TY - JOUR
T1 - High-fat diets rich in medium- versus long-chain fatty acids induce distinct patterns of tissue specific insulin resistance
AU - De Vogel-van den Bosch, Johan
AU - van den Berg, Sjoerd A.A.
AU - Bijland, Silvia
AU - Voshol, Peter J.
AU - Havekes, Louis M.
AU - Romijn, Hans A.
AU - Hoeks, Joris
AU - van Beurden, Denis
AU - Hesselink, Matthijs K.C.
AU - Schrauwen, Patrick
AU - van Dijk, Ko Willems
N1 - Funding Information:
Supported by TI food and Nutrition (Wageningen, The Netherlands). The study sponsor was not involved in the design or performance of the study.
PY - 2011/4
Y1 - 2011/4
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/79952532668
U2 - 10.1016/j.jnutbio.2010.03.004
DO - 10.1016/j.jnutbio.2010.03.004
M3 - Article
C2 - 20655716
AN - SCOPUS:79952532668
SN - 0955-2863
VL - 22
SP - 366
EP - 371
JO - Journal of Nutritional Biochemistry
JF - Journal of Nutritional Biochemistry
IS - 4
ER -
