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High-Fat Diet Alters Serum Fatty Acid Profiles in Obesity Prone Rats: Implications for In Vitro Studies

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Lipids

Abstract

High-fat diets (HFD) are commonly used in rodents to induce obesity, increase serum fatty acids and induce lipotoxicity in various organs. In vitro studies commonly utilize individual free fatty acids (FFA) to study lipid exposure in an effort to model what is occurring in vivo; however, these approaches are not physiological as tissues are exposed to multiple fatty acids in vivo. Here we characterize circulating lipids in obesity-prone rats fed an HFD in both fasted and fed states with the goal of developing physiologically relevant fatty acid mixtures for subsequent in vitro studies. Rats were fed an HFD (60 % kcal fat) or a control diet (10 % kcal fat) for 3 weeks; liver tissue and both portal and systemic blood were collected. Fatty acid profiles and absolute concentrations of triglycerides (TAG) and FFA in the serum and TAG, diacylglycerol (DAG) and phospholipids in the liver were measured. Surprisingly, both systemic and portal serum TAG were ~40 % lower in HFD-fed compared to controls. Overall, compared to the control diet, HFD feeding consistently induced an increase in the proportion of circulating polyunsaturated fatty acids (PUFA) with a concomitant decline in monounsaturated fatty acids (MUFA) and saturated fatty acids (SFA) in both serum TAG and FFA. The elevations of PUFA were mostly attributed to increases in n-6 PUFA, linoleic acid and arachidonic acid. In conclusion, fatty acid mixtures enriched with linoleic and arachidonic acid in addition to SFA and MUFA should be utilized for in vitro studies attempting to model lipid exposures that occur during in vivo HFD conditions.

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Abbreviations

DAG:

Diacylglycerol(s)

FFA:

Non-esterified fatty acids

MAG:

Monoacylglycerol(s)

MUFA:

Monounsaturated fatty acid(s)

PL:

Phospholipids

PUFA:

Polyunsaturated fatty acid(s)

SFA:

Saturated fatty acid(s)

TAG:

Triacylglycerol(s)

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Acknowledgments

This work was funded by the National Institutes of Health [NIH R01DK088940 (JPT)] and 5T32 AR-48523-8 (EMM). This work was also completed in part with resources from the Research Services Department of the Harry S. Truman Memorial Veterans Hospital. We would like to thank Abiezer Blandon, Grace M. Meers, Melissa A. Linden and Justin A. Fletcher for their help and technical assistance with this study.

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Correspondence to John P. Thyfault.

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The authors have no conflicts of interest, financial or otherwise, to disclose for this research.

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Liu, TW., Heden, T.D., Matthew Morris, E. et al. High-Fat Diet Alters Serum Fatty Acid Profiles in Obesity Prone Rats: Implications for In Vitro Studies. Lipids 50, 997–1008 (2015). https://doi.org/10.1007/s11745-015-4061-5

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