Medium-chain triglyceride ameliorates insulin resistance and inflammation in high fat diet-induced obese mice
The aim of the present study was to investigate the in vivo effects of dietary medium-chain triglyceride (MCT) on inflammation and insulin resistance as well as the underlying potential molecular mechanisms in high fat diet-induced obese mice.
Male C57BL/6J mice (n = 24) were fed one of the following three diets for a period of 12 weeks: (1) a modified AIN-76 diet with 5 % corn oil (normal diet); (2) a high-fat control diet (17 % w/w lard and 3 % w/w corn oil, HFC); (3) an isocaloric high-fat diet supplemented with MCT (17 % w/w MCT and 3 % w/w corn oil, HF–MCT). Glucose metabolism was evaluated by fasting blood glucose levels and intraperitoneal glucose tolerance test. Insulin sensitivity was evaluated by fasting serum insulin levels and the index of homeostasis model assessment-insulin resistance. The levels of serum interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α were measured by ELISA, and hepatic activation of nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways was determined using western blot analysis.
Compared to HFC diet, consumption of HF-MCT did not induce body weight gain and white adipose tissue accumulation in mice. HFC-induced increases in serum fasting glucose and insulin levels as well as glucose intolerance were prevented by HF-MCT diet. Meanwhile, HF-MCT resulted in significantly lower serum IL-6 level and higher IL-10 level, and lower expression levels of inducible nitric oxide synthase and cyclooxygenase-2 protein in liver tissues when compared to HFC. In addition, HF-MCT attenuated HFC-triggered hepatic activation of NF-κB and p38 MAPK.
Our study demonstrated that MCT was efficacious in suppressing body fat accumulation, insulin resistance, inflammatory response, and NF-κB and p38 MAPK activation in high fat diet-fed mice. These data suggest that MCT may exert beneficial effects against high fat diet-induced insulin resistance and inflammation.
KeywordsMedium-chain triglyceride Insulin resistance Inflammation NF-κB p38 MAPK
- 1.Li Q, Zhong W, Qiu Y, Kang X, Sun X, Tan X, Zhao Y, Sun X, Jia W, Zhou Z (2013) Preservation of hepatocyte nuclear factor-4alpha contributes to the beneficial effect of dietary medium chain triglyceride on alcohol-induced hepatic lipid dyshomeostasis in rats. Alcohol Clin Exp Res 37:587–598CrossRefGoogle Scholar
- 5.Takeuchi H, Sekine S, Kojima K, Aoyama T (2008) The application of medium-chain fatty acids: edible oil with a suppressing effect on body fat accumulation. Asia Pac J Clin Nutr 17(Suppl 1):320–323Google Scholar
- 12.Zhao W, Varghese M, Vempati P, Dzhun A, Cheng A, Wang J, Lange D, Bilski A, Faravelli I, Pasinetti GM (2012) Caprylic triglyceride as a novel therapeutic approach to effectively improve the performance and attenuate the symptoms due to the motor neuron loss in ALS disease. PLoS One 7:e49191CrossRefGoogle Scholar
- 18.Tanti JF, Ceppo F, Jager J, Berthou F (2012) Implication of inflammatory signaling pathways in obesity-induced insulin resistance. Front Endocrinol (Lausanne) 3:181Google Scholar
- 23.Boisramé-Helms J, Delabranche X, Klymchenko A, Drai J, Blond E, Zobairi F, Mely Y, Hasselmann M, Toti F, Meziani F (2014) Lipid emulsions differentially affect LPS-induced acute monocytes inflammation: in vitro effects on membrane remodeling and cell viability. Lipids 49:1091–1099CrossRefGoogle Scholar
- 32.Kintscher U, Hartge M, Hess K, Foryst-Ludwig A, Clemenz M, Wabitsch M, Fischer-Posovszky P, Barth TF, Dragun D, Skurk T, Hauner H, Bluher M, Unger T, Wolf AM, Knippschild U, Hombach V, Marx N (2008) T-lymphocyte infiltration in visceral adipose tissue: a primary event in adipose tissue inflammation and the development of obesity-mediated insulin resistance. Arterioscler Thromb Vasc Biol 28:1304–1310CrossRefGoogle Scholar
- 38.Bastard JP, Maachi M, Lagathu C, Kim MJ, Caron M, Vidal H, Capeau J, Feve B (2006) Recent advances in the relationship between obesity, inflammation, and insulin resistance. Eur Cytokine Netw 17:4–12Google Scholar
- 44.Tang T, Zhang J, Yin J, Staszkiewicz J, Gawronska-Kozak B, Jung DY, Ko HJ, Ong H, Kim JK, Mynatt R, Martin RJ, Keenan M, Gao Z, Ye J (2010) Uncoupling of inflammation and insulin resistance by NF-kappaB in transgenic mice through elevated energy expenditure. J Biol Chem 285:4637–4644CrossRefGoogle Scholar
- 47.Hemi R, Yochananov Y, Barhod E, Kasher-Meron M, Karasik A, Tirosh A, Kanety H (2011) p38 mitogen-activated protein kinase-dependent transactivation of ErbB receptor family: a novel common mechanism for stress-induced IRS-1 serine phosphorylation and insulin resistance. Diabetes 60:1134–1145CrossRefGoogle Scholar