A high fat diet alters metabolic and bioenergetic function in the brain: A magnetic resonance spectroscopy study

Abstract

Diet-induced obesity and associated metabolic effects can lead to neurological dysfunction and increase the risk of developing Alzheimer's disease (AD) and Parkinson's disease (PD). Despite these risks, the effects of a high-fat diet on the central nervous system are not well understood. To better understand the mechanisms underlying the effects of high fat consumption on brain regions affected by AD and PD, we used proton magnetic resonance spectroscopy ((1)H-MRS) to measure neurochemicals in the hippocampus and striatum of rats fed a high fat diet vs. normal low fat chow. We detected lower concentrations of total creatine (tCr) and a lower glutamate-to-glutamine ratio in the hippocampus of high fat rats. Additional effects observed in the hippocampus of high fat rats included higher N-acetylaspartylglutamic acid (NAAG), and lower myo-inositol (mIns) and serine (Ser) concentrations. Post-mortem tissue analyses revealed lower phosphorylated AMP-activated protein kinase (pAMPK) in the striatum but not in the hippocampus of high fat rats. Hippocampal pAMPK levels correlated significantly with tCr, aspartate (Asp), phosphoethanolamine (PE), and taurine (Tau), indicating beneficial effects of AMPK activation on brain metabolic and energetic function, membrane turnover, and edema. A negative correlation between pAMPK and glucose (Glc) indicates a detrimental effect of brain Glc on cellular energy response. Overall, these changes indicate alterations in neurotransmission and in metabolic and bioenergetic function in the hippocampus and in the striatum of rats fed a high fat diet.

Keywords: Brain metabolism; Diet-induced obesity; High-fat; Imaging; Magnetic resonance spectroscopy.

Figure 1

Sample voxels chosen for ¹H-MRS (A-D) and an MR spectrum (E). Regions of interest for hippocampus (A, C) and striatum (B, D) as identified on anatomical MRI taken from the coronal (top row) and sagittal (bottom row) planes. (E) Sample ¹H-MR spectrum from hippocampus of a chow-fed rat. Prominent neurochemical peaks are labeled. Cr = creatine, PCr = phosphocreatine, Gln = glutamine, Glu = glutamate, GPC = Glycerophosphocholine, PC = phosphocholine, mIns = myo-inositol, Lac = lactate, MM = macromolecules, NAA = N-acetylaspartate, Tau = taurine.

Figure 2

Between-groups differences in selected neurochemicals measured with ¹H-MRS. Glc, Glu, and Gln in the hippocampus (A) and the striatum (B). The ratio of Glu to Gln was significantly decreased in the hippocampus of the high fat group. NAAG, mIns, NAA, and Ser in the hippocampus (C) and the striatum (D). NAAG was significantly greater in the hippocampus of the high fat group, while mIns and Ser were significantly lower. Cr, PCr and tCr in the hippocampus (E) and the striatum (F). tCr was significantly lower in the hippocampus of the high fat group. Control = Chow; HF = High-fat; Data are expressed as means + S.E.M. See Table 1 for p values.

Figure 3

Western blot quantification of proteins in hippocampal (A) and striatal (B) tissue. pAMPK/AMPK was significantly lower in the high fat rats than the control rats in striatum, but not in hippocampus; PGC1α levels revealed a non-significant trend to be lower in the high fat group in striatum, but not in hippocampus; there was no significant difference of GFAP, NRF-1, TFAM between high fat rats and control rats in either striatum or hippocampus. Control = Chow; HF = High-fat; Data are expressed as means + S.E.M. *p=0.005.