scholarly journals Dietary Folic Acid and Fat Alter Metabolism of Multiple Vitamins in Mice

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1778-1778
Author(s):  
Keri Barron ◽  
Natalia Krupenko

Abstract Objectives To determine how low and high folic acid (FA) intake, combined with either low or high-fat diets, affects other vitamins in mouse liver and plasma. Methods C57BL/6NHsd mice were placed on one of six diets at weaning and maintained for 16 weeks. The diets varied in their fat content and FA levels: low fat (14% kcal from fat) vs high fat (58% kcal from fat) with 3 different FA levels- 0 ppm FA (FD), 2 ppm FA (Ctrl), 12 ppm (FS). Diets were matched for all other vitamins and minerals. Untargeted metabolomics analysis of plasma and snap-frozen liver samples was conducted at Metabolon®. Results In liver, excess dietary folic acid on a low-fat diet resulted in significantly increased levels of pantothenate, α-tocopherol, FA and several folate metabolites. When FA was over-supplemented in combination with a high fat (HF) diet, α-tocopherol was increased along with several nicotinate and pantothenate metabolites. Interestingly, the HF-FD and -FS diets demonstrated similar effects. These diets resulted in significantly decreased levels of riboflavin, thiamine, vitamin A, and vitamin B6 metabolites while increasing levels of pantetheine metabolites. In plasma, fewer changes with significant differences were observed when mice were fed HF diets. Several nicotinate metabolites were significantly elevated due to the FD diet with no change due to FS. Additionally, there were no changes in pantothenate or riboflavin in the plasma. Interestingly, the HF- FD and -FS diets induced similar responses but in opposite directions in plasma vs liver. The plasma levels of thiamine, vitamin A, and vitamin B6 metabolites were all significantly increased due to both low and high FA, whereas in the liver they were decreased. Additionally, no changes in α-tocopherol were seen in plasma, but the HF-FD diet raised γ/β-tocopherol levels over 2-fold despite equal amounts of vitamin E among all diets. Conclusions Untargeted metabolomic analysis revealed that diets with too high or too low folate affect other vitamins both in liver and plasma. These effects were further modulated by dietary fat levels. The HF-FD and -FS diets had significant impact on vitamins A, B1, B2, B3, B5, B6, B9 and E, along with their related derivatives, which may have serious implications for multiple metabolic pathways. Funding Sources NIH.

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Megha Murali ◽  
Carla Taylor ◽  
Peter Zahradka ◽  
Jeffrey Wigle

Background and Objective: Arterial stiffness is recognized as being an independent predictor of incipient vascular disease associated with obesity and metabolic syndrome. In obese subjects, the decrease in the plasma level of adiponectin, an anti-diabetic and anti-atherogenic adipokine, is well known. Hence the aim of our study was to examine the effect of loss of adiponectin on the development of arterial stiffness in response to a high fat diet. Methods and Results: Male 8-week old adiponectin knockout (APN KO) and C57BL/6 (control) mice were fed a high fat diet (60% Calories from fat) for 12 weeks to induce obesity and insulin resistance (n=10/group). APN KO and C57BL/6 mice were fed a low fat diet (10% Calories from fat) and used as lean controls (n=10/group). After 12 weeks on the high fat diet, the APN KO mice weighed significantly more than the C57BL/6 mice (45.1±1.3 g vs 40.1±1.1 g, p=0.0008) but there was no difference in the final weights between genotypes fed the low fat diet. APN KO mice on both high and low fat diets for 12 weeks developed insulin resistance as measured by oral glucose tolerance test (Area under curve (AUC) mmol/L х min = 437±70 and 438±57) as compared to the C57BL/6 mice fed low or high fat diets (AUC mmol/L х min = 251±27 and 245±43). Arterial stiffness was determined by Doppler pulse wave velocity analysis of the femoral artery. Pulse wave velocity was increased in APN KO mice fed a high fat diet relative to those fed the low fat diet (12.56±0.78 cm/s vs 9.47±0.95 cm/s, p=0.0035; n=8-10). Pulse wave velocity was not different between C57BL/6 control mice on the low or high fat diets (10.63±0.73 cm/s and 10.86±0.50 cm/s), thus revealing that only mice deficient in adiponectin developed arterial stiffness in response to high fat diet. Conclusions: Potentiation of the vascular stiffness in diet-induced obese APN KO mice indicates that adiponectin has a role in modulating vascular structure and the APN KO mouse models the vascular changes that occur in human obesity and metabolic disorders. Morphometric analysis of the aortic tissues for vessel thickness and expression of extracellular proteins will further validate the potential role of adiponectin on the maintenance of arterial elasticity in addition to its known effect on eNOS mediated vasoprotection.


1992 ◽  
Vol 263 (4) ◽  
pp. R785-R789 ◽  
Author(s):  
T. A. Buchanan ◽  
J. S. Fisler ◽  
S. Underberger ◽  
G. F. Sipos ◽  
G. A. Bray

To determine whether whole body insulin sensitivity differs between a rat strain that does not (S 5B/Pl) and a strain that does [Osborne-Mendel (OM)] become obese when eating a high-fat diet, we performed euglycemic clamp studies in animals from each strain during low- and high-fat feeding. Clamps were performed after 2 days ("initial clamp") and 9 days ("final clamp") on each diet. Plasma glucose and insulin levels during the final 60 min of initial and final clamps were similar in S 5B/Pl and OM rats regardless of diet. Insulin sensitivity, measured as the glucose clearance rate during the final 60 min of the clamp, averaged 35 +/- 3 ml.kg-1.min-1 in S 5B/Pl rats after 2 days on a low-fat diet. This did not change significantly during an additional 7 days on the low-fat diet. The high-fat diet was associated with a 13% reduction in insulin sensitivity after 2 days and a 30% reduction after 9 days in S 5B/Pl rats. OM rats exhibited similar patterns of insulin sensitivity during low- and high-fat diets, albeit at lower insulin sensitivity overall (P < 0.0005 vs. S 5B/Pl). Mean glucose clearance after 2 days on the low-fat diet was 27 +/- 2 mg.kg-1.min-1 and did not change significantly during seven more days of low-fat feeding. The high-fat diet was associated with a 19% reduction in glucose clearance after 2 days and a 38% reduction after 9 days in OM rats. The magnitude of reduction in insulin sensitivity during high-fat diets did not differ significantly between strains.(ABSTRACT TRUNCATED AT 250 WORDS)


2007 ◽  
Vol 86 (5) ◽  
pp. 1316-1322 ◽  
Author(s):  
Marie-Pierre St-Onge ◽  
Bradley R Newcomer ◽  
Steven Buchthal ◽  
Inmaculada Aban ◽  
David B Allison ◽  
...  

1999 ◽  
Vol 277 (1) ◽  
pp. R279-R285 ◽  
Author(s):  
Mihai Covasa ◽  
Robert C. Ritter

When rats are maintained on high-fat diets, digestive processes adapt to provide for more efficient digestion and absorption of this nutrient. Furthermore, rats fed high-fat diets tend to consume more calories and gain more weight than rats on a low-fat diet. We hypothesized that, in addition to adaptation of digestive processes, high-fat maintenance diets might result in reduction of sensitivity to the satiating effects of fat digestion products, which inhibit food intake by activating sensory fibers in the small intestine. To test this hypothesis we measured food intake after intestinal infusion of oleic acid or the oligosaccharide maltotriose in rats maintained on a low-fat diet or one of three high-fat diets. We found that rats fed high-fat diets exhibited diminished sensitivity to satiation by intestinal infusion of oleic acid. Sensitivity to the satiation effect of intestinal maltotriose infusion did not differ between groups maintained on the various diets. Reduced sensitivity to oleate infusion was specifically dependent on fat content of the diet and was not influenced by the dietary fiber or carbohydrate content. These results indicate that diets high in fat reduce the ability of fat to inhibit further food intake. Such changes in sensitivity to intestinal fats might contribute to the increased food intake and obesity that occur with high-fat diet regimens.


2000 ◽  
Vol 84 (2) ◽  
pp. 175-184 ◽  
Author(s):  
Yoko Takahashi ◽  
Takashi Ide

We examined the effect of dietary fats rich in n-3 polyunsaturated fatty acids (PUFA) on mRNA levels in white and brown adipose tissues in rats. Four groups of rats were fed on a low-fat diet (20 g safflower oil/kg) or a high-fat diet (200 g/kg) containing safflower oil, which is rich in n-6 PUFA (linoleic acid), or perilla (α-linolenic acid) or fish oil (eicosapentaenoic and docosahexaenoic acids), both of which are rich in n-3 PUFA, for 21 d. Energy intake was higher in rats fed on a high-safflower-oil diet than in those fed on low-fat or high-fish-oil diet, but no other significant differences were detected among the groups. Perirenal white adipose tissue weight was higher and epididymal white adipose tissue weight tended to be higher in rats fed on a high-safflower-oil diet than in those fed on a low-fat diet. However, high-fat diets rich in n-3 PUFA, compared to a low-fat diet, did not increase the white adipose tissue mass. High-fat diets relative to a low-fat diet increased brown adipose tissue uncoupling protein 1 mRNA level. The increases were greater with fats rich in n-3 PUFA than with n-6 PUFA. A high-safflower-oil diet, compared to a low-fat diet, doubled the leptin mRNA level in white adipose tissue. However, high-fat diets rich in n-3 PUFA failed to increase it. Compared to a low-fat diet, high-fat diets down-regulated the glucose transporter 4 mRNA level in white adipose tissue. However, the decreases were attenuated with high-fat diets rich in n-3 PUFA. It is suggested that the alterations in gene expression in adipose tissue contribute to the physiological activities of n-3 PUFA in preventing body fat accumulation and in regulating glucose metabolism in rats.


1994 ◽  
Vol 124 (2) ◽  
pp. 188-195 ◽  
Author(s):  
Joanne R. Lupton ◽  
Xiao-Qing Chen ◽  
Wenche Frølich ◽  
Gretchen L. Schoeffler ◽  
Matthew L. Peterson

2013 ◽  
Vol 305 (1) ◽  
pp. R68-R77 ◽  
Author(s):  
Joram D. Mul ◽  
Denovan P. Begg ◽  
Jason G. Barrera ◽  
Bailing Li ◽  
Emily K. Matter ◽  
...  

Overconsumption of a high-fat diet promotes weight gain that can result in obesity and associated comorbidities, including Type 2 diabetes mellitus. Consumption of a high-fat diet also alters gut-brain communication. Glucagon-like peptide 1 (GLP-1) is an important gastrointestinal signal that modulates both short- and long-term energy balance and is integral in maintenance of glucose homeostasis. In the current study, we investigated whether high-fat diets (40% or 81% kcal from fat) modulated the ability of the GLP-1 receptor (GLP-1r) agonists exendin-4 (Ex4) and liraglutide to reduce food intake and body weight. We observed that rats maintained on high-fat diets had a delayed acute anorexic response to peripheral administration of Ex4 or liraglutide compared with low-fat diet-fed rats (17% kcal from fat). However, once suppression of food intake in response to Ex4 or liraglutide started, the effect persisted for a longer time in the high-fat diet-fed rats compared with low-fat diet-fed rats. In contrast, centrally administered Ex4 suppressed food intake similarly between high-fat diet-fed and low-fat diet-fed rats. Chronic consumption of a high-fat diet did not change the pharmacokinetics of Ex4 but increased intestinal Glp1r expression and decreased hindbrain Glp1r expression. Taken together, these findings demonstrate that dietary composition alters the temporal profile of the anorectic response to exogenous GLP-1r agonists.


1994 ◽  
Vol 71 (06) ◽  
pp. 755-758 ◽  
Author(s):  
E M Bladbjerg ◽  
P Marckmann ◽  
B Sandström ◽  
J Jespersen

SummaryPreliminary observations have suggested that non-fasting factor VII coagulant activity (FVII:C) may be related to the dietary fat content. To confirm this, we performed a randomised cross-over study. Seventeen young volunteers were served 2 controlled isoenergetic diets differing in fat content (20% or 50% of energy). The 2 diets were served on 2 consecutive days. Blood samples were collected at 8.00 h, 16.30 h and 19.30 h, and analysed for triglycerides, FVII coagulant activity using human (FVII:C) or bovine thromboplastin (FVII:Bt), and FVII amidolytic activity (FVIPAm). The ratio FVII:Bt/FVII:Am (a measure of FVII activation) increased from fasting levels on both diets, but most markedly on the high-fat diet. In contrast, FVII: Am (a measure of FVII protein) tended to decrease from fasting levels on both diets. FVII:C rose from fasting levels on the high-fat diet, but not on the low-fat diet. The findings suggest that high-fat diets increase non-fasting FVII:C, and consequently may be associated with increased risk of thrombosis.


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