Prolonged high fat diet reduces dopamine reuptake without altering DAT gene expression

Area of Science:

• Neuroscience
• Dietary Science
• Molecular Biology

Background:

• Diet-induced obesity (DIO) impacts dopamine signaling, including dopamine transporter (DAT) expression and dopamine reuptake.
• The precise timeline of diet-induced DAT alterations and their dependence on DIO remain unclear.

Purpose of the Study:

• To investigate the time-course of diet-induced changes in DAT function and expression.
• To determine if these changes are linked to the development of DIO.

Main Methods:

• Rats were fed high-fat (HFD) or low-fat (LFD) diets for 2 or 6 weeks.
• Striatal DAT function was assessed using fast-scan cyclic voltammetry.
• Membrane-associated DAT levels were quantified via Western blot.

Main Results:

• A deficit in dopamine reuptake was observed in HFD rats after 6 weeks, but not 2 weeks.
• Cocaine-induced dopamine release was attenuated in HFD rats.
• Total DAT protein remained unchanged, but a 50 kDa DAT isoform was reduced in synaptosomal membranes after 6 weeks of HFD.

Conclusions:

• Diet-induced alterations in dopamine reuptake can occur without changes in total DAT production.
• These dopamine signaling changes manifest even without the development of diet-induced obesity.