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

Abstract

BackgroundObesity 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.AimTo 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.MethodsTwenty 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.ResultsObese 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).ConclusionLong-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.

Effects of post-training administration of LY341495, as a mGluR2/3 antagonist on spatial memory deficit in rats fed with high-fat diet

“…Unlike most previous studies; our results established that spatial learning ability in HFD-treated rats remained intact. Our results show similarity to a study by Zuzanna and colleagues (2), who observed that long-term HFD for 12 months improved the learning ability. They also found that prolonged HFD consumption leads to higher hippocampal volume and higher hippocampal metabolite concentrations, possibly due to increased ketone bodies levels in the blood.…”

“…Consuming a HFD has long been known to rise the risk of some diseases such as obesity, diabetes mellitus, metabolic syndrome, and also Alzheimer's disease and some types of cognitive impairment in humans and rodents (1). Although many studies repeatedly have shown that high-fat diet is associated with learning and memory impairment, it has recently been reported that high-fat diet improves memory 3 in Wistar rats (2). These observations show a contradictory effect of high-fat diet on learning and memory.…”

Intragastric balloon therapy leads to normalization of brain magnetic resonance spectroscopic markers of diabetes in morbidly obese patients

“…Concentrations of tNAA, but not m‐Ins, have been shown to be affected by diet . This may be important, as it is likely that dietary changes accompany IGB insertion.…”

Long-Term Consumption of High-Fat Diet in Rats: Effects on Microglial and Astrocytic Morphology and Neuronal Nitric Oxide Synthase Expression

“…Upon post-mortem assessment, HFCD-fed rats had 38 % larger fat deposits than CTRLs, as evaluated by volume of epididymal fat, a known marker of fat deposits in rats (Setkowicz et al 2015). At the time of sacrifice, blood samples were also taken, and serum interleukin 6 levels were assessed with a rat IDELISA IL-6 ELISA kit (Empire Genomics) according to manufacturer protocol, to determine whether an inflammatory state is present.…”