Diurnal variations of adiponectin levels have been studied in normal-weight men and in diabetic and nondiabetic obese subjects, but no data have been reported in obese subjects after weight loss. We collected blood samples at 1-h intervals over 24 h from seven severely obese subjects before and after massive weight loss consequent to surgical operation (bilio-pancreatic diversion [BPD]) to measure adiponectin, insulin, glucose, and cortisol levels. Insulin sensitivity was assessed by euglycemic-hyperinsulinemic clamp (M value). Studies of diurnal variations and pulsatility of adiponectin, insulin, and cortisol were performed. The pulsatility index (PI) of adiponectin increased after BPD from 0.04 to 0.11 g/min (P ‫؍‬ 0.01). Insulin PI significantly increased after the operation (1.50 vs. 1.08 pmol ⅐ l -1 ⅐ min -1 , P ‫؍‬ 0.01), while cortisol PI did not significantly change. The adiponectin clearance rate changed from 0.001 ؎ 10 ؊4 ⅐ min ؊1 before BPD to 0.004 ؎ 8 ⅐ 10 ؊4 ⅐ min ؊1 after BPD (P ‫؍‬ 0.03). Insulin clearance increased from 0.006 ؎ 6 ⅐ 10 ؊4 ⅐ min ؊1 before BPD to 0.009 ؎ 4 ⅐ 10 ؊4 ⅐ min ؊1 after BPD (P ‫؍‬ 0.02). The M value doubled after surgery (27.08 ؎ 8.5 vs. 53.34 ؎ 9.3 mol ⅐ kg FFM ؊1 ⅐ min ؊1 ; P < 0.001) becoming similar to the values currently reported for normal-weight subjects. In conclusion, in formerly severely obese subjects, weight loss paired with the reversibility of insulin resistance restores homeostatic control of the adiponectin secretion, contributing to the reduction of cardiovascular risk already described in these patients. Diabetes 53:939 -947, 2004 R ecent advances in the biology of adipose tissue indicate that it is not simply an energy storage organ but also a secretory organ, producing a variety of bioactive substances, including leptin, tumor necrosis factor (TNF)-␣, resistin, and adiponectin, thus acting as an endocrine organ. These adipocyte-specific proteins, termed adipokines, present a variety of local, peripheral, and central effects. It has been shown that the adipose tissue secretes metabolites such as nonesterified fatty acids (NEFAs), glycerol, and hormones (1) in a pulsatile fashion, similar to leptin. The regulation of this pulsatility seems to be mediated by hormonal (2) or neural (2,3) mechanisms. Insulin plays a critical role in the regulation of both the hormonal and metabolic activity of the adipocytes.Higher absolute leptin levels coupled with blunted relative diurnal excursions and dampened pulsatility have been found in obese subjects (4). Similarly, insulin pulse amplitudes are restored (5). Weight loss restores leptin pulsatility (4) and reverses insulin resistance (6).Recently, diurnal variations in circulating levels of adiponectin in diabetic and nondiabetic obese subjects (7) and in healthy normal-weight male human subjects have been investigated (3). Hotta et al. (7) did not observe any daily changes in circulating levels of adiponectin in obesity. In normal-weight subjects, Gavrila et al. (3) found an ultradian pulsatility as well as a diu...

Plasma leptin and growth hormone (GH) profile and pulsatility have been studied in morbidly obese subjects before and 14 months after bilio-pancreatic diversion (BPD), a bariatric technique producing massive lipid malabsorption. The maximum leptin diurnal variation (acrophase) decreased (10.27+/-1.70 vs. 22.60+/-2.79 ng x ml(-1); P=0.001), while its pulsatility index (PI) increased (1.084+/-0.005 vs. 1.050+/-0.004 ng x ml(-1) x min(-1); P=0.02) after BPD. Plasma GH acrophase increased (P=0.0001) from 0.91+/-0.20 to 4.58+/-0.80 microg x l(-1) x min(-1) after BPD as well as GH PI (1.70+/-0.13 vs. 1.20+/-0.04 microg x l(-1) x min(-1); P=0.024). Whole-body glucose uptake (M), assessed by euglycemic-hyperinsulinemic clamp, almost doubled after BPD (from 0.274+/-0.022 to 0.573+/-0.027 mmol x kgFFM(-1) x min(-1); P<0.0001), while 24 h lipid oxidation was significantly (P<0.0001) reduced (131.94+/-35.58 vs. 44.56+/-15.10 g). However, the average lipid oxidation was 97.2+/-3.1% (P<0.01) of the metabolizable lipid intake after the bariatric operation, while it was 69.2+/-8.5% before. After the operation, skeletal muscle ACC2 mRNA decreased (P<0.0001) from 452.82+/-76.35 to 182.45+/-40.69% of cyclophilin mRNA as did the malonyl-CoA (from 0.28+/-0.02 to 0.16+/-0.01 nmol x g(-1); P<0.0001). Leptin changes negatively correlated with M changes (R2=0.69, P<0.001). In a stepwise regression (R2=0.87, P=0.0055), only changes in 24 h free fatty acids (B=0.105+/-0.018, P=0.002) and glucose/insulin ratio (B=0.247+/-0.081, P=0.029) were the best predictors of leptin variations. In conclusion, the reversion of insulin resistance after BPD might allow reversal of leptin resistance, restoration of leptin pulsatility, and consequent inhibition of ACC2 mRNA expression, translating to a reduced synthesis of malonyl-CoA, which, in turn, results in increased fatty acid oxidation. Finally, since leptin inhibits GH secretion, a reduction of circulating leptin levels might have produced an increase in GH secretion, as observed in our series.