Restoration of Adiponectin Pulsatility in Severely Obese
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 µg/min (P = 0.01). Insulin PI significantly increased after the operation (1.50 vs. 1.08 pmol · l · min, P = 0.01), while cortisol PI did not significantly change. The adiponectin clearance rate changed from 0.001 ± 10 · min before BPD to 0.004 ± 8 · 10 · min after BPD (P = 0.03). Insulin clearance increased from 0.006 ± 6 · 10 · min before BPD to 0.009 ± 4 · 10 · min after BPD (P = 0.02). The M value doubled after surgery (27.08 ± 8.5 vs. 53.34 ± 9.3 µmol · kg_FFM · min; 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.

Recent 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)-α, 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 in a pulsatile fashion, similar to leptin. The regulation of this pulsatility seems to be mediated by hormonal or neural 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. Similarly, insulin pulse amplitudes are restored. Weight loss restores leptin pulsatility and reverses insulin resistance.

Recently, diurnal variations in circulating levels of adiponectin in diabetic and nondiabetic obese subjects and in healthy normal-weight male human subjects have been investigated. Hotta et al. did not observe any daily changes in circulating levels of adiponectin in obesity. In normal-weight subjects, Gavrila et al. found an ultradian pulsatility as well as a diurnal variation in adiponectin plasma levels with a significant decline at night, reaching a nadir in the early morning. However, to the best of our knowledge no data have been reported in the literature regarding the diurnal pulsatility of adiponectin in obese subjects after weight loss.

In contrast, a few studies have investigated the effect of weight loss on fasting adiponectin plasma levels. Fasting circulating adiponectin concentrations have been reported to increase after weight loss obtained by either gastric partition in obese subjects or Roux-en-Y gastric bypass surgery in morbidly obese subjects. More recently, a dietary intervention study showed that weight loss in obese nondiabetic subjects was associated with a significant increase in circulating levels of adiponectin.

Since no data are available in the literature concerning the ultradian rhythm and pulsatility of adiponectin in obese subjects before and after weight loss, the present study was undertaken to evaluate the 24-h adiponectin profile in morbidly obese subjects before and after weight loss as a result of malabsorptive bariatric surgery. In addition, a number of determinants of the daily adiponectin pattern were also investigated.