Abstract
BackgroundObesity is associated with an impaired ability to switch from fatty acid to glucose oxidation during the fasted to fed transition, particularly in skeletal muscle. However, whether such metabolic inflexibility is reflected at the gene transcription level in circulatory mononuclear cells (MNC) is not known.MethodsThe whole-body respiratory quotient (RQ) and transcriptional regulation of genes involved in carbohydrate and lipid metabolism in MNC were measured during fasting and in response (up to 6 h) to high-carbohydrate and high-fat meals in nine lean insulin-sensitive and nine obese insulin-resistant men.ResultsCompared to lean subjects, obese subjects had an impaired ability to increase RQ and switch from fatty acid to glucose oxidation following the high-carbohydrate meal (interaction term P < 0.05). This was accompanied by an impaired induction of genes involved in oxidative metabolism of glucose in MNC, such as phosphofructokinase (PFK), pyruvate dehydrogenase kinase 4 (PDK4), peroxisome proliferator-activated receptor alpha (PPARα) and uncoupling protein 3 (UCP3) and increased expression of genes involved in fatty acid metabolism, such as fatty acid translocase (FAT/CD36) and fatty acid synthase (FASN) (P < 0.05). On the contrary, there were no differences in the gene expression profiles between lean and obese subjects following the high-fat meal.ConclusionsPostprandial expression profiles of genes involved in glucose and fatty acid metabolism in the MNC reflect the differing metabolic flexibility phenotypes of our cohort of lean and obese individuals. These differences in metabolic flexibility between the lean and obese are elicited by an acute meal challenge that is rich in carbohydrate but not fat.Electronic supplementary materialThe online version of this article (doi:10.1186/s12986-016-0135-5) contains supplementary material, which is available to authorized users.
Highlights
Obesity is associated with an impaired ability to switch from fatty acid to glucose oxidation during the fasted to fed transition, in skeletal muscle
We examined the transcriptional responses of genes involved in glycolytic, oxidative and fatty acid metabolism in mononuclear cells (MNC) in response to a single high-carbohydrate or high-fat meal among individuals with different metabolic flexibility
The fasting expression levels of all genes examined, except pyruvate dehydrogenase kinase 4 (PDK4), trended lower in obese compared to lean subjects but reached statistical significance only for HK, PFK, PPARα, fatty acid synthase (FASN), and stearoyl Co-A desaturase (SCD) (Additional file 3: Figure S1)
Summary
Obesity is associated with an impaired ability to switch from fatty acid to glucose oxidation during the fasted to fed transition, in skeletal muscle. Whether such metabolic inflexibility is reflected at the gene transcription level in circulatory mononuclear cells (MNC) is not known. Normal energy metabolism is characterized by periodic shifts between glucose and fatty acid oxidation according to physiological and nutritional status [1, 2] Impaired ability for such a switch in fuel oxidation, known as metabolic inflexibility, has been shown to occur early in the pathogenesis of insulin resistance, and is closely associated with obesity [3,4,5]. MNCs have been suggested as an alternative to muscle biopsies to study mitochondrial dysfunction [20, 21]
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