Enhancement of Muscle Mitochondrial Oxidative Capacity and Alterations in Insulin Action Are Lipid Species Dependent Potent Tissue-Specific Effects of Medium-Chain Fatty Acids

Diabetes and Obesity Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
Diabetes (Impact Factor: 8.1). 08/2009; 58(11):2547-54. DOI: 10.2337/db09-0784
Source: PubMed


Medium-chain fatty acids (MCFAs) have been reported to be less obesogenic than long-chain fatty acids (LCFAs); however, relatively little is known regarding their effect on insulin action. Here, we examined the tissue-specific effects of MCFAs on lipid metabolism and insulin action.
C57BL6/J mice and Wistar rats were fed either a low-fat control diet or high-fat diets rich in MCFAs or LCFAs for 4-5 weeks, and markers of mitochondrial oxidative capacity, lipid levels, and insulin action were measured.
Mice fed the MCFA diet displayed reduced adiposity and better glucose tolerance than LCFA-fed animals. In skeletal muscle, triglyceride levels were increased by the LCFA diet (77%, P < 0.01) but remained at low-fat diet control levels in the MCFA-fed animals. The LCFA diet increased (20-50%, P < 0.05) markers of mitochondrial metabolism in muscle compared with low-fat diet-fed controls; however; the increase in oxidative capacity was substantially greater in MCFA-fed animals (50-140% versus low-fat-fed controls, P < 0.01). The MCFA diet induced a greater accumulation of liver triglycerides than the LCFA diet, likely due to an upregulation of several lipogenic enzymes. In rats, isocaloric feeding of MCFA or LCFA high-fat diets induced hepatic insulin resistance to a similar degree; however, insulin action was preserved at the level of low-fat diet-fed controls in muscle and adipose from MCFA-fed animals.
MCFAs reduce adiposity and preserve insulin action in muscle and adipose, despite inducing steatosis and insulin resistance in the liver. Dietary supplementation with MCFAs may therefore be beneficial for preventing obesity and peripheral insulin resistance.

Download full-text


Available from: Ji-Ming Ye
  • Source
    • "Equal amounts of samples were resolved by SDS-PAGE and transferred to PVDF membranes. The membranes were then cut into 4 or 5 individual strips for immunoblotting of specific proteins using procedures and antibodies described previously81653. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Excess dietary lipid generally leads to fat deposition and impaired glucose homeostasis, but consumption of fish oil (FO) alleviates many of these detrimental effects. The beneficial effects of FO are thought to be mediated largely via activation of the nuclear receptor peroxisomal-proliferator-activated receptor α (PPARα) by omega-3 polyunsaturated fatty acids and the resulting upregulation of lipid catabolism. However, pharmacological and genetic PPARα manipulations have yielded variable results. We have compared the metabolic effects of FO supplementation and the synthetic PPARα agonist Wy-14,643 (WY) in mice fed a lard-based high-fat diet. In contrast to FO, WY treatment resulted in little protection against diet-induced obesity and glucose intolerance, despite upregulating many lipid metabolic pathways. These differences were likely due to differential effects on hepatic lipid synthesis, with FO decreasing and WY amplifying hepatic lipid accumulation. Our results highlight that the beneficial metabolic effects of FO are likely mediated through multiple independent pathways.
    Full-text · Article · Jul 2014 · Scientific Reports
  • Source
    • "It is clear that the majority of MCFAs are efficiently used for energy production by mitochondrial b-oxidation after portal transport to the liver (Wojtczak and Schönfeld, 1993; Turner et al., 2009). Most of the absorbed MCFAs are bound to serum albumin with a high affinity and capacity during direct transport to the liver in portal blood (Ashbrook et al., 1972; Kenyon and Hamilton, 1994). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Medium-chain fatty acids (MCFAs) are found at higher levels in milk lipids of many animal species and in the oil fraction of several plants, including coconuts, palm kernels and certain Cuphea species. Medium-chain triglycerides (MCTs) and fatty acids are efficiently absorbed and metabolized and are therefore used for piglet nutrition. They may provide instant energy and also have physiological benefits beyond their energetic value contributing to several findings of improved performance in piglet-feeding trials. MCTs are effectively hydrolyzed by gastric and pancreatic lipases in the newborn and suckling young, allowing rapid provision of energy for both enterocytes and intermediary hepatic metabolism. MCFAs affect the composition of the intestinal microbiota and have inhibitory effects on bacterial concentrations in the digesta, mainly on Salmonella and coliforms. However, most studies have been performed in vitro up to now and in vivo data in pigs are still scarce. Effects on the gut-associated and general immune function have been described in several animal species, but they have been less studied in pigs. The addition of up to 8% of a non-esterified MCFA mixture in feed has been described, but due to the sensory properties this can have a negative impact on feed intake. This may be overcome by using MCTs, allowing dietary inclusion rates up to 15%. Feeding sows with diets containing 15% MCTs resulted in a lower mortality of newborns and better development, particularly of underweight piglets. In conclusion, MCFAs and MCTs offer advantages for the improvement of energy supply and performance of piglets and may stabilize the intestinal microbiota, expanding the spectrum of feed additives supporting piglet health in the post-weaning period.
    Full-text · Article · Jun 2011 · Animal Health Research Reviews
  • [Show abstract] [Hide abstract]
    ABSTRACT: Signal sets are considered which give rise to multitone M -ary frequency shift keying (MT-MFSK) modulation, which represents a bandwidth efficient alternative to optimum performance modulation schemes for the AWGN channel (simplex signaling for coherent detection and orthogonal signaling for noncoherent detection). The channel is examined in the power-limited region, and it is shown that MT-MFSK modulation exhibits optimum asymptotic performance with bandwidth efficiency gains of an order of magnitude over the orthogonal MFSK modulation technique for sets of finite size. MT-MFSK is viewed as a class of signal sets derived from combinatorial designs. The main properties and structure of such sets are presented and exploited to derive tight upper bounds for the error probability
    No preview · Conference Paper · Jun 1990
Show more