Genes involved in oxidative stress pathways are differentially expressed in circulating mononuclear cells derived from obese insulin-resistant and lean insulin-sensitive individuals following a single mixed-meal challenge

Sonia Baig; Ehsan Parvaresh Rizi; Chelsea Chia; Muhammad Shabeer; Nweni Aung; Tze Ping Loh; Faidon Magkos; Antonio Vidal-Puig; Raymond C S Seet; Chin Meng Khoo; Sue-Anne Toh

doi:10.3389/fendo.2019.00256

Genes involved in oxidative stress pathways are differentially expressed in circulating mononuclear cells derived from obese insulin-resistant and lean insulin-sensitive individuals following a single mixed-meal challenge

Sonia Baig, Ehsan Parvaresh Rizi, Chelsea Chia, Muhammad Shabeer, Nweni Aung, Tze Ping Loh, Faidon Magkos, Antonio Vidal-Puig, Raymond C S Seet, Chin Meng Khoo, Sue-Anne Toh

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Abstract

Background: Oxidative stress induced by nutritional overload has been linked to the pathogenesis of insulin resistance, which is associated with metabolic syndrome, obesity, type 2 diabetes and diabetic vascular complications. Postprandial changes in expression of oxidative stress pathway genes in obese vs. lean individuals, following intake of different types of meals varying in macronutrient composition have not been characterized to date. Here we aimed to test whether/how oxidative stress responses in obese vs. lean individuals are modulated by meal composition. Methods: High-carbohydrate (HC), high-fat (HF), or high-protein (HP) liquid mixed meals were administered to study subjects (lean insulin-sensitive, n = 9 and obese insulin-resistant, n = 9). Plasma levels of glucose and insulin, lipid profile, urinary F2-isoprostanes (F2-IsoP), and expression levels of genes of oxidative stress pathways were assessed in mononuclear cells (MNC) derived from fresh peripheral blood, at baseline and up to 6-h postprandial states. Differences in these parameters were compared between insulin-sensitive/resistant groups undergoing aforementioned meal challenges. Results: Obese individuals exhibited increased pro-oxidant (i.e., CYBB and CYBA) and anti-oxidant (i.e., TXN RD1) gene expression in the postprandial state, compared with lean subjects, regardless of meal type (P interaction for group × time < 0.05). By contrast, lean subjects had higher expression of NCF-4 gene (pro-oxidant) after HC meal and SOD1 gene (anti-oxidant) after HC and HF meals (P interaction for group × meal < 0.05). There was an increase in postprandial level of urinary F2-IsoP in the obese (P < 0.05) but not lean group. Conclusions: These findings may represent an adaptive oxidative response to mitigate increased stress induced by acute nutritional excess. Further, the results suggest an increased predisposition of obese subjects to oxidative stress. Chronic nutritional excess resulting in increases in body weight and adiposity might lead to decompensation leading to worsening insulin resistance and its sequel. Insights from this study could impact on nutritional recommendations for obese subjects at high-risk of cardiovascular diseases.

Original language	English
Article number	256
Journal	Frontiers in Endocrinology
Volume	10
Number of pages	9
ISSN	1664-2392
DOIs	https://doi.org/10.3389/fendo.2019.00256
Publication status	Published - 2019
Externally published	Yes

Keywords

Faculty of Science
Obesity
Mononuclear cells
Oxidative stress
Gene expression
Macronutrients

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Baig, S., Parvaresh Rizi, E., Chia, C., Shabeer, M., Aung, N., Loh, T. P., Magkos, F., Vidal-Puig, A., Seet, R. C. S., Khoo, C. M., & Toh, S.-A. (2019). Genes involved in oxidative stress pathways are differentially expressed in circulating mononuclear cells derived from obese insulin-resistant and lean insulin-sensitive individuals following a single mixed-meal challenge. Frontiers in Endocrinology, 10, Article 256. https://doi.org/10.3389/fendo.2019.00256

Genes involved in oxidative stress pathways are differentially expressed in circulating mononuclear cells derived from obese insulin-resistant and lean insulin-sensitive individuals following a single mixed-meal challenge. / Baig, Sonia; Parvaresh Rizi, Ehsan; Chia, Chelsea et al.
In: Frontiers in Endocrinology, Vol. 10, 256, 2019.

Research output: Contribution to journal › Journal article › Research › peer-review

Baig, S, Parvaresh Rizi, E, Chia, C, Shabeer, M, Aung, N, Loh, TP, Magkos, F, Vidal-Puig, A, Seet, RCS, Khoo, CM & Toh, S-A 2019, 'Genes involved in oxidative stress pathways are differentially expressed in circulating mononuclear cells derived from obese insulin-resistant and lean insulin-sensitive individuals following a single mixed-meal challenge', Frontiers in Endocrinology, vol. 10, 256. https://doi.org/10.3389/fendo.2019.00256

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title = "Genes involved in oxidative stress pathways are differentially expressed in circulating mononuclear cells derived from obese insulin-resistant and lean insulin-sensitive individuals following a single mixed-meal challenge",

abstract = "Background: Oxidative stress induced by nutritional overload has been linked to the pathogenesis of insulin resistance, which is associated with metabolic syndrome, obesity, type 2 diabetes and diabetic vascular complications. Postprandial changes in expression of oxidative stress pathway genes in obese vs. lean individuals, following intake of different types of meals varying in macronutrient composition have not been characterized to date. Here we aimed to test whether/how oxidative stress responses in obese vs. lean individuals are modulated by meal composition. Methods: High-carbohydrate (HC), high-fat (HF), or high-protein (HP) liquid mixed meals were administered to study subjects (lean insulin-sensitive, n = 9 and obese insulin-resistant, n = 9). Plasma levels of glucose and insulin, lipid profile, urinary F2-isoprostanes (F2-IsoP), and expression levels of genes of oxidative stress pathways were assessed in mononuclear cells (MNC) derived from fresh peripheral blood, at baseline and up to 6-h postprandial states. Differences in these parameters were compared between insulin-sensitive/resistant groups undergoing aforementioned meal challenges. Results: Obese individuals exhibited increased pro-oxidant (i.e., CYBB and CYBA) and anti-oxidant (i.e., TXN RD1) gene expression in the postprandial state, compared with lean subjects, regardless of meal type (P interaction for group × time < 0.05). By contrast, lean subjects had higher expression of NCF-4 gene (pro-oxidant) after HC meal and SOD1 gene (anti-oxidant) after HC and HF meals (P interaction for group × meal < 0.05). There was an increase in postprandial level of urinary F2-IsoP in the obese (P < 0.05) but not lean group. Conclusions: These findings may represent an adaptive oxidative response to mitigate increased stress induced by acute nutritional excess. Further, the results suggest an increased predisposition of obese subjects to oxidative stress. Chronic nutritional excess resulting in increases in body weight and adiposity might lead to decompensation leading to worsening insulin resistance and its sequel. Insights from this study could impact on nutritional recommendations for obese subjects at high-risk of cardiovascular diseases.",

keywords = "Faculty of Science, Obesity, Mononuclear cells, Oxidative stress, Gene expression, Macronutrients",

author = "Sonia Baig and {Parvaresh Rizi}, Ehsan and Chelsea Chia and Muhammad Shabeer and Nweni Aung and Loh, {Tze Ping} and Faidon Magkos and Antonio Vidal-Puig and Seet, {Raymond C S} and Khoo, {Chin Meng} and Sue-Anne Toh",

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TY - JOUR

T1 - Genes involved in oxidative stress pathways are differentially expressed in circulating mononuclear cells derived from obese insulin-resistant and lean insulin-sensitive individuals following a single mixed-meal challenge

AU - Baig, Sonia

AU - Parvaresh Rizi, Ehsan

AU - Chia, Chelsea

AU - Shabeer, Muhammad

AU - Aung, Nweni

AU - Loh, Tze Ping

AU - Magkos, Faidon

AU - Vidal-Puig, Antonio

AU - Seet, Raymond C S

AU - Khoo, Chin Meng

AU - Toh, Sue-Anne

N1 - (Ekstern)

PY - 2019

Y1 - 2019

N2 - Background: Oxidative stress induced by nutritional overload has been linked to the pathogenesis of insulin resistance, which is associated with metabolic syndrome, obesity, type 2 diabetes and diabetic vascular complications. Postprandial changes in expression of oxidative stress pathway genes in obese vs. lean individuals, following intake of different types of meals varying in macronutrient composition have not been characterized to date. Here we aimed to test whether/how oxidative stress responses in obese vs. lean individuals are modulated by meal composition. Methods: High-carbohydrate (HC), high-fat (HF), or high-protein (HP) liquid mixed meals were administered to study subjects (lean insulin-sensitive, n = 9 and obese insulin-resistant, n = 9). Plasma levels of glucose and insulin, lipid profile, urinary F2-isoprostanes (F2-IsoP), and expression levels of genes of oxidative stress pathways were assessed in mononuclear cells (MNC) derived from fresh peripheral blood, at baseline and up to 6-h postprandial states. Differences in these parameters were compared between insulin-sensitive/resistant groups undergoing aforementioned meal challenges. Results: Obese individuals exhibited increased pro-oxidant (i.e., CYBB and CYBA) and anti-oxidant (i.e., TXN RD1) gene expression in the postprandial state, compared with lean subjects, regardless of meal type (P interaction for group × time < 0.05). By contrast, lean subjects had higher expression of NCF-4 gene (pro-oxidant) after HC meal and SOD1 gene (anti-oxidant) after HC and HF meals (P interaction for group × meal < 0.05). There was an increase in postprandial level of urinary F2-IsoP in the obese (P < 0.05) but not lean group. Conclusions: These findings may represent an adaptive oxidative response to mitigate increased stress induced by acute nutritional excess. Further, the results suggest an increased predisposition of obese subjects to oxidative stress. Chronic nutritional excess resulting in increases in body weight and adiposity might lead to decompensation leading to worsening insulin resistance and its sequel. Insights from this study could impact on nutritional recommendations for obese subjects at high-risk of cardiovascular diseases.

AB - Background: Oxidative stress induced by nutritional overload has been linked to the pathogenesis of insulin resistance, which is associated with metabolic syndrome, obesity, type 2 diabetes and diabetic vascular complications. Postprandial changes in expression of oxidative stress pathway genes in obese vs. lean individuals, following intake of different types of meals varying in macronutrient composition have not been characterized to date. Here we aimed to test whether/how oxidative stress responses in obese vs. lean individuals are modulated by meal composition. Methods: High-carbohydrate (HC), high-fat (HF), or high-protein (HP) liquid mixed meals were administered to study subjects (lean insulin-sensitive, n = 9 and obese insulin-resistant, n = 9). Plasma levels of glucose and insulin, lipid profile, urinary F2-isoprostanes (F2-IsoP), and expression levels of genes of oxidative stress pathways were assessed in mononuclear cells (MNC) derived from fresh peripheral blood, at baseline and up to 6-h postprandial states. Differences in these parameters were compared between insulin-sensitive/resistant groups undergoing aforementioned meal challenges. Results: Obese individuals exhibited increased pro-oxidant (i.e., CYBB and CYBA) and anti-oxidant (i.e., TXN RD1) gene expression in the postprandial state, compared with lean subjects, regardless of meal type (P interaction for group × time < 0.05). By contrast, lean subjects had higher expression of NCF-4 gene (pro-oxidant) after HC meal and SOD1 gene (anti-oxidant) after HC and HF meals (P interaction for group × meal < 0.05). There was an increase in postprandial level of urinary F2-IsoP in the obese (P < 0.05) but not lean group. Conclusions: These findings may represent an adaptive oxidative response to mitigate increased stress induced by acute nutritional excess. Further, the results suggest an increased predisposition of obese subjects to oxidative stress. Chronic nutritional excess resulting in increases in body weight and adiposity might lead to decompensation leading to worsening insulin resistance and its sequel. Insights from this study could impact on nutritional recommendations for obese subjects at high-risk of cardiovascular diseases.

KW - Faculty of Science

KW - Obesity

KW - Mononuclear cells

KW - Oxidative stress

KW - Gene expression

KW - Macronutrients

U2 - 10.3389/fendo.2019.00256

DO - 10.3389/fendo.2019.00256

M3 - Journal article

C2 - 31068904

SN - 1664-2392

VL - 10

JO - Frontiers in Endocrinology

JF - Frontiers in Endocrinology

M1 - 256

ER -