title: Metabolic gene expression profile in circulating mononuclear cells reflects obesity-associated metabolic inflexibility.
abstract: BACKGROUND
  Obesity 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.
  
  
  METHODS
  The 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.
  
  
  RESULTS
  Compared 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 termP< 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.
  
  
  CONCLUSIONS
  Postprandial 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.
authors: Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 14 Medical Drive, Singapore, 117599 Singapore.
authors: Sonia
authors: S
authors: Baig
authors: Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 14 Medical Drive, Singapore, 117599 Singapore.|Department of Medicine, National University Health System, Singapore, Singapore.
authors: Ehsan
authors: E
authors: Parvaresh Rizi
authors: Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 14 Medical Drive, Singapore, 117599 Singapore.
authors: Muhammad
authors: M
authors: Shabeer
authors: Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 14 Medical Drive, Singapore, 117599 Singapore.
authors: Vanna
authors: V
authors: Chhay
authors: Department of Medicine, National University Health System, Singapore, Singapore.
authors: Shao Feng
authors: SF
authors: Mok
authors: Department of Laboratory Medicine, National University Health System, Singapore, Singapore.
authors: Tze Ping
authors: TP
authors: Loh
authors: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.|Singapore Institute of Clinical Sciences (SICS), ASTAR, Singapore, Singapore.
authors: Faidon
authors: F
authors: Magkos
authors: University of Cambridge Metabolic Research Laboratories, Cambridge, UK.
authors: Antonio
authors: A
authors: Vidal-Puig
authors: Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 14 Medical Drive, Singapore, 117599 Singapore.|Department of Medicine, National University Health System, Singapore, Singapore.|Duke-National University of Singapore Medical School, Singapore, Singapore.
authors: E Shyong
authors: ES
authors: Tai
authors: Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 14 Medical Drive, Singapore, 117599 Singapore.|Department of Medicine, National University Health System, Singapore, Singapore.|Duke-National University of Singapore Medical School, Singapore, Singapore.
authors: Chin Meng
authors: CM
authors: Khoo
authors: Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 14 Medical Drive, Singapore, 117599 Singapore.|Department of Medicine, National University Health System, Singapore, Singapore.|Duke-National University of Singapore Medical School, Singapore, Singapore.|Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.
authors: Sue-Anne
authors: SA
authors: Toh
keywords: Gene expression; Macronutrients; Metabolic flexibility; Mononuclear cells; Obesity