Abstract
Obesity-related conditions including heart disease, stroke, and type 2 diabetes are leading causes of preventable death. Recent evidence suggests that altered myocellular lipid metabolism in obesity may lead to increased insulin resistance (IR) that predisposes to these disorders. To test the hypothesis that muscles rich in type I vs. type II muscle fibers would exhibit similar changes in intramyocellular lipid (IMCL) and extramyocellular lipid (EMCL) content in obesity, we utilized a new four-dimensional multi echo echo-planar correlated spectroscopic imaging technique that allows separate determination of IMCL and EMCL content in individual calf muscles in obese vs. normal healthy human subjects. Calf muscles were scanned in 32 obese and 11 healthy subjects using a 3T MRI/MRS scanner, and IR in the obese subjects was documented by glucose tolerance testing. In obese subjects, elevation of both IMCL and EMCL content was observed in the gastrocnemius and tibialis anterior muscles (with mixed type I and II fiber content), while a significant increase in only IMCL content (+48%, p < 0.001) was observed in the soleus muscle (predominantly type I fibers). These observations indicate unexpected differences in changes in myolipid metabolism in type I vs. type II rich muscle regions in obesity, perhaps related to IR, and warrant further investigation.
Highlights
Increased intramyocellular lipid (IMCL) and extramyocellular lipid (EMCL) were observed in all three highlighted muscle locations
A significant increase in both IMCL/Cr and EML/Cr was observed in the gastrocnemius and there was a non-significant trend toward an increase in both IMCL/Cr and EMCL/Cr in the tibialis anterior
Previous histologic studies have shown that the soleus is the calf muscle compartment with the highest proportion of type I muscle fibers, with type I fiber content being significantly lower in the gastrocnemius
Summary
The measurement of IMCL by 1H -MRS has become of interest in the study of altered lipid metabolism in human skeletal muscle[6,7,9,10,11,12,13,14], since it has been reported that IMCL is negatively correlated with insulin sensitivity in sedentary and diabetic volunteers[15,16]. To investigate the potential utility of the MRSI technique in assessing obesity-related metabolite parameters in muscle, and begin to more accurately define changes in IMCL and EMCL in obesity, we used the recently implemented four dimensional (4D) multi-echo echo planar correlated spectroscopic imaging (ME-EPCOSI) technique[30] to quantify lipids and metabolites in the soleus, tibialis anterior and gastrocnemius of calf muscles of obese and normal healthy subjects. In a subset of the obese subjects, we evaluated the association between the above measurements and insulin sensitivity
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