title: A physiological characterization of the Cafeteria diet model of metabolic syndrome in the rat.
abstract: Many promising findings from pre-clinical research have failed to translate to the clinic due to their inability to incorporate human disease co-morbidity. A variety of rodent diets and feeding durations are currently used in models of human metabolic syndrome, obesity and diabetes. One model, the Cafeteria (CAF) diet, makes use of grocery store-purchased food items that more closely approximate the human ultra-processed diet than commercial high-fat or high-sugar rodent diets. The present study describes the development of metabolic syndrome in rats fed a CAF diet as well as the recovery of metabolic syndrome following a healthy "lifestyle" change. In addition, we explored the effects of CAF diet on spatial learning and memory and on neuroinflammation. Three-week old male Sprague-Dawley rats were fed a CAF diet for three months that consisted of 16 highly palatable human food items along with standard chow and a 12% sucrose solution to mimic soda consumption. Thereafter, a sub-group of CAF diet rats was switched to a chow diet (SWT) for one month. Both CAF and SWT groups were compared to control rats maintained on a standard chow diet (SD). Prior to the diet switch, CAF and SWT animals developed features akin to metabolic syndrome. Both groups of rats displayed significant abdominal obesity with increased visceral adiposity, hyperinsulinemia, glucose intolerance and dyslipidemia with elevated serum triglyceride levels and reduced HDL cholesterol. Switching to a chow diet for one month completely reversed these features in SWT animals. Although acquisition of the Barnes maze was not affected by the CAF diet, these animals exhibited greater hippocampal neuroinflammation compared to both SD and SWT rats as assessed by Iba1 staining. These results demonstrate that the CAF diet is very effective in creating metabolic syndrome with hippocampal inflammation in rats over a relatively short time span. This model may be of great heuristic importance in determining potential reversibility of metabolic and cerebrovascular pathologies across the lifespan and as a co-morbid factor in other disease models such as stroke.
authors.affiliation: Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada; Canadian Partnership for Stroke Recovery, Ottawa, ON, Canada.
authors.forename: Mariana
authors.initials: M
authors.lastname: Gomez-Smith
authors.affiliation: Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada; Canadian Partnership for Stroke Recovery, Ottawa, ON, Canada.
authors.forename: Sudhir
authors.initials: S
authors.lastname: Karthikeyan
authors.affiliation: Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada; Canadian Partnership for Stroke Recovery, Ottawa, ON, Canada.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Jeffers
authors.affiliation: Sunnybrook Research Institute, Toronto, ON, Canada; Medical Biophysics, University of Toronto, Toronto, ON, Canada.
authors.forename: Rafal
authors.initials: R
authors.lastname: Janik
authors.affiliation: Sunnybrook Research Institute, Toronto, ON, Canada.
authors.forename: Lynsie A
authors.initials: LA
authors.lastname: Thomason
authors.affiliation: Sunnybrook Research Institute, Toronto, ON, Canada; Medical Biophysics, University of Toronto, Toronto, ON, Canada; Canadian Partnership for Stroke Recovery, Ottawa, ON, Canada.
authors.forename: Bojana
authors.initials: B
authors.lastname: Stefanovic
authors.affiliation: Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada; Faculty of Medicine, Memorial University, St. John's, NL, Canada; Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Canadian Partnership for Stroke Recovery, Ottawa, ON, Canada. Electronic address: dcorbett@uottawa.ca.
authors.forename: Dale
authors.initials: D
authors.lastname: Corbett
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight; D002135:Calcium-Binding Proteins / Q000378:metabolism; D004032:Diet / Q000009:adverse effects*; D004195:Disease Models, Animal; D002149:Energy Intake; D005951:Glucose Tolerance Test; D050152:Intra-Abdominal Fat / Q000000981:diagnostic imaging; D008279:Magnetic Resonance Imaging; D008297:Male; D018782:Maze Learning; D008659:Metabolic Diseases / Q000097:blood / Q000000981:diagnostic imaging / Q000503:physiopathology*; D008840:Microfilament Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D050151:Subcutaneous Fat / Q000000981:diagnostic imaging
chemical_list: C100745:Aif1 protein, rat; D002135:Calcium-Binding Proteins; D008840:Microfilament Proteins
keywords: Barnes maze; Cafeteria diet; Iba1; Inflammation; Metabolic syndrome; Rats