Degree Name

Doctor of Philosophy (PhD)


Department of Biomedical Science - Faculty of Health & Behavioural Sciences


Overweight and obesity have reached epidemic proportions and appetite control may be important for its clinical management. Leptin is a plasma protein secreted from adipose tissue that is involved in body weight regulation. The role of leptin in regulating human appetite is not well established. Human feeding studies report that an increased dietary carbohydrate to fat ratio is associated with increased circulating leptin concentrations compared to a decreased dietary carbohydrate to fat ratio. These investigations have generally used diets with extreme variations in macronutrient intake that do not represent normal patterns of consumption. Whether less extreme variations in macronutrient intake have similar effects on circulating leptin and whether there is a relationship with satiety under these conditions is not established. The overall aim of this research was to determine the potential clinical relevance of the effects of altering the dietary carbohydrate to fat ratio on circulating leptin concentrations. Methods: Three short-term controlled human feeding studies were conducted involving 68 female subjects (age 37 - 9 (SD) yrs, BMI 26.8 - 4.1 kg/m2). Study 1 and Study 2 were single-blind parallel design trials where realistic high carbohydrate (carbohydrate:fat= 60:20) or high fat (carbohydrate:fat= 40:40) iso-caloric diets were provided. Study 3 was a double-blind cross-over trial where high carbohydrate (carbohydrate:fat= 60:20) and extreme high fat (carbohydrate:fat= 25:55) diets were provided. The primary outcomes were fasting leptin concentrations and subjective satiety measured on a multi-dimensional and single-dimension visual analogue scales. In Study 3 ad libitum intake was also assessed at a post-intervention buffet breakfast. Two-way repeated measures analysis of variance was used to analyse the effect of the intervention diets over time on the outcome measures. Results: There was no between group difference in fasting leptin concentrations when realistic high carbohydrate and high fat controlled diets were consumed in Study 1 and Study 2 (p>0.4). This finding was similar when leptin concentrations were adjusted for body composition. Within subjects, changes in recent dietary carbohydrate and fat intake predicted a decrease in leptin concentrations during the intervention, but effects were small. A weak linear relationship between leptin concentrations and subjective satiety score was detected in Study 1 (p=0.06), but no relationship was detected in Study 2 and Study 3 (p>0.7). In Study 3 the more extreme high fat diet reduced leptin concentrations by 21% relative to the high carbohydrate diet (time*diet interaction, p<0.01). There was no influence of this difference in leptin concentration on ad libitum energy or macronutrient intake at the buffet breakfast (95% CI for difference in energy intake -411kJ to 190kJ). Conclusions: Circulating leptin concentrations are influenced by dietary carbohydrate to fat ratio such that decreasing the carbohydrate content of the diet results in decreased circulating leptin concentrations. However, the potential clinical relevance of this finding to the management of overweight and obesity is likely to be limited as i) extreme dietary patterns are necessary to detect this effect, ii) leptin concentrations were not related to subjective satiety score and iii) differences in leptin concentrations did not influence ad libitum food intake. Further research is necessary to confirm these findings over longer time frames, with different subject groups, twenty four hour blood sampling and ad libitum intake over the entire day.

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