title: High-fat diets rich in medium- versus long-chain fatty acids induce distinct patterns of tissue specific insulin resistance.
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.
authors.affiliation: Top Institute Food and Nutrition, 6700 AN Wageningen, The Netherlands.
authors.forename: Johan
authors.initials: J
authors.lastname: De Vogel-van den Bosch
authors.forename: Sjoerd A A
authors.initials: SA
authors.lastname: van den Berg
authors.forename: Silvia
authors.initials: S
authors.lastname: Bijland
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Voshol
authors.forename: Louis M
authors.initials: LM
authors.lastname: Havekes
authors.forename: Hans A
authors.initials: HA
authors.lastname: Romijn
authors.forename: Joris
authors.initials: J
authors.lastname: Hoeks
authors.forename: Denis
authors.initials: D
authors.lastname: van Beurden
authors.forename: Matthijs K C
authors.initials: MK
authors.lastname: Hesselink
authors.forename: Patrick
authors.initials: P
authors.lastname: Schrauwen
authors.forename: Ko Willems
authors.initials: KW
authors.lastname: van Dijk
mesh_terms: D000818:Animals; D004041:Dietary Fats / Q000008:administration & dosage* / Q000494:pharmacology; D002149:Energy Intake; D005227:Fatty Acids / Q000008:administration & dosage*; D005947:Glucose / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014280:Triglycerides / Q000008:administration & dosage
chemical_list: D004041:Dietary Fats; D005227:Fatty Acids; D014280:Triglycerides; D005947:Glucose