SEAGLE, HELEN M., DAN H. BESSESEN, JAMES 0. HILL. Effects of sibutramine on resting metabolic rate and weight loss in overweight women. Obes Res. 1998; Sibutramine, a monoamine re-uptake inhibitor, has recently been approved by the Food and Drug Administration as a weight loss agent. Sibutramine lowers bodyweight in rodents by reducing energy intake and increasing energy expenditure. Sibutramine facilitates weight loss in human subjects, but it is not clear whether it acts on energy intake, energy expenditure, or both. The present study was a randomized clinical trial designed to assess the effects of sibutramine (at 10 or 30 mg/day) on body weight and resting metabolic rate (RMR). Forty-four overweight women were randomized to 1) placebo (n=15); 2) sibutramine at 10 mg/day (n=15) or, 3) sibutramine at 30 mg/day (n=14). All subjects were instructed to consume a 1200 kcaYday diet for 8 weeks while receiving drug or placebo. R M R was assessed by indirect calorimetry at baseline, at 3 hours after the first dose of drug (or placebo), and at the end of the 8-week weight-loss period. Sibutramine reduced body weightrelative to placebo, but there was no difference between weight loss on the two sibutramine doses. No significant differences in R M R between sibutramine and placebo were seen, either 3-hour post dose or after the 8-week weight-loss period. After the weight loss period, all groups were taken off medication and kept weight stable for another 4 weeks. R M R was measured again and was not different among groups. That there was no change in R M R when sibutramine was stopped further suggests that the drug does not directly affect RMR. In summary, while sibutramine was shown to be an effective weightloss agent over 8 weeks, we found no evidence that it increased RMR.

Objectives Changes in estrogen receptor (ER) expression likely underlie differential metabolic effects of estrogen in pre-and postmenopausal women. The aim of the current study was to determine whether ER gene expression in abdominal and femoral subcutaneous adipose tissue (SAT) was associated with age, menopause, or regional adiposity. Methods We studied pre-and post-menopausal (n=23 and 22, respectively; age 35–65 y) normal weight (mean±SD; BMI 23.7±2.5 kg/m2) women with similar total fat mass. Abdominal and femoral SAT ERα (ESR1) and ERβ (ESR2) mRNA expression was determined by qPCR. Results Total fat mass did not differ between pre-and postmenopausal women (22.7±5.3 vs. 21.7±5.3 kg). Compared to premenopausal women, ESR1 and the ratio of ESR1 to ESR2 were lower (p≤0.05) in postmenopausal abdominal and femoral SAT. ESR1 and ESR1:ESR2 were inversely associated with age in abdominal SAT (r=−0.380 and r=−0.463, respectively; p<0.05) and femoral SAT (r=−0.353 and r=−0.472, respectively; p<0.05). ESR2 was not related to age or menopause. The inverse association between ESR1 and age persisted after adjusting for trunk fat mass, estradiol, or leptin. Conclusion Among healthy pre-and postmenopausal women, increased age was associated with a decreased balance of ERα to ERβ in abdominal and femoral subcutaneous adipose tissue.

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