ANGPTL8 level after exercise.

<p><b>A</b>: Level of full length form of ANGPTL8 in non-obese subjects before and after three months of exercise training. <b>B</b>: Level of C-terminal 139–198 form of ANGPTL8 in non-obese subjects before and after three months of exercise training. <b>C</b>: Level of full length form of ANGPTL8 in obese subjects before and after three months of exercise training. <b>D</b>: Level of C-terminal 139–198 form of ANGPTL8 in obese subjects before and after three months of exercise training.</p

Spearman’s correlation between full length and C-terminal form of ANGPTL8 and FBG in non-obese subjects before and after exercise adjusted for age gender and BMI.

<p>Spearman’s correlation between full length and C-terminal form of ANGPTL8 and FBG in non-obese subjects before and after exercise adjusted for age gender and BMI.</p

An Immunohistochemical staining for subcutaneous adipose biopsies from non-obese (n = 10) and obese (n = 10) non-diabetic participants using ANGPTL7 antibody.

<p><b>B</b> Immunohistochemical staining of adipose tissue from obese subjects before exercise (n = 10) and after 3 months of exercise using ANGPTL7 antibody. Arrows indicate the positive staining. Aperio software was used for quantification and the values are illustrated at the bottom as fold changes after exercise. Student <i>t-test</i> for two group analysis was done to compare ANGPTL7 expression ^between non-obese, Paired t-test between obese before and after exercise. * <i>P</i>-Value < 0.05.</p

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

Spearman’s correlation between circulation level of ANGPTL7 and TG in the non-obese and the obese adjusted for age, gender and ethnicity.

<p>Spearman’s correlation between circulation level of ANGPTL7 and TG in the non-obese and the obese adjusted for age, gender and ethnicity.</p

Characteristics of the obese subjects before and after undertaking physical exercise.

<p>Characteristics of the obese subjects before and after undertaking physical exercise.</p

Characteristics of the non-obese and obese subjects included in this study.

<p>Characteristics of the non-obese and obese subjects included in this study.</p

Immunoblotting data from HEPG2 and 3T3-L1 cells showing increased ANGPTL7 protein expression and phospho-JNK after 125 μM palmitate treatment overnight compared to untreated controls.

<p>Immunoblotting data from HEPG2 and 3T3-L1 cells showing increased ANGPTL7 protein expression and phospho-JNK after 125 μM palmitate treatment overnight compared to untreated controls.</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

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