Metabolic gene expression profile in circulating mononuclear cells reflects obesity-associated metabolic inflexibility
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Metabolic gene expression profile in circulating mononuclear cells reflects obesity-associated metabolic inflexibility. / Baig, Sonia; Parvaresh Rizi, Ehsan; Shabeer, Muhammad; Chhay, Vanna; Mok, Shao Feng; Loh, Tze Ping; Magkos, Faidon; Vidal-Puig, Antonio; Tai, E Shyong; Khoo, Chin Meng; Toh, Sue-Anne.
In: Nutrition & Metabolism, Vol. 13, 74, 2016.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Metabolic gene expression profile in circulating mononuclear cells reflects obesity-associated metabolic inflexibility
AU - Baig, Sonia
AU - Parvaresh Rizi, Ehsan
AU - Shabeer, Muhammad
AU - Chhay, Vanna
AU - Mok, Shao Feng
AU - Loh, Tze Ping
AU - Magkos, Faidon
AU - Vidal-Puig, Antonio
AU - Tai, E Shyong
AU - Khoo, Chin Meng
AU - Toh, Sue-Anne
N1 - (Ekstern)
PY - 2016
Y1 - 2016
N2 - 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 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.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.
AB - 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 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.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.
KW - Faculty of Science
KW - Mononuclear cells
KW - Metabolic flexibility
KW - Gene expression
KW - Macronutrients
KW - Obesity
U2 - 10.1186/s12986-016-0135-5
DO - 10.1186/s12986-016-0135-5
M3 - Journal article
C2 - 27800008
VL - 13
JO - Nutrition & Metabolism
JF - Nutrition & Metabolism
SN - 1743-7075
M1 - 74
ER -
ID: 289959869