Title
High-fat diets rich in medium- versus long-chain fatty acids induce distinct patterns of tissue specific insulin resistance
Author
de Vogel-van den Bosch, J.
van den Berg, S.A.A.
Bijland, S.
Voshol, P.J.
Havekes, L.M.
Romijn, H.A.
Hoeks, J.
van Beurden, D.
Hesselink, M.K.C.
Schrauwen, P.
van Dijk, K.W.
Publication year
2011
Abstract
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 µmol 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±8.5 µmol min-1 kg-1, P<05) and a lower peripheral glucose disappearance (75.7±7.8 vs. 93.4±12.4 µmol 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. © 2011 Elsevier Inc.
Subject
Life
MHR - Metabolic Health Research
EELS - Earth, Environmental and Life Sciences
Nutrition
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http://resolver.tudelft.nl/uuid:e605a949-bb5f-4a28-a40c-b8d600b54428
TNO identifier
428129
ISSN
0955-2863
Source
Journal of Nutritional Biochemistry, 22 (4), 366-371
Document type
article