Aberrant bone marrow-derived microglia in the hypothalamus may dysregulate appetite in diabetes

Area of Science:

• Neuroscience
• Immunology
• Metabolic Disorders

Background:

• Bone marrow-derived cells (BMDCs) are crucial for microglia formation in the hypothalamus.
• Microglia regulate vital functions, including food intake.
• Diabetes mellitus is known to impair immune cell function, including BMDCs.

Purpose of the Study:

• To investigate the functional impact of diabetes on BMDCs and their role in hypothalamic microglia.
• To determine if impaired BMDC function contributes to hyperphagia observed in diabetes.

Main Methods:

• Bone marrow transplantation from GFP transgenic mice into streptozotocin-induced diabetic wild-type mice.
• Confirmation of BMDC engraftment and differentiation into microglia within the brain parenchyma, even with an intact blood-brain barrier (BBB).
• Comparative analysis of hypothalamic BMDC numbers and response to fasting between diabetic and non-diabetic mice, including chimeric models.

Main Results:

• Diabetic mice exhibited hyperphagia (excessive appetite).
• Fewer BMDCs were found in the hypothalamus of diabetic mice, with a diminished response to fasting compared to non-diabetic controls.
• Chimeric mice with diabetic BMDCs showed a reduced response to fasting, confirming the cell-autonomous effect of diabetes on BMDCs.

Conclusions:

• Diabetic BMDCs exhibit impaired function and reduced response to fasting signals within the hypothalamus.
• The dysfunction of diabetic BMDCs, leading to altered microglial activity, is a potential mechanism underlying hyperphagia in diabetes.
• These findings highlight a critical link between metabolic health, immune cell function, and appetite regulation.