Neuronal GHS-R Differentially Modulates Feeding Patterns under Normal and Obesogenic Conditions

Area of Science:

• Neuroscience
• Endocrinology
• Obesity Research

Background:

• Ghrelin, an orexigenic hormone, binds to GHS-R to increase food intake and promote obesity.
• Neuron-specific GHS-R knockout mice (Syn1-cre and AgRP-cre) show diet-dependent effects on body weight.
• Previous studies indicated varying anti-obesity effects between Syn1-cre and AgRP-cre lines under high-fat diet (HFD).

Purpose of the Study:

• To investigate the feeding behaviors of Syn1-cre and AgRP-cre GHS-R knockout mice under regular diet (RD) and HFD.
• To determine how GHS-R deletion in different neuronal populations affects meal patterns and energy homeostasis.
• To explore the relationship between feeding patterns, diet, and obesity development.

Main Methods:

• Utilized two neuron-specific GHS-R knockout mouse lines: pan-neuronal (Syn1-cre) and hypothalamic (AgRP-cre).
• Assessed feeding behaviors including meal number, size, duration, and frequency under RD and HFD.
• Analyzed the expression of key neuropeptides (NPY, Orexin) and receptors (CB1) in the hypothalamus.

Main Results:

• Syn1-cre mice exhibited reduced meal numbers and increased feeding duration under HFD, while AgRP-cre mice showed decreased meal duration under HFD.
• RD-fed Syn1-cre mice had decreased meal size, whereas RD-fed AgRP-cre mice had increased meal duration.
• Feeding pattern alterations were more pronounced in Syn1-cre mice and under HFD, suggesting neuronal GHS-R's role in diet-specific energy balance.

Conclusions:

• Neuronal GHS-R critically regulates energy homeostasis by modulating feeding patterns in a diet- and site-specific manner.
• Altered feeding patterns, such as slower eating during the active phase, may offer a strategy for obesity prevention.
• The findings highlight the complex interplay between ghrelin signaling, neuronal GHS-R, and feeding behavior in metabolic regulation.