Caloric Restriction-Induced Decreases in Dopamine Receptor Availability are Associated with Leptin Concentration

Area of Science:

• Neuroendocrinology
• Obesity Research
• Radioligand Imaging

Background:

• Previous studies indicate reduced dopamine (DA) type 2 and 3 receptor (D2/3R) binding potential (BPND) after Roux-en-Y-gastric bypass.
• The role of calorie restriction without weight loss on D2/3R BPND and its neuroendocrine regulation remains unclear.

Purpose of the Study:

• To investigate if calorie restriction, independent of significant weight loss, alters D2/3R BPND in individuals with obesity.
• To determine if observed changes in D2/3R BPND are associated with neuroendocrine factors like insulin, leptin, and ghrelin.

Main Methods:

• Fifteen females with obesity underwent a very-low-calorie diet (VLCD) for approximately 10 days.
• Fasting insulin, leptin, acyl ghrelin, and glucose levels were measured, along with insulin sensitivity and disposition index via the oral-minimal model (OMM).
• Positron emission tomography (PET) scanning with [18F]fallypride was used to estimate regional D2/3R BPND in the caudate, putamen, ventral striatum, hypothalamus, and substantia nigra (SN).

Main Results:

• The VLCD resulted in a slight weight reduction (-3 kg) and significant decreases in insulin, glucose, and leptin.
• Acyl ghrelin and OMM-derived measures showed no significant changes.
• A significant decrease in SN D2/3R BPND was observed, with a trend towards reduction in other regions.
• Decreased leptin concentration strongly predicted the change in D2/3R BPND across all studied regions (P ≤ 0.004).

Conclusions:

• Very-low-calorie diet in obesity is associated with reduced regional D2/3R availability, potentially due to increased endogenous dopamine.
• These neuroendocrine changes, particularly decreased leptin, precede significant weight loss and are linked to alterations in D2/3R availability.