ANGPTL7 level after exercise.

<p><b>A</b>: Plasma level of ANGPTL7 in non-obese subjects (n = 82) before and after three months of physical exercise adjusted for age, gender and ethnicity. <b>B</b>: Plasma level of ANGPTL7 in obese subjects (n = 62) before and after three months of physical exercise adjusted for age, gender and ethnicity. <b>C</b>: Gene expression level of ANGPTL7 in adipose tissue in non-obese subjects before and after three months of physical exercise expressed as fold changes. <b>D</b>: Gene expression level of ANGPTL7 in adipose tissue in obese (n = 8) subjects before and after three months of physical exercise expressed as fold changes. * <i>P-Value</i> < 0.05 as determined using student’s t-test.</p

Proteomics Analysis of Human Obesity Reveals the Epigenetic Factor HDAC4 as a Potential Target for Obesity

<div><p>Sedentary lifestyle and excessive energy intake are prominent contributors to obesity; a major risk factors for the development of insulin resistance, type 2 diabetes and cardiovascular diseases. Elucidating the molecular mechanisms underlying these chronic conditions is of relevant importance as it might lead to the identification of novel anti-obesity targets. The purpose of the current study is to investigate differentially expressed proteins between lean and obese subjects through a shot-gun quantitative proteomics approach using peripheral blood mononuclear cells (PBMCs) extracts as well as potential modulation of those proteins by physical exercise. Using this approach, a total of 47 proteins showed at least 1.5 fold change between lean and obese subjects. In obese, the proteomic profiling before and after 3 months of physical exercise showed differential expression of 38 proteins. Thrombospondin 1 (TSP1) was among the proteins that were upregulated in obese subjects and then decreased by physical exercise. Conversely, the histone deacetylase 4 (HDAC4) was downregulated in obese subjects and then induced by physical exercise. The proteomic data was further validated by qRT-PCR, Western blot and immunohistochemistry in both PBMCs and adipose tissue. We also showed that HDAC4 levels correlated positively with maximum oxygen consumption (V_{O2 Max}) but negatively with body mass index, percent body fat, and the inflammatory chemokine RANTES. In functional assays, our data indicated that ectopic expression of HDAC4 significantly impaired TNF-α-dependent activation of NF-κB, establishing thus a link between HDAC4 and regulation of the immune system. Together, the expression pattern of HDAC4 in obese subjects before and after physical exercise, its correlation with various physical, clinical and metabolic parameters along with its inhibitory effect on NF-κB are suggestive of a protective role of HDAC4 against obesity. HDAC4 could therefore represent a potential therapeutic target for the control and management of obesity and presumably insulin resistance.</p> </div

Physical and clinical characteristics of 24 obese subjects before and after exercise.

<p><i>Data are presented as mean ± SD. Paired t-test was used to compare differences in obese before and after physical exercise.</i></p

Clinical and biochemical characteristics of subjects at baseline.

<p><i>Data were adjusted for age and gender and presented as mean ± SD. HR (heart rate), SBP (systolic blood pressure), DBP (diastolic blood pressure), V_{O2 Max} (maximum oxygen consumption), HDL (high density lipoprotein), LDL (low density lipoprotein) and TG (triglycerides).</i></p

Physical characteristics of subjects at baseline.

<p><i>Data are presented as mean ± SD. BMI (body mass index), PBF (percent body fat).</i></p

Obesity triggers a downregulation of DNAJB3 protein.

<p>(A) Total proteins were extracted from PBMC of lean (n = 4) and obese (n = 4) non-diabetic participants and subjected to western blot using the indicated antibodies. The bands were quantified as described in materials and methods and the relative intensity was determined after correction with actin that was used as internal control to monitor loading efficiency. The data are presented at the bottom as fold changes compared to lean group. The blots shown are representative of at least three independent experiments with consistent results. (B) Immunohistochemical staining using subcutaneous adipose biopsies from lean (n = 4) and obese (n = 11) non-diabetic participants. Aperio software was used to quantify positive staining (indicated by arrows) and the values are illustrated at the bottom as fold changes compared to lean. As negative control (NC) for the experiment, the primary antibodies were omitted. * <i>P</i><0.05 as determined using student's t-test.</p

Primer sequences used for real time PCR to analyze gene expression status of human heat shock-related genes.

<p>Primer sequences used for real time PCR to analyze gene expression status of human heat shock-related genes.</p