I investigated the effects of continuous administration of fluoxetine, a serotonin reuptake inhibitor, on energy expenditure, body temperature, and thyroid and catecholamine metabolism during weight reduction using a very low calorie diet (VLCD, Optifast, 1757 kJ/day) followed by a balanced deficit diet (BDD, 5016 kJ/day). Fluoxetine (60 mg/day by mouth, n = 10) or placebo (n = 10) were administered during 3 weeks of inpatient VLCD followed by 8 weeks of outpatient BDD in a double-blind, randomized design. A similar amount of weight was lost in both groups during the VLCD, but by the end of the BDD total weight loss in the fluoxetine group was significantly greater (11.0 $ pm$ 1.1 kg vs. 7.0 $ pm$ 1.0 kg, mean $ pm$ SEM, p $<$ 0.015). Resting metabolic rate (RMR) increased by 4.4 $ pm$ 1.8% (p $<$ 0.01) in the fluoxetine group but did not change in the placebo group during the first week of the VLCD, but subsequently decreased significantly in both groups as dieting continued. However, RMR remained consistently higher in the fluoxetine group for the duration of the VLCD period. No further change in RMR occurred in either group during the BDD period. The thermic effect of food did not change after VLC dieting plus fluoxetine or placebo treatment. Body temperature increased within 2 days of fluoxetine treatment by a mean of 0.3$ sp circ$C, p $<$ 0.025 and remained elevated throughout the VLCD but was unchanged in the placebo group. VLCD therapy reduced serum levels of T$ sb3$, free T$ sb3$ Index and 24-hour urinary excretion of dopamine, norepinephrine, metanephrine and normetanephrine equivalently in both groups. A thermogenic effect of fluoxetine is demonstrated in humans for the first time. The anorectic effect of fluoxetine may be related to its temperature elevating effect.

We questioned whether adrenergic amines extracted from the Seville orange Citrus Aurantium (CA) increases metabolic rate and enhance the thermic response to a 1.7MJ mixed meal (TEF) in lean and obese men and women; the latter had upper-body obesity, a condition associated with defective TEF, attributed to altered SNS. Nine lean (7M, 2F; BMI: 23 +/- 1 k g/m 2; waist circumference: 78 +/- 2 cm) and 13 obese (4M, 9F; BMI: 35 +/- 1 kg/m2; waist circumference: 105 +/- 3 cm) subjects were studied. With CA: (1) RMR increased more in men vs women (94 vs 42 kJ over 5 h), independently of body composition; (2) urinary epinephrine excretion increased in both groups and dopamine only in men. A 17% lower TEF in obese subjects was no longer significant when controlled for gender. By contrast, there was an effect of gender on TEF that remained significant when adjusted for measures of obesity. Women had a lower TEF that increased to values no longer different from men with CA. CA did not affect TEF in men. CA had no cardiovascular effects. Thus, CA ingestion increased thermogenesis by 4% above RMR and enhanced the lower TEF of women by 29% (46kJ).

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Copies of author's previously published articles inserted. / Bibliography: leaves 103-119. / viii, 199, [87] leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Aims to understand at the transcriptional level how 1,25-dihydroxyvitamin D3 up-regulates the mitochondrial cytochrome P450 enzyme. / Thesis (Ph.D.)--University of Adelaide, Dept. of Biochemistry, 1998?