Excess Folic Acid Increases Lipid Storage, Weight Gain, and Adipose Tissue Inflammation in High Fat Diet-Fed Rats.
Folic acid intake has increased to high levels in many countries, raising concerns about possible adverse effects, including disturbances to energy and lipid metabolism. Our aim was to investigate the effects of excess folic acid (EFA) intake compared to adequate folic acid (AFA) intake on metabolic health in a rodent model. We conducted these investigations in the setting of either a 15% energy low fat (LF) diet or 60% energy high fat (HF) diet. There was no difference in weight gain, fat mass, or glucose tolerance in EFA-fed rats compared to AFA-fed rats when they were fed a LF diet. However, rats fed EFA in combination with a HF diet had significantly greater weight gain and fat mass compared to rats fed AFA (p < 0.05). Gene expression analysis showed increased mRNA levels of peroxisome proliferator-activated receptor γ (PPARγ) and some of its target genes in adipose tissue of high fat-excess folic acid (HF-EFA) fed rats. Inflammation was increased in HF-EFA fed rats, associated with impaired glucose tolerance compared to high fat-adequate folic acid (HF-AFA) fed rats (p < 0.05). In addition, folic acid induced PPARγ expression and triglyceride accumulation in 3T3-L1 cells. Our results suggest that excess folic acid may exacerbate weight gain, fat accumulation, and inflammation caused by consumption of a HF diet.
Department of Agricultural, Food & Nutritional Science, University of Alberta, Edmonton, AB T6G2P5, Canada. kkelly1@ualberta.ca.
Karen B
KB
Kelly
Department of Agricultural, Food & Nutritional Science, University of Alberta, Edmonton, AB T6G2P5, Canada. jkennell@ualberta.ca.
John P
JP
Kennelly
Department of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Bilbao 48080, Spain. marta.ordonez87@gmail.com.
Marta
M
Ordonez
Department of Agricultural, Food & Nutritional Science, University of Alberta, Edmonton, AB T6G2P5, Canada. rn1@ualberta.ca.
Randal
R
Nelson
Department of Agricultural, Food & Nutritional Science, University of Alberta, Edmonton, AB T6G2P5, Canada. kmd4@ualberta.ca.
Kelly
K
Leonard
Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80206, USA. Sally.Stabler@ucdenver.edu.
Sally
S
Stabler
Department of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Bilbao 48080, Spain. antonio.gomez@ehu.es.
Antonio
A
Gomez-Muñoz
Department of Agricultural, Food & Nutritional Science, University of Alberta, Edmonton, AB T6G2P5, Canada. cjfield@ualberta.ca.
Catherine J
CJ
Field
Department of Agricultural, Food & Nutritional Science, University of Alberta, Edmonton, AB T6G2P5, Canada. rjacobs@ualberta.ca.|Department of Biochemistry, University of Alberta, Edmonton, AB T6G2R7, Canada. rjacobs@ualberta.ca.
René L
RL
Jacobs
D041721:3T3-L1 Cells; D000273:Adipose Tissue / Q000187:drug effects; D000818:Animals; D001786:Blood Glucose; D004041:Dietary Fats / Q000008:administration & dosage* / Q000009:adverse effects; D005492:Folic Acid / Q000008:administration & dosage* / Q000009:adverse effects*; D007249:Inflammation / Q000139:chemically induced*; D050356:Lipid Metabolism; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015430:Weight Gain / Q000187:drug effects*
D001786:Blood Glucose; D004041:Dietary Fats; D012333:RNA, Messenger; D005492:Folic Acid
adipose tissue; folic acid; metabolic syndrome; obesity
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