Extra-adipocyte leptin release in human obesity and its relation to sympathoadrenal function

Area of Science:

• Neuroendocrinology
• Obesity Research
• Human Physiology

Background:

• The relationship between the sympathoadrenalmedullary system and leptin, an adipocyte hormone, remains debated.
• Previous research has not fully elucidated the non-adipocyte sources of leptin release.

Purpose of the Study:

• To investigate the link between the sympathoadrenalmedullary system and leptin secretion.
• To quantify whole body and regional leptin release, particularly from non-adipocyte sources like the brain.
• To explore the association between leptin release and brain neurotransmitter systems in lean versus obese men.

Main Methods:

• Arterial and central venous catheterization in 22 lean and 20 obese men.
• Measurement of norepinephrine and epinephrine spillover rates.
• Estimation of whole body leptin release via renal plasma leptin extraction.
• Simultaneous arteriovenous blood sampling to assess regional leptin release, including from the brain.
• Quantification of brain serotonin turnover and neuropeptide Y (NPY) overflow.

Main Results:

• Whole body leptin release was significantly higher in obese men (1,950 ng/min) compared to lean men (382 ng/min).
• Brain leptin release contributed substantially (>40%) to plasma leptin, being markedly greater in obese (935 ng/min) than lean men (160 ng/min).
• Obese men showed increased brain serotonin turnover and NPY overflow compared to lean men.

Conclusions:

• Leptin is released from multiple sites, including a significant contribution from the brain.
• Leptin release from the brain is elevated in obese individuals.
• Increased brain leptin release in obesity correlates with heightened brain serotonergic and NPY system activity.