Distinct patterns of fat metabolism in skeletal muscle of normal-weight, overweight, and obese humans

Abstract

Velan SS, Said N, Durst C, Frisbee S, Frisbee J, Raylman RR, Thomas MA, Rajendran VM, Spencer RG, Alway SE. Distinct patterns of fat metabolism in skeletal muscle of normal-weight, overweight, and obese humans. Am J Physiol Regul Integr Comp Physiol 295: R1060 -R1065, 2008. First published July 30, 2008 doi:10.1152/ajpregu.90367.2008The link between body weight, lipid metabolism, and health risks is poorly understood and difficult to study. Magnetic resonance spectroscopy (MRS) permits noninvasive investigation of lipid metabolism. We extended existing two-dimensional MRS techniques to permit quantification of intra-and extramyocellular lipid (IMCL and EMCL, respectively) compartments and their degree of unsaturation in human subjects and correlated these results with body mass index (BMI). Using muscle creatine for normalization, we observed a statistically significant (P Ͻ 0.01) increase in the IMCL-to-creatine ratio with BMI (n ϭ 8 subjects per group): 5.9 Ϯ 1.7 at BMI Ͻ 25, 10.9 Ϯ 1.82 at 25 Ͻ BMI Ͻ 30, and 13.1 Ϯ 0.87 at BMI Ͼ 30. Similarly, the degree of IMCL unsaturation decreased significantly (P Ͻ 0.01) with BMI: 1.51 Ϯ 0.08 at BMI Ͻ 25, 1.30 Ϯ 0.11 at 25 Ͻ BMI Ͻ 30, and 0.90 Ϯ 0.14 at BMI Ͼ 30. We conclude that important aspects of lipid metabolism can be evaluated by two-dimensional MRS and propose that degree of unsaturation measured noninvasively may serve as a biomarker for lipid metabolic defects associated with obesity. magnetic resonance spectroscopy; lipid unsaturation; intramyocellular lipid; extramyocellular lipid THE AMOUNT OF BODY FAT is a risk factor for several obesityrelated disorders. Obesity is a known risk factor for the development of insulin resistance and diabetes and is a key component of metabolic syndrome. The causal relationship between increased dyslipidemia and adiposity and impaired glucose homeostasis is unclear, although it is known that lipid oversupply to the organs primarily involved in glucose homeostasis, that is, muscle, liver, and pancreas, leads to impaired insulin function in those tissues (22).Previous studies showed that intramyocellular lipid (IMCL) is increased with obesity and in non-insulin-dependent diabetes mellitus (9,11,15). It has been suggested that increased visceral adiposity and reduced lipid oxidation might contribute to the increase in IMCL (18). Thus the ability to monitor the IMCL pool and its properties noninvasively by magnetic resonance spectroscopy (MRS) has been an important development (4, 28). The correlation between the magnitude of the IMCL pool, as determined by MRS studies, and insulin resistance, diabetes, and disorders of lipid metabolism has been previously demonstrated (2,3,32,33). Nevertheless, quantification of IMCL and extramyocellular lipid (EMCL) by MRS remains highly problematic (32). The ability to distinguish IMCL from EMCL is based on their different bulk magnetic susceptibility effects due to their geometric arrangements within muscle, which leads to a spectroscopic frequency separation between the two pools; this sepa...

Cardiac function and lipid distribution in rats fed a high-fat diet: in vivo magnetic resonance imaging and spectroscopy

“…7), obtained from the location where the MRS was performed, showed the fibers to be predominantly parallel to the magnetic field direction. The ϪCH 3 signal from total creatine (phosphocreatine and creatine) showed a triplet centered at 3.03 ppm with the splitting being due to residual dipolar coupling; this outcome has been observed from skeletal muscle that is variously orientated relative to the direction of the magnetic field (4,5,31,(42)(43)(44). This independently confirmed that the fibers were predominantly parallel to the magnetic field.…”

“…Specifically, the detection of two lipid pools in skeletal muscle with a 1 H NMR spectroscopic chemical shift difference between peaks of 0.2 parts per million (ppm) is attributed to the intra-and extramyocellular lipid (IMCL and EMCL, respectively) pools. Several groups have now established the fact that the IMCL is strongly associated with insulin resistance and diabetes in both rodents and humans (5,15,31,42,44). Recently, the presence of two lipid pools, including IMCL and EMCL, was demonstrated in cardiac muscle of patients with muscular dystrophy (34).…”

Effect of J‐coupling on lipid composition determination with localized proton magnetic resonance spectroscopy at 9.4 T

“…LIPID MEASUREMENTS by proton magnetic resonance spectroscopy (MRS) have been useful in understanding a number of disorders, including diabetes (1-3), obesity (3)(4)(5), liver disease (6,7), and cancer (3,(8)(9)(10). It has been suggested that there may be a link between the composition of fatty tissue and the risk of suffering from such diseases (11,12).…”

Investigation of adipose tissues in Zucker rats using in vivo and ex vivo magnetic resonance spectroscopy

“…A defect in accumulating unsaturated fats might be supported by a defi cit in gene expression of specifi c transporters such as CD 36 ( 38 ). It should be noted that a decrease in unsaturation with the increase of the body mass index has been also found in skeletal human muscle ( 8 ). Such a decrease was interpreted focusing on the desaturase enzymes, termed ⌬ 9 , ⌬ 6 , ⌬ 5 , and ⌬ 4 , and positing increased activity of the fi rst two and decreased activity of ⌬ 5 ( 39 ).…”

“…areas of different peaks in NMR spectra ( 8,23,24 ). Strobel et al ( 23 ) have demonstrated that reliable calculation of peak areas requires fi tting of spectral lines and correction of peak intensity by the T2 value.…”