Brain-specific chemokine FAM19A5 induces hypothalamic inflammation

Area of Science:

• Neuroscience
• Immunology
• Endocrinology

Background:

• The cytokine-like protein FAM19A5 is abundant in the brain, yet its specific functions remain largely uncharacterized.
• Hypothalamic proopiomelanocortin (POMC) and neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurons regulate energy balance and are implicated in inflammatory responses.

Purpose of the Study:

• To investigate the role of FAM19A5 in the hypothalamus, particularly in response to inflammatory stimuli like tumor necrosis factor-alpha (TNF-α).
• To determine the effects of FAM19A5 manipulation on feeding behavior, body weight, and inflammatory signaling within the hypothalamus.

Main Methods:

• Examined FAM19A5 expression in mouse hypothalamic POMC and NPY/AgRP neurons, as well as microglia.
• Utilized FAM19A5 knockdown and intracerebroventricular (ICV) administration in mice.
• Assessed TNF-α-induced changes in feeding, body weight, inflammatory factors, and neuronal activation (c-fos).

Main Results:

• Hypothalamic FAM19A5 expression was significantly upregulated by TNF-α.
• FAM19A5 knockdown attenuated TNF-α-induced anorexia, weight loss, and inflammatory factor expression.
• ICV FAM19A5 administration mimicked TNF-α effects, causing anorexia, weight loss, hyperthermia, and increased inflammatory factors.
• FAM19A5 injection elevated c-fos activation and POMC mRNA levels in POMC neurons.

Conclusions:

• FAM19A5 is a key mediator of inflammatory responses in the hypothalamus.
• FAM19A5 influences feeding behavior and body weight regulation through hypothalamic pathways.
• The findings highlight FAM19A5 as a potential therapeutic target for inflammatory conditions affecting the brain.