Obesity is a multifactorial disease presenting sex-related differences including adipocyte functions, sex hormone effects, genetics, and metabolic inflammation. These can influence individuals' risk ...for metabolic dysfunctions, with an urgent need to perform sex-based analysis to improve prevention, treatment, and rehabilitation programs. This research work is aimed at characterizing the transcriptional differences present in subcutaneous adipose tissue (SAT) of five obesity affected men versus five obesity affected women, with an additional focus on the role of long non-coding RNAs. Through RNA-sequencing, we highlighted the presence of both coding and non-coding differentially expressed RNAs, and with numerous computational analyses we identified the processes in which these genes are implicated, along with their role in co-morbidities development. We report 51 differentially expressed transcripts, 32 of which were coding genes and 19 were non-coding. Using the WGCNA R package (Weighted Correlation Network Analysis, version 1.70-3), we describe the interactions between coding and non-coding RNAs, and the non-coding RNAs association with the insurgence of specific diseases, such as cancer development, neurodegenerative diseases, and schizophrenia. In conclusion, our work highlights a specific gender sex-related transcriptional signature in the SAT of obesity affected patients.
Abstract Objective Previous studies have reported that patients with Parkinson’s disease (PD) have a favorable cardiometabolic risk profile. The aim of this study was to investigate the relationship ...between cardiometabolic risk factors and the duration of disease. Methods One hundred and fifty patients with PD (56.7% men) were studied, measuring body mass index (BMI), waist circumference (WC), body fat percentage (BF%) by impedance, fasting glucose, serum lipids, and transaminases. Results In sex- and age-adjusted correlation models, duration of PD was inversely related to BMI ( r = −0.20; P < 0.05) and BF% ( r = −0.29; P < 0.005). Using multivariable regression models (adjustments: age, gender, smoking status, levodopa dose and, alternatively, BMI, WC, or BF%), high-density lipoprotein (HDL) levels were positively correlated with disease duration ( P < 0.01 for all). In models adjusted for WC and BF%, total HDL-cholesterol ratio was also inversely associated with duration of PD ( P < 0.05 for both). No other association between biochemical variables and the duration of PD was found. Moreover, no dose–response effect of levodopa on metabolic risk factors was observed. Conclusions HDL levels and total HDL-cholesterol ratio were favorably associated with duration of PD. This factor may contribute to cardiometabolic protection in PD. The mechanisms underlying this association deserve further investigation.
Summary
Obesity is an evolutionary, chronic, and relapsing disease that consists of a pathological accumulation of adipose tissue able to increase morbidity for high blood pressure, type 2 diabetes, ...metabolic syndrome, and obstructive sleep apnea in adults, children, and adolescents. Despite intense research over the last 20 years, obesity remains today a disease with a complex and multifactorial etiology. Recently, long non‐coding RNAs (lncRNAs) are emerging as interesting new regulators as different lncRNAs have been found to play a role in early and late phases of adipogenesis and to be implicated in obesity‐associated complications onset. In this review, we discuss the most recent advances on the role of lncRNAs in adipocyte biology and in obesity‐associated complications. Indeed, more and more researchers are focusing on investigating the underlying roles that these molecular modulators could play. Even if a significant number of evidence is correlation‐based, with lncRNAs being differentially expressed in a specific disease, recent works are now focused on deeply analyzing how lncRNAs can effectively modulate the disease pathogenesis onset and progression. LncRNAs possibly represent new molecular markers useful in the future for both the early diagnosis and a prompt clinical management of patients with obesity.
Obesity is characterized by fat mass excess (FM), extra cellular water increase (ECW) and, with ageing, decrease in fat free mass (FFM). The validity of body impedance analysis (BIA) in patients with ...mild to severe obesity is still debated. The purpose of this study is to describe the Resistance (Rz) and Reactance (Xc) values obtained by Body Impedance Analysis (BIA) in a wide cohort of Italian patients with mild to severe obesity. The secondary endpoint is to describe the resulting body composition values (as percentage and indexes) in this population.
The study enrolled adult in-patients with mild to severe obesity (classified with class I, II and III obesity) undergoing clinical care rehabilitation program for obesity complications and weight loss. BIA values were grouped by sex, BMI and age classes.
A total of 8303 patients with obesity, aged 18 to 90 y, were studied. The Resistance (Rz) and Reactance (Xc) were reported by sex, age and BMI classes. In women and men both, the phase angle (PhA) decreases with increasing BMI (kg/m2) and the resulting BIA vector was significantly shifted. The FM index (FMI) was higher (p < 0.0001) in women while FFM index (FFMI) was higher in men (p < 0.0001) and significantly associated with BMI. FFMI decreased with age in both sex (p < 0.0001). Skeletal mass (SM) presents a progressive reduction in relation to age and gender both.
The present BIA-based body composition analysis in a wide cohort of mild to severe obese patients revealed a significantly decreased Rz and Xc values with a consequent significant decrease of PhA in a BMI-dependent manner. The body compartments estimation with available equations was BMI, sex and age dependent. These observational results could be the basis for the development of new equations adapted for patients suffering from obesity.
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•BIA in patients with severe obesity is debated.•PhA decreases with increasing BMI.•BIA ranges in severe obesity were shown.
Phase angle (PhA) is a recently proposed marker of nutritional status in many clinical conditions. Its use in patients with obesity presents different critical concerns due to the higher variability ...of the two measured parameters (resistance, R, and reactance, Xc) that contribute to the determination of PhA. Controversial is the relation between PhA and BMI that might vary with graded levels of obesity due to the variation in fat and free fat mass. Obesity is frequently associated with metabolic, hepatic, cardiovascular and kidney diseases that introduce variations in PhA values, in relation to multimorbidity and severity degree of these diseases. It is reported that the improvement of clinical condition is associated with a positive change in PhA. Also, the treatment of obesity with weight loss might confirm this effect, but with different responses in relation to the type and duration of the intervention applied. In fact, the effect appears not only related to the percentage of weight loss but also the possible loss of free fat mass and the nutritional, metabolic and structural modifications that might follow each therapeutic approach to decrease body weight. We can conclude that the PhA could be used as marker of health status in patients with obesity supporting an appropriate weight loss intervention to monitor efficacy and fat free mass preservation.
Crohn's disease (CD) is a chronic inflammatory bowel disease characterised by a peculiar accumulation of mesenteric adipose tissue covering the inflamed intestinal wall.
The authors characterised ...different adipose tissue compartments of patients with CD using morphological and molecular techniques and compared them to those of subjects with obesity (OB) and healthy subjects with normal weight (N). Adipose tissue samples were taken from subcutaneous adipose tissue, omental visceral adipose tissue (VAT) and healthy mesenteric depot (hMES), as well as from fat wrapping the affected (unhealthy) intestinal tracts (uhMES). Microarray analyses, validated by real-time quantitative PCR technique, were performed in whole adipose tissue and in isolated adipocytes.
The morphology of subcutaneous adipose tissue was similar in subjects with CD and those with N. In patients with CD, VAT adipocytes were smaller than those derived from uhMES and hMES and were smaller than VAT adipocytes of subjects with N. The molecular profiles of CD, VAT and uhMES were characterised by upregulation of genes related to inflammation and downregulation of those involved in lipid metabolism. Adipocytes isolated from VAT of subjects with CD and those with OB exhibited similar upregulation of genes involved in inflammation and immunity. VAT adipocytes of patients with CD compared to those of patients with OB also showed a greater upregulation of several anti-inflammatory genes.
In patients with CD, VAT distant from uhMES is affected by inflammation and displays features similar to those of VAT of patients with severe OB. The small diameter of VAT adipocytes of CD, together with their high expression of anti-inflammatory genes, suggests a potentially protective role for this tissue. VAT adipocytes may play an important role in the pathophysiology and/or activity of CD.
ABSTRACT
The concept that adipocytes belong to an essential endocrine system with some characteristics of immune cells has recently emerged. The aim of this paper is to present evidence of the ...expression of CD4, CXCR4, and CCR5 receptors by human adipocytes and to test whether adipose cells support HIV entry. Primary human preadipocytes were cultured and differentiated in vitro. Expression of the three receptors on preadipocytes and adipocytes was demonstrated by reverse transcriptase‐polymerase chain reaction, immunocytochemical, and immunohistochemical analysis. Infection of adipose cells to HIV‐1 was then investigated. The measurement of the viral p24 antigen in preadipocyte culture medium showed an increase of p24 levels between 24 and 72 h postexposure and then a progressive decrease to reach a low level at 10–15 days. Ten days after the infection test, supernatant of preadipocytes contained infectious particles able to infect the susceptible T‐CD4 CEM cell line. The expression of viral proteins by adipocytes was confirmed using a fusion test. The presence of viral DNA was exhibited by gag‐specific polymerase chain reaction, supporting the hypothesis of HIV‐1 X4‐ and R5‐virus entry in preadipocytes. Adipose cells represent the first cell type that does not belong to the immune system expressing all specific HIV receptors and may represent new HIV‐1 target cells.
Patients with advanced Parkinson's disease (PD) experience body weight loss and reductions in the most common cardiovascular risk factors. At present, the pathogenetic mechanisms involved have not ...been elucidated. Increased serum concentrations of adiponectin, which possesses antiatherogenic and anti-inflammatory properties, are associated with a reduction in cardiovascular risk. The objective of this study was to determine adiponectin serum concentrations in PD patients. Thirty PD patients underwent a full nutritional status assessment, including the determination of adiponectin serum concentrations. Mean ± SD adiponectin concentrations were 9.59 ± 5.9 μg/mL (interquartile range: 5.92–12.9 μg/mL). In PD patients, adiponectin serum levels were similar to those in normal-weight, healthy, young subjects and significantly higher than that in an aged-matched group of morbidly obese subjects. Further studies are warranted to establish the role of adiponectin in the management of PD patients.
Uncoupling protein 1 (UCP1), the mammalian thermogenic mitochondrial protein, is found only in brown adipocytes, but its expression by immunohistochemistry is not homogeneous. Here we present ...evidence that the non-homogeneous pattern of immunostaining for UCP1 (referred to as the “Harlequin phenomenon”) is particularly evident after acute and chronic cold (4C) stimulus and after administration of a specific β3-adrenoceptor agonist (CL316,243). Accordingly, mRNA in situ expression confirmed the UCP1 non-homogeneous pattern of gene activation under conditions of adrenergic stimulus. Furthermore, morphometric analysis of immunogold-stained thin sections showed that UCP1-gold particle density was different among neighboring brown adipocytes with mitochondria of the same size and density. When the adrenergic stimulus was reduced in warm-acclimated animals (28C), UCP1 protein and mRNA expression was reduced and consequently the Harlequin phenomenon was barely visible. These data suggest the existence of an alternative and controlled functional recruitment of brown adipocytes in acute adrenergically stressed animals, possibly to avoid heat and metabolic damage in thermogenically active cells. Of note, the heat shock protein heme oxygenase 1 (HO1) is heterogeneously expressed in adrenergically stimulated brown adipose tissue and, specifically, cells expressing strong immunoreactivity for UCP1 also strongly express HO1.
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