Reduction in circulating ghrelin concentration after maturation does not affect food intake

Area of Science:

• Endocrinology
• Metabolism
• Neuroscience

Background:

• Ghrelin, a hormone, is known for its potent appetite-stimulating effects.
• Previous studies on ghrelin-deficient mice yielded inconclusive results regarding its role in energy homeostasis due to potential developmental compensation.
• The precise physiological function of circulating ghrelin in regulating food intake and body weight remains to be fully elucidated.

Purpose of the Study:

• To investigate the role of circulating ghrelin in regulating food intake and energy balance.
• To overcome limitations of developmental compensation in previous ghrelin-null mouse models.
• To specifically assess the impact of reduced circulating ghrelin levels on feeding patterns and body weight regulation.

Main Methods:

• Utilized a transgenic mouse model (GPDTR-Tg) expressing the diphtheria toxin (DT) receptor under the ghrelin promoter.
• Administered DT to selectively ablate ghrelin-secreting cells in the stomach, reducing circulating ghrelin levels without affecting hypothalamic ghrelin.
• Monitored meal patterns, food intake, body weight, and responses to fasting and high-fat diets in DT-treated GPDTR-Tg mice.

Main Results:

• DT-treated GPDTR-Tg mice exhibited significantly reduced circulating ghrelin levels, even after fasting.
• No significant alterations were observed in meal patterns, meal sizes, or cumulative food intake.
• Mice showed normal starvation responses but increased fat utilization and slower weight gain when fed a high-fat diet.

Conclusions:

• Circulating ghrelin does not appear to be a critical regulator of feeding behavior or appetite.
• The study suggests that circulating ghrelin is more involved in the regulation of body weight maintenance, particularly in modulating fat metabolism and weight gain.
• These findings provide new insights into the complex roles of ghrelin in energy homeostasis.