Serum levels of RBP4 and adipose tissue levels of PTP1B are increased in obese men resident in northeast Scotland without associated changes in ER stress response genes

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Abstract

Background: Retinol-binding protein 4 (RBP4) is an adipokine identified as a marker of insulin resistance in mice and humans. Protein tyrosine phosphatase 1B (PTP1B) expression levels, as well as other genes involved in the endoplasmic-reticulum (ER) stress response, are increased in adipose tissue of obese, high-fat diet fed mice. In this study, we investigated if serum- and/or adipose-tissue RBP4 protein levels, and expression levels of PTP1B and other ER stress-response genes, are altered in obese and obese/diabetic men resident in North East of Scotland.
Methods: We studied three groups of male volunteers: 1) normal/overweight (body mass index (BMI) <30), 2) obese (BMI>30) and 3) obese/diabetic group (BMI>30) controlling their diabetes either by diet or anti-diabetic drug, metformin. We analysed their serum- and adipose-tissue RBP4 protein levels, as well as adipose tissue mRNA expression of PTP1B, BIP (binding immunoglobulinprotein), ATF4 (activated transcription factor 4) and GRP94 (glucose-regulated protein 94), alongside other markers of adiposity (% body fat, leptin, cholesterol, triglycerides) and insulin resistance (oral glucose tolerance tests (OGTT), insulin, HOMA-IR, C-reactive protein (CRP), adiponectin).
Results: We found that obese Scottish subjects had significantly higher serum-RBP4 protein levels in comparison to the normal/overweight subjects (p<0.01). Serum-RBP4 levels were normalized in obese/diabetic subjects treated with diet or metformin (p<0.05). Adipose-tissue RBP4 protein levels were comparable between all three groups of subjects and so were serum- and adipose-transthyretin (TTR) levels. Adipose-tissue PTP1B mRNA levels were increased in obese subjects in comparison to normal/overweight subjects (p<0.05), however diet and/or metformin treatment did not reverse this effect. Adipose-tissue BIP, ATF4 and GRP94 expression levels were unchanged in obese and obese/diabetic subjects.
Conclusions: Human obesity results in an increase in serum, but not adipose-tissue, RBP4 protein levels and these are normalized in obese/diabetic subjects, which exhibit improvements in insulin sensitivity through diet or metformin treatment. However, whilst adipose-tissue PTP1B mRNA levels do increase in obese Scottish subjects, these remain high in obese/diabetics on diet or metformin treatment.
Original languageEnglish
Pages (from-to)403-411
Number of pages9
JournalInternational Journal of General Medicine
Volume5
DOIs
Publication statusPublished - May 2012

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Non-Receptor Type 1 Protein Tyrosine Phosphatase
Retinol-Binding Proteins
Endoplasmic Reticulum Stress
Scotland
Adipose Tissue
Metformin
Serum
Genes
Diet
Insulin Resistance
Proteins
Messenger RNA
Body Mass Index
Transcription Factors
Diabetic Diet
Prealbumin
Adipokines
Adiponectin
Adiposity
High Fat Diet

Cite this

@article{dcbf5991e8824fdaa0646bd62f3dcbb5,
title = "Serum levels of RBP4 and adipose tissue levels of PTP1B are increased in obese men resident in northeast Scotland without associated changes in ER stress response genes",
abstract = "Background: Retinol-binding protein 4 (RBP4) is an adipokine identified as a marker of insulin resistance in mice and humans. Protein tyrosine phosphatase 1B (PTP1B) expression levels, as well as other genes involved in the endoplasmic-reticulum (ER) stress response, are increased in adipose tissue of obese, high-fat diet fed mice. In this study, we investigated if serum- and/or adipose-tissue RBP4 protein levels, and expression levels of PTP1B and other ER stress-response genes, are altered in obese and obese/diabetic men resident in North East of Scotland. Methods: We studied three groups of male volunteers: 1) normal/overweight (body mass index (BMI) <30), 2) obese (BMI>30) and 3) obese/diabetic group (BMI>30) controlling their diabetes either by diet or anti-diabetic drug, metformin. We analysed their serum- and adipose-tissue RBP4 protein levels, as well as adipose tissue mRNA expression of PTP1B, BIP (binding immunoglobulinprotein), ATF4 (activated transcription factor 4) and GRP94 (glucose-regulated protein 94), alongside other markers of adiposity ({\%} body fat, leptin, cholesterol, triglycerides) and insulin resistance (oral glucose tolerance tests (OGTT), insulin, HOMA-IR, C-reactive protein (CRP), adiponectin). Results: We found that obese Scottish subjects had significantly higher serum-RBP4 protein levels in comparison to the normal/overweight subjects (p<0.01). Serum-RBP4 levels were normalized in obese/diabetic subjects treated with diet or metformin (p<0.05). Adipose-tissue RBP4 protein levels were comparable between all three groups of subjects and so were serum- and adipose-transthyretin (TTR) levels. Adipose-tissue PTP1B mRNA levels were increased in obese subjects in comparison to normal/overweight subjects (p<0.05), however diet and/or metformin treatment did not reverse this effect. Adipose-tissue BIP, ATF4 and GRP94 expression levels were unchanged in obese and obese/diabetic subjects. Conclusions: Human obesity results in an increase in serum, but not adipose-tissue, RBP4 protein levels and these are normalized in obese/diabetic subjects, which exhibit improvements in insulin sensitivity through diet or metformin treatment. However, whilst adipose-tissue PTP1B mRNA levels do increase in obese Scottish subjects, these remain high in obese/diabetics on diet or metformin treatment.",
author = "Nigel Hoggard and Abdelali Agouni and Nimesh Mody and Mirela Delibegovic",
year = "2012",
month = "5",
doi = "10.2147/IJGM.S25879",
language = "English",
volume = "5",
pages = "403--411",
journal = "International Journal of General Medicine",
issn = "1178-7074",
publisher = "Dove Medical Press Ltd.",

}

TY - JOUR

T1 - Serum levels of RBP4 and adipose tissue levels of PTP1B are increased in obese men resident in northeast Scotland without associated changes in ER stress response genes

AU - Hoggard, Nigel

AU - Agouni, Abdelali

AU - Mody, Nimesh

AU - Delibegovic, Mirela

PY - 2012/5

Y1 - 2012/5

N2 - Background: Retinol-binding protein 4 (RBP4) is an adipokine identified as a marker of insulin resistance in mice and humans. Protein tyrosine phosphatase 1B (PTP1B) expression levels, as well as other genes involved in the endoplasmic-reticulum (ER) stress response, are increased in adipose tissue of obese, high-fat diet fed mice. In this study, we investigated if serum- and/or adipose-tissue RBP4 protein levels, and expression levels of PTP1B and other ER stress-response genes, are altered in obese and obese/diabetic men resident in North East of Scotland. Methods: We studied three groups of male volunteers: 1) normal/overweight (body mass index (BMI) <30), 2) obese (BMI>30) and 3) obese/diabetic group (BMI>30) controlling their diabetes either by diet or anti-diabetic drug, metformin. We analysed their serum- and adipose-tissue RBP4 protein levels, as well as adipose tissue mRNA expression of PTP1B, BIP (binding immunoglobulinprotein), ATF4 (activated transcription factor 4) and GRP94 (glucose-regulated protein 94), alongside other markers of adiposity (% body fat, leptin, cholesterol, triglycerides) and insulin resistance (oral glucose tolerance tests (OGTT), insulin, HOMA-IR, C-reactive protein (CRP), adiponectin). Results: We found that obese Scottish subjects had significantly higher serum-RBP4 protein levels in comparison to the normal/overweight subjects (p<0.01). Serum-RBP4 levels were normalized in obese/diabetic subjects treated with diet or metformin (p<0.05). Adipose-tissue RBP4 protein levels were comparable between all three groups of subjects and so were serum- and adipose-transthyretin (TTR) levels. Adipose-tissue PTP1B mRNA levels were increased in obese subjects in comparison to normal/overweight subjects (p<0.05), however diet and/or metformin treatment did not reverse this effect. Adipose-tissue BIP, ATF4 and GRP94 expression levels were unchanged in obese and obese/diabetic subjects. Conclusions: Human obesity results in an increase in serum, but not adipose-tissue, RBP4 protein levels and these are normalized in obese/diabetic subjects, which exhibit improvements in insulin sensitivity through diet or metformin treatment. However, whilst adipose-tissue PTP1B mRNA levels do increase in obese Scottish subjects, these remain high in obese/diabetics on diet or metformin treatment.

AB - Background: Retinol-binding protein 4 (RBP4) is an adipokine identified as a marker of insulin resistance in mice and humans. Protein tyrosine phosphatase 1B (PTP1B) expression levels, as well as other genes involved in the endoplasmic-reticulum (ER) stress response, are increased in adipose tissue of obese, high-fat diet fed mice. In this study, we investigated if serum- and/or adipose-tissue RBP4 protein levels, and expression levels of PTP1B and other ER stress-response genes, are altered in obese and obese/diabetic men resident in North East of Scotland. Methods: We studied three groups of male volunteers: 1) normal/overweight (body mass index (BMI) <30), 2) obese (BMI>30) and 3) obese/diabetic group (BMI>30) controlling their diabetes either by diet or anti-diabetic drug, metformin. We analysed their serum- and adipose-tissue RBP4 protein levels, as well as adipose tissue mRNA expression of PTP1B, BIP (binding immunoglobulinprotein), ATF4 (activated transcription factor 4) and GRP94 (glucose-regulated protein 94), alongside other markers of adiposity (% body fat, leptin, cholesterol, triglycerides) and insulin resistance (oral glucose tolerance tests (OGTT), insulin, HOMA-IR, C-reactive protein (CRP), adiponectin). Results: We found that obese Scottish subjects had significantly higher serum-RBP4 protein levels in comparison to the normal/overweight subjects (p<0.01). Serum-RBP4 levels were normalized in obese/diabetic subjects treated with diet or metformin (p<0.05). Adipose-tissue RBP4 protein levels were comparable between all three groups of subjects and so were serum- and adipose-transthyretin (TTR) levels. Adipose-tissue PTP1B mRNA levels were increased in obese subjects in comparison to normal/overweight subjects (p<0.05), however diet and/or metformin treatment did not reverse this effect. Adipose-tissue BIP, ATF4 and GRP94 expression levels were unchanged in obese and obese/diabetic subjects. Conclusions: Human obesity results in an increase in serum, but not adipose-tissue, RBP4 protein levels and these are normalized in obese/diabetic subjects, which exhibit improvements in insulin sensitivity through diet or metformin treatment. However, whilst adipose-tissue PTP1B mRNA levels do increase in obese Scottish subjects, these remain high in obese/diabetics on diet or metformin treatment.

U2 - 10.2147/IJGM.S25879

DO - 10.2147/IJGM.S25879

M3 - Article

VL - 5

SP - 403

EP - 411

JO - International Journal of General Medicine

JF - International Journal of General Medicine

SN - 1178-7074

ER -