Does long-term high fat diet always lead to smaller hippocampi volumes, metabolite concentrations, and worse learning and memory? : a magnetic resonance and behavioral study in wistar rats

Background. Obesity is a worldwide epidemic with more than 600 million affected individuals. Human studies have demonstrated some alterations in brains of otherwise healthy obese individuals and elevated risk of neurodegenerative disease of old age; these studies have also pointed to slightly diminished memory and executive functions among healthy obese individuals. Similar findings were obtained in animal models of obesity induced by high fat diet. On the other hand, low carbohydrate high fat diets are currently promoted for losing weight (e.g., Atkin’s style diets). However, the long-term effects of such diets are not known. Additionally, high fat diets leading to (mild) ketonemia were shown to improve brain function in elderly humans and in some animal models. Aim. To evaluate the hypothesis that long-term use of a high fat diet was associated with decreases in spatial memory, smaller hippocampi and hippocampi metabolite concentrations in Wistar rats. Methods. Twenty five male Wistar rats were put on high fat diet (HFD; 60% calories from fat, 30% from carbohydrates) on their 55th day of life, while 25 control male rats (CONs) remained on chow. Adequate levels of essential nutrients were provided. Both groups underwent memory tests in 8-arm radial maze at 3rd, 6th, 9th, and 12th month. 1H magnetic resonance spectroscopy was employed to measure concentrations of tNAA (marker of neuronal integrity) at one month and one year, whereas MRI was used to evaluate hippocampal volumes. Results. Obese rats (OBRs) consumed similar amount of calories as CONs, but less proteins. However, their protein intake was within recommended amounts. Throughout the experiment OBRs had statistically higher concentrations of blood ketone bodies than CONs, but still within normal values. At post-mortem assessment, OBRs had 38% larger fat deposits than CONs (p<0.05), as evaluated by volume of epididymis fat, an acknowledged marker of fat deposits in rats. Contrary to our expectations, OBRs had better scores of memory behavioral tasks than CONs throughout the experiment. At one year, their hippocampi were by 2.6% larger than in CONs (p = 0.05), whereas concentration of tNAA was 9.8% higher (p = 0.014). Conclusion. Long-term HFD in our study resulted in better memory, larger hippocampal volumes, as well as higher hippocampal metabolite concentrations, possibly due to increased levels of blood ketone bodies. The results should be interpreted with caution, as results from animal models do not necessarily directly translate in human condition

The 42nd Symposium Chromatographic Methods of Investigating Organic Compounds : Book of abstracts

The 42nd Symposium Chromatographic Methods of Investigating Organic Compounds : Book of abstracts. June 4-7, 2019, Szczyrk, Polan

Exemplary parcellation of hippocampus: red = hippocampus, yellow = cortex, blue = cerebro-spinal fluid.

<p>Exemplary parcellation of hippocampus: red = hippocampus, yellow = cortex, blue = cerebro-spinal fluid.</p

Daily energy intake (A), changes in body weight during the experiment (B), changes in glucose blood levels (C), and changes in blood levels of ketone bodies (D) in controls and HFD-fed rats.

<p>*<i>P</i><0.05, ***<i>P</i><0.01. The “spikes” in levels of ketone bodies were caused by short-lived increases in concentrations of ketone bodies in single animals.</p

Hippocampal volumes (A) and concentration of metabolities: (B) N-acetylaspartate+N-acetylaspartylglutamate (tNAA), (C) glutamate (Glu) and (D) creatine+phosphocreatine (tCr).

<p>White and black graphs represent control (CONs) and high-fat high carbohydrate diet-treated (OBRs) animals, respectively. The graphs show median values with 25–75% variability range and maximal and minimal values. Decimal indexes indicate statistical significance of intergroup differences (Mann–Whitney U-test).</p

Exemplary proton spectrum with fitted baseline.

<p>Exemplary proton spectrum with fitted baseline.</p