulted in significant decreases in food intake and percentage body fat, showing that the leptin resistance observed in this species could be overcome by the administration of very large doses of leptin.
In another study, leplin was shown to significantly inhibit maximal insulin binding to isolated adipocytes, suggesting that leptin may respresent an important link between obesity and NIDDM. Links between aspects of obesity and NIDDM and polymorphisms in the ob and p3-adrencrgic receptor genes were also investigated in two human populations.
| Identifer | oai:union.ndltd.org:ADTP/217135 |
| Date | January 1997 |
| Creators | Walder, Ken, mikewood@deakin.edu.au |
| Publisher | Deakin University. School of Nutrition and Public Health |
| Source Sets | Australiasian Digital Theses Program |
| Language | English |
| Detected Language | English |
| Rights | http://www.deakin.edu.au/disclaimer.html), Copyright Ken Walder |
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