Muscle
lipid overload and the associated accumulation of
lipid intermediates play an important role in the development of
insulin resistance.
Carnitine insufficiency is a common feature of
insulin-resistant states and might lead to incomplete
fatty acid oxidation and impaired export of
lipid intermediates out of the mitochondria. The aim of the present study was to test the hypothesis that
carnitine supplementation reduces high-fat diet-induced lipotoxicity, improves muscle mitochondrial function, and ameliorates
insulin resistance. Wistar rats were fed either normal chow or a high-fat diet for 15 wk. One group of high-fat diet-fed rats was supplemented with 300 mg·kg(-1)·day(-1)
L-carnitine during the last 8 wk. Muscle mitochondrial function was measured in vivo by (31)P magnetic resonance spectroscopy (MRS) and ex vivo by high-resolution respirometry. Muscle
lipid status was determined by (1)H MRS (intramyocellular
lipids) and tandem mass spectrometry (acylcarnitines). High-fat diet feeding induced
insulin resistance and was associated with decreases in muscle and blood free
carnitine, elevated levels of muscle
lipids and acylcarnitines, and an increased number of muscle mitochondria that showed an improved capacity to oxidize fat-derived substrates when tested ex vivo. This was, however, not accompanied by an increase in muscle oxidative capacity in vivo, indicating that in vivo mitochondrial function was compromised. Despite partial normalization of muscle and blood free
carnitine content,
carnitine supplementation did not induce improvements in muscle
lipid status, in vivo mitochondrial function, or
insulin sensitivity.
Carnitine insufficiency, therefore, does not play a major role in high-fat diet-induced muscle
mitochondrial dysfunction in vivo.