Hindbrain insulin controls feeding behavior.

Area of Science:

• Neuroscience
• Metabolism
• Endocrinology

Background:

• Insulin, primarily known for its pancreatic role in glucose regulation, is also suggested to be produced in the brain.
• The specific functions and locations of brain-derived insulin, especially in the hindbrain, remain poorly understood.
• Understanding brain insulin is crucial for metabolic and feeding behavior research.

Purpose of the Study:

• To investigate insulin expression in the dorsal vagal complex (DVC) of the hindbrain.
• To determine the role of DVC-derived insulin in regulating feeding behavior and metabolism.
• To examine how diet-induced obesity affects insulin expression in the DVC.

Main Methods:

• Utilized transgenic mice (RipHER-cre) for optogenetic stimulation of insulin-producing neurons.
• Employed in situ hybridization to confirm insulin expression in DVC cells.
• Administered a central insulin receptor antagonist to block insulin signaling.
• Used virogenetic knockdown to reduce insulin gene expression in the hindbrain.

Main Results:

• Detected insulin gene expression in the DVC, with increased levels in diet-induced obesity, contrasting with hypothalamic changes.
• Optogenetic activation of DVC insulin neurons induced hyperphagia, which was blocked by an insulin receptor antagonist.
• Insulin gene knockdown in the DVC reduced food intake in mice on a high-fat diet.

Conclusions:

• Hindbrain insulin and its producing cells are significantly involved in energy homeostasis.
• DVC insulin plays a critical role in modulating feeding behavior, particularly under conditions of obesity.
• These findings highlight a novel role for hindbrain insulin in metabolic regulation.