A high-fat diet induces rapid changes in the mouse hypothalamic proteome

Area of Science:

• Neuroscience
• Metabolic research
• Cell biology

Background:

• Prolonged high-fat diet (HFD) consumption is linked to obesity and insulin resistance.
• Even short-term HFD (3 days) can induce inflammation in the hypothalamus, a critical brain region for homeostasis.

Purpose of the Study:

• To investigate the proteomic changes in the hypothalamus after a 3-day HFD.
• To examine the direct effects of dietary fatty acids on neuronal cells and mitochondrial function.

Main Methods:

• Mice were fed either a low-fat diet (LFD) or HFD for 3 days.
• Proteomic analysis of the hypothalamus was performed, alongside glucose tolerance tests.
• Neuronal cells were treated with palmitic acid (PA) and oleic acid (OA) to assess mitochondrial morphology and dihydropyrimidinase-related protein 2 (DRP-2) levels.

Main Results:

• A 3-day HFD increased adiposity and glucose intolerance in mice.
• Hypothalamic proteomic analysis revealed 78 altered proteins, primarily related to cytoskeleton, synaptic plasticity, stress, and mitochondrial function.
• Palmitic acid (PA), but not oleic acid (OA), altered mitochondrial morphology and DRP-2 levels in neuronal cells.

Conclusions:

• A 3-day HFD significantly impacts the hypothalamic proteome, indicating cellular stress, altered synaptic plasticity, and mitochondrial dysfunction, but not inflammation.
• Long-chain saturated fatty acids, like PA, can damage neuronal function by affecting DRP-2 and mitochondrial morphology.
• These findings highlight the rapid impact of dietary fat on brain function.