Agouni, Abdelali

Delibegovic, Mirela

Hoggard, Nigel

Mody, Nimesh

International Journal of General Medicine

English

PubMed

Nigel Hoggard1, Abdelali Agouni2, Nimesh Mody2, Mirela Delibegovic21Rowett Institute of Nutrition and Health, 2Integrative Physiology, University of Aberdeen, Aberdeen, UKBackground: 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 northeast Scotland.Methods: We studied three groups of male volunteers: (1) normal/overweight (body mass index [BMI] &amp;lt; 30), (2) obese (BMI &amp;gt; 30), and (3) obese/diabetic (BMI &amp;gt; 30) controlling their diabetes either by diet or the antidiabetic drug metformin. We analyzed their serum and adipose tissue RBP4 protein levels as well as adipose tissue mRNA expression of PTP1B, binding immunoglobulin protein (BIP), activated transcription factor 4 (ATF4), and glucose-regulated protein 94 (GRP94) alongside other markers of adiposity (percentage body fat, leptin, cholesterol, triglycerides) and insulin resistance (oral glucose tolerance tests, insulin, homeostatic model assessment&amp;ndash;insulin resistance, C-reactive protein, and adiponectin).Results: We found that obese Scottish subjects had significantly higher serum RBP4 protein levels in comparison to the normal/overweight subjects (P &amp;lt; 0.01). Serum RBP4 levels were normalized in obese/diabetic subjects treated with diet or metformin (P &amp;lt; 0.05). Adipose tissue RBP4 protein levels were comparable between all three groups of subjects as were serum and adipose transthyretin levels. Adipose tissue PTP1B mRNA levels were increased in obese subjects in comparison to normal/overweight subjects (P &amp;lt; 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, while adipose tissue PTP1B mRNA levels increase in obese Scottish subjects, these remain high in obese/diabetics on diet or metformin treatment.Keywords: obesity, diabetes, metformin, PTP1B, RBP4, TTR, ER stress, UPR, GRP94, BIP, ATF4, insulin resistance, glucose homeostasi

Hoggard N

Agouni A

Mody N

Delibegovic M

Directory of Open Access Journals

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

Aberdeen University Research

Adipocyte-specific protein tyrosine phosphatase 1B deletion increases lipogenesis, adipocyte cell size and is a minor regulator of glucose homeostasis.

Adipocytokines and insulin resistance: The possible role of lipocalin-2, retinol binding protein-4, and adiponectin. Diabetes Care. 2009;32 Suppl 2:S362–S367.

Adipose tissue as an endocrine organ.

Attenuation of leptin action and regulation of obesity by protein tyrosine phosphatase 1B. Dev Cell.

Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes.

Decreased clearance of serum retinol-binding protein and elevated levels of transthyretin in insulin-resistant ob/ob mice.

Differential regulation of endoplasmic reticulum stress by protein tyrosine phosphatase 1B and T cell protein tyrosine phosphatase.

Editorial: Retinol-binding protein 4 and pathogenesis of diabetes.

Elevated retinol-binding protein 4 levels are associated with metabolic syndrome in Chinese people.

Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes.

Endoplasmic reticulum stress plays a central role in development of leptin resistance.

In vivo differential effects of fasting, re-feeding, insulin and insulin stimulation time course on insulin signaling pathway components in peripheral tissues.

Increased energy expenditure, decreased adiposity, and tissue-specific insulin sensitivity in protein-tyrosine phosphatase 1B-deficient mice.

Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene.

Liver-specif ic deletion of protein tyrosine phosphatase (PTP) 1B improves obesity- and pharmacologically-induced endoplasmic reticulum stress.

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Retinol-binding protein 4 and insulin resistance in lean, obese, and diabetic subjects.

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Shortcomings in methodology complicate measurements of serum retinol binding protein (RBP4) in insulin-resistant human subjects.

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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) 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

Hoggard, N

Agouni, A

Mody, N

Delibegovic, M

Surrey Research Insight

Serum Levels of Retinol Binding Protein 4 (RBP4) and Adipose Tissue Expression Levels of Protein Tyrosine Phosphatase 1B (PTP1B) are Increased in Obese Men Resident in North East of Scotland Without Any Changes in Endoplasmic Reticulum (ER) Stress Response Marker Genes

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3355846

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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