title: 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: 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.
  
  
  OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neuroanatomy, Jagiellonian University, Krakow, Poland.
authors.forename: Zuzanna
authors.initials: Z
authors.lastname: Setkowicz
authors.affiliation: Military Institute of Aviation Medicine, Warsaw, Poland.
authors.forename: Agata
authors.initials: A
authors.lastname: Gaździńska
authors.affiliation: Department of Neuroanatomy, Jagiellonian University, Krakow, Poland.
authors.forename: Joanna J
authors.initials: JJ
authors.lastname: Osoba
authors.affiliation: Department of Neuroanatomy, Jagiellonian University, Krakow, Poland.
authors.forename: Karolina
authors.initials: K
authors.lastname: Karwowska
authors.affiliation: Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Majka
authors.affiliation: Mossakowski Medical Research Centre Polish Academy of Sciences, Warsaw, Poland; Faculty of Electronics and Information Technology, Warsaw University of Technology, Warsaw, Poland.
authors.forename: Jarosław
authors.initials: J
authors.lastname: Orzeł
authors.affiliation: Mossakowski Medical Research Centre Polish Academy of Sciences, Warsaw, Poland; Faculty of Electronics and Information Technology, Warsaw University of Technology, Warsaw, Poland.
authors.forename: Bartosz
authors.initials: B
authors.lastname: Kossowski
authors.affiliation: Mossakowski Medical Research Centre Polish Academy of Sciences, Warsaw, Poland; Faculty of Electronics and Information Technology, Warsaw University of Technology, Warsaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Bogorodzki
authors.affiliation: Department of Neuroanatomy, Jagiellonian University, Krakow, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Janeczko
authors.affiliation: Military Institute of Aviation Medicine, Warsaw, Poland.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Wyleżoł
authors.affiliation: Military Institute of Aviation Medicine, Warsaw, Poland.
authors.forename: Stefan P
authors.initials: SP
authors.lastname: Gazdzinski
mesh_terms: D000818:Animals; D001835:Body Weight; D059305:Diet, High-Fat / Q000009:adverse effects*; D004151:Dipeptides / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D008297:Male; D018782:Maze Learning; D008569:Memory Disorders / Q000209:etiology / Q000378:metabolism; D009765:Obesity / Q000209:etiology / Q000473:pathology* / Q000523:psychology; D009929:Organ Size; D017208:Rats, Wistar; D065852:Spatial Memory
chemical_list: D004151:Dipeptides; C027172:isospaglumic acid; D018698:Glutamic Acid