High-fat diets rich in medium- versus long-chain fatty acids induce distinct patterns of tissue specific insulin resistance

被引：23

作者：

De Vogel-van den Bosch, Johan ^{[2
,3
]}

van den Berg, Sjoerd A. A. ^{[1
,2
]}

Bijland, Silvia ^{[1
]}

Voshol, Peter J. ^{[5
]}

Havekes, Louis M. ^{[6
,7
,8
]}

Romijn, Hans A. ^{[5
]}

Hoeks, Joris ^{[3
]}

van Beurdee, Denis ^{[2
,3
]}

Hesselink, Matthijs K. C. ^{[4
]}

Schrauwen, Patrick ^{[2
,3
]}

van Dijk, Ko Willems ^{[1
,2
,6
]}

机构：

[1] Leiden Univ, Med Ctr, Dept Human Genet, NL-2300 RC Leiden, Netherlands

[2] Top Inst Food & Nutr, NL-6700 AN Wageningen, Netherlands

[3] Maastricht Univ, Med Ctr, Dept Human Biol, NL-6229 ER Maastricht, Netherlands

[4] Maastricht Univ, Med Ctr, Dept Human Movement Sci, NL-6229 ER Maastricht, Netherlands

[5] Leiden Univ, Med Ctr, Dept Endocrinol & Metab Dis, NL-2300 RC Leiden, Netherlands

[6] Leiden Univ, Med Ctr, Dept Gen Internal Med, NL-2300 RC Leiden, Netherlands

[7] Netherlands Org Appl Sci Res BioSci, Gaubius Lab, NL-2333 CK Leiden, Netherlands

[8] Leiden Univ, Med Ctr, Dept Cardiol, NL-2300 RC Leiden, Netherlands

来源：

JOURNAL OF NUTRITIONAL BIOCHEMISTRY | 2011年 / 22卷 / 04期

关键词：

RAT SKELETAL-MUSCLE; FOOD-INTAKE; ENERGY-EXPENDITURE; DIFFERENTIAL OXIDATION; DIABETES-MELLITUS; GLUCOSE; TRIGLYCERIDE; MICE; DECREASE; LIVER;

D O I：

10.1016/j.jnutbio.2010.03.004

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Excess dietary long-chain fatty acid (LCFA) intake results in ectopic lipid accumulation and insulin resistance. Since medium-chain fatty acids (MCFA) are preferentially oxidized over LCFA, we hypothesized that diets rich in MCFA result in a lower ectopic lipid accumulation and insulin resistance compared to diets rich in LCFA. Feeding mice high-fat (HF) (45% kcal fat) diets for 8 weeks rich in triacylglycerols composed of MCFA (HFMCT) or LCFA (HFLCT) revealed a lower body weight gain in the HFMCT-fed mice. Indirect calorimetry revealed higher fat oxidation on HFMCT compared to HFLCT (0.011.0 +/- 0.0007 vs. 0.0096 +/- 0.0015 kcal/g body weight per hour, P<.05). In line with this, neutral lipid immunohistochemistry revealed significantly lower lipid storage in skeletal muscle (0.05 +/- 0.08 vs. 0.30 +/- 0.23 area%, P<.05) and in liver (0.9 +/- 0.4 vs. 6.4 +/- 0.8 area%, P<.05) after HFMCT vs. HFLCT, while ectopic fat storage in low fat (LF) was very low. Hyperinsulinemic euglycemic clamps revealed that the HFMCT and HFLCT resulted in severe whole body insulin resistance (glucose infusion rate: 53.1 +/- 6.8, 50.8 +/- 15.3 vs. 124.6 +/- 25.4 mu mol min(-1) kg(-1), P<.001 in HFMCT, HFLCT and LF-fed mice, respectively). However, under hyperinsulinemic conditions, HFMCT revealed a lower endogenous glucose output (22.6 +/- 8.0 vs. 34.7 +/- 85 mu mol min(-1) kg(-1), P<.05) and a lower peripheral glucose disappearance (75.7 +/- 7.8 vs. 93.4 +/- 12.4 mu mol min(-1) kg(-1). P<.03) compared to HFLCT-fed mice. In conclusion, both HF diets induced whole body insulin resistance compared to LF. However, the HFMCT gained less weight, had less ectopic lipid accumulation, while peripheral insulin resistance was more pronounced compared to HFLCT. This suggests that HF-diets rich in medium- versus long-chain triacylglycerols induce insulin resistance via distinct mechanisms. (C) 2011 Elsevier Inc. All rights reserved.

引用

页码：366 / 371

页数：6

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