In:
American Journal of Physiology-Endocrinology and Metabolism, American Physiological Society, Vol. 301, No. 1 ( 2011-07), p. E105-E112
Abstract:
An impaired ability to store fatty acids (FA) in subcutaneous adipose tissue (SAT) may be implicated in the pathogenesis of obesity-related diseases via overexposure of lean tissues and production of free radicals from FA oxidation (FAO). We studied regional FA metabolism in skeletal muscle and adipose tissue in humans and investigated the long-term effects of the FAO inhibitor trimetazidine on glucose and FA metabolism. Positron emission tomography (PET) and [ 11 C]palmitate were used to compare FA metabolism in SAT and skeletal muscle between eight obese and eight nonobese subjects (BMI ≥/ 〈 30 kg/m 2 ). A subgroup of nine subjects underwent a 1-mo trimetazidine administration. PET with [ 11 C]palmitate and [ 18 F]fluorodeoxyglucose, indirect calorimetry, and MRI before and after this period were performed to characterize glucose and FA metabolism, fat masses, skeletal muscle triglyceride, and creatine contents. Obesity was characterized by a 100% elevation in FAO and a defect in the FA esterification rate constant ( P 〈 0.05) in skeletal muscle. FA esterification was reduced by ∼70% in SAT ( P 〈 0.001) in obese vs. control subjects. The degrees of obesity and insulin resistance were both negatively associated with esterification-related parameters and positively with FAO ( P 〈 0.05). Trimetazidine increased skeletal muscle FA esterification ( P 〈 0.01) and mildly upregulated glucose phosphorylation ( P = 0.066). Our data suggest that human obesity is characterized by a defect in tissue FA storage capability, which is accompanied by a (potentially compensatory) elevation in skeletal muscle FAO; trimetazidine diverted FA from oxidative to nonoxidative pathways and provoked an initial activation of glucose metabolism in skeletal muscle.
Type of Medium:
Online Resource
ISSN:
0193-1849
,
1522-1555
DOI:
10.1152/ajpendo.00680.2010
Language:
English
Publisher:
American Physiological Society
Publication Date:
2011
detail.hit.zdb_id:
1477331-4
SSG:
12
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