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...