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Leptin pulsatility in formerly obese women.
Geltrude Mingrone1, Melania Manco, Luigi Granato
1Department of Internal Medicine, CNR Centro di Fisiopatologia dello Shock, Catholic University, School of Medicine, Rome, Italy. gmingrone@rm.unicatt.it
Summary
Bilio-pancreatic diversion (BPD) improves insulin sensitivity and reduces leptin levels, restoring leptin pulsatility and increasing growth hormone (GH) secretion in obese patients. This metabolic shift enhances fatty acid oxidation and reverses insulin resistance.
Area of Science:
- Metabolic Surgery
- Endocrinology
- Obesity Research
Background:
- Morbid obesity is associated with altered plasma leptin and growth hormone (GH) profiles.
- Bilio-pancreatic diversion (BPD) is a bariatric surgery causing significant lipid malabsorption.
Purpose of the Study:
- To investigate the effects of BPD on plasma leptin and GH profiles and pulsatility in morbidly obese subjects.
- To assess the impact of BPD on glucose uptake, lipid oxidation, and related gene expression.
Main Methods:
- Studied plasma leptin and GH profiles and pulsatility before and 14 months after BPD.
- Assessed whole-body glucose uptake using euglycemic-hyperinsulinemic clamp.
- Measured 24-hour lipid oxidation and skeletal muscle ACC2 mRNA and malonyl-CoA levels.
Main Results:
- BPD decreased leptin diurnal variation and increased its pulsatility index.
- BPD significantly increased plasma GH acrophase and pulsatility index.
- Whole-body glucose uptake nearly doubled, while 24-hour lipid oxidation decreased but represented a higher percentage of intake; ACC2 mRNA and malonyl-CoA reduced.
- Leptin changes negatively correlated with glucose uptake changes; free fatty acids and glucose/insulin ratio predicted leptin variations.
Conclusions:
- BPD may reverse insulin and leptin resistance, restoring leptin pulsatility and increasing GH secretion.
- Reduced malonyl-CoA synthesis due to inhibited ACC2 mRNA expression leads to increased fatty acid oxidation post-BPD.
- The observed increase in GH secretion is likely due to reduced circulating leptin levels, which normally inhibit GH secretion.