Heart Fat Infiltration In Subjects With and Without Coronary Artery Disease.

CONTEXT: Fat may accumulate around the heart in epicardial adipose tissue or inside the heart as lipid droplets (LDs). OBJECTIVE: To compare myocardial steatosis between subjects with and without coronary artery disease (CAD and non-CAD) and to identify which cells contain LDs. DESIGN: Body mass index, waist circumference, glucose, insulin, homeostasis model assessment index, leptin, adiponectin, and high-sensitivity C-reactive protein were evaluated in CAD and non-CAD subjects. Biopsies were collected from right atrial myocardium. Immunohistochemistry for perilipin (PLIN) 1 and 2 was used to characterize LDs and their localization in adipocytes or myocardial cells, respectively. Cardiomyocytes apoptosis and hypoxia inducible factor 1 alpha were obtained in a subgroup of subjects. SETTING: The study took place in a hospital. PATIENTS: Male subjects consecutively undergoing elective cardiac surgery either for coronary bypass grafting (CAD, n = 23) or for valve replacement (non-CAD, n = 18). MAIN OUTCOMES AND MEASURES: The study was designed to compare myocardial steatosis between subjects with and without coronary artery disease. RESULTS: PLIN1 and PLIN2 resulted significantly higher in CAD than in non-CAD subjects, as did apoptosis. PLIN1 was positively associated with circulating leptin, high-sensitivity C-reactive protein, and apoptosis, and negatively with adiponectin. PLIN2 was positively associated with body mass index, waist circumference, and leptin and negatively with adiponectin. After taking into account the absence/presence of hypertension, diabetes, and CAD/non-CAD, adiponectin was negatively associated with PLIN1 (r(2) = 0.532); waist circumference and adiponectin were associated with PLIN2 (r(2) = 0.399). CONCLUSIONS: Myocardial steatosis is greater in CAD than non-CAD subjects, depending on both metabolically active adipocytes interspersed among cardiomyocytes and higher fat deposition inside cardiomyocytes; serum adiponectin and waist circumference are independent predictors of myocardial steatosis.

Inflammatory profile in subcutaneous and epicardial adipose tissue in men with and without diabetes.

In recent years, evidence has emerged indicating that insulin resistance and diabetes mellitus type 2 are associated with inflammation of adipose tissue (AT). Interest has been focused on epicardial AT (EAT) because of its possible involvement with atherosclerosis and cardiovascular diseases. The aim of this study was to characterize adipocyte size and inflammatory profile in subcutaneous (SAT) and EAT among subjects with or without diabetes. Biopsies were collected from SAT and EAT in 34 men undergoing elective cardiac surgery. Weight, height, body mass index, waist circumference, as well as serum levels of glucose, insulin, lipids, adiponectin, and leptin were determined in all subjects. Adiponectin, MCP-1, and CD68 mRNA levels present within cells from AT biopsies were determined by real-time polymerase chain reaction. Adipocyte size was determined by optic microscopy and morphometry. Regarding the experimental group as a whole, gene-expression levels within EAT were significantly lower for adiponectin and higher, albeit not significantly, for MCP-1, when compared with that of SAT. In addition, adipocytes in EAT were significantly smaller than those in SAT. Subjects with diabetes showed lower adiponectin gene-expression levels in both SAT and EAT when compared with subjects without diabetes. By contrast, MCP-1 and CD68 gene-expression levels were higher in both tissue types of diabetic subjects. Adipocyte size in EAT was significantly larger in diabetic subjects than in nondiabetic subjects. Our data revealed a predominantly inflammatory profile in both SAT and EAT in subjects with diabetes in comparison with those without diabetes.

Myosteatosis and myofibrosis: relationship with aging, inflammation and insulin resistance.

The mechanisms impairing muscle quality and leading to myofibrosis (MF) and myosteatosis (MS) are incompletely known. In biopsies of paraspinous muscle (PM) of 16 elderly men undergoing elective vertebral surgery, we histologically determined the area of MF and MS expressed as muscle quality index (MQI), in order to investigate the relation between them, as well as the main predictors of muscle quality. Total PM area and intermuscular adipose tissue (IMAT) were evaluated by MRI and body composition by DXA. Circulating fasting glucose, insulin, hs-CRP, leptin, adiponectin and IL-6 were measured and HOMA index calculated. Quantification of gene expression in PM and in subcutaneous adipose tissue (SAT) overlying the muscle was performed by rt-PCR. The degree of MS and MF was significantly and positively related to each other and positively associated with BMI, waist, FM and FM% as well as with IMAT. The area of PM was negatively related with MF even after adjustment for weight. Leptin was positively associated with MF and MS, whereas hs-CRP to MF. In backward regression analyses, larger waist and smaller PM area explained 90% of MF variance, whereas leptin about 80% of MS variance. IL-6 expression in SAT was significantly higher in participants with higher MQI values. In PM biopsies we found significantly higher expression of SOCS-3 and a trend toward higher expression of myostatin with greater degrees of MQI. MS and MF are related phenomena that concur to alter muscle quality and both should be considered in further studies on the evolution of sarcopenia.

The association between excess weight and comorbidity and self-rated health in the Italian population.

PURPOSE: To evaluate the association of obesity with comorbidity and with subjective health perception in a large sample representative of the Italian population and how the association differs by age and gender. METHODS: Cross-sectional data were obtained from nine waves of the "Multipurpose Household Survey," conducted by the Italian National Institute of Statistics. Self-reported height and weight, six weight-associated diseases and self-rated health (SRH) were evaluated on 352,020 subjects aged 20 to 89 years. Comorbidity was defined as the presence of two or more diseases. RESULTS: The prevalence of comorbidity was significantly different between obese and normal weight subjects in all age categories. SRH was worse in obese subjects than in those of normal weight; this difference persisted, at least in females, into older ages. CONCLUSIONS: Obesity is associated with comorbidity and self-rated health; this association varies across ages and genders. The results found for obese subjects of a given age category were similar to (or worse than) those found for older normal weight subjects of the next age class. For comorbidity, this was true both in males and in females of all the considered age categories; for SRH, this was true in particular for females and younger males.

Sarcopenia, cachexia and congestive heart failure in the elderly.

Skeletal muscle abnormalities and loss are frequently present in patients with mild or moderate cardiac heart failure (CHF) and may contribute to fatigue and dyspnea. These muscle abnormalities may be associated with age related body composition changes, such as sarcopenia. Muscle damage has also been observed in subjects with cardiac cahexia, a serious CHF complication, associated with poor prognosis independently of functional disease severity, age, and measures of exercise capacity and cardiac function. Loss of muscle mass is a feature of cachexia, whereas most sarcopenic subjects are not cachectic. Individuals with no weight loss, no anorexia, and no measurable systemic inflammatory response may be sarcopenic. Patients with severe CHF show multiple marked histological abnormalities of skeletal muscle, such as muscle fiber atrophy. These abnormalities are different in sarcopenia and cachexia. The majority of mechanisms involved in sarcopenia play a role even in the determination of cachexia and they are amplified in cachexia where they may induce both muscle damage as well as other abnormalities, such as fat and weight loss, through activation of lypolisis or anorexia. To distinguish cachexia and sarcopenia in CHF patients, even if not easy, should be clinically relevant, because no specific treatment is available for cachectic patients whereas treatment options are possible for sarcopenia.

Adiponectin gene expression and adipocyte diameter: a comparison between epicardial and subcutaneous adipose tissue in men.

INTRODUCTION: Interest has recently focused on epicardial fat, but little is known about epicardial adipocyte size and its relation with insulin resistance and adipokines. METHODS: Biopsies were collected from subcutaneous, epicardial-, and peritoneal fat from 21 males undergoing elective cardiac surgery either for coronary artery bypass grafting (n=11) or for valve replacement (n=10). We assessed epicardial adipocyte size, comparing it with that from subcutaneous fat and peritoneal fat. The adipocyte size was determined by using collagenase digestion of adipose tissue, separation of adipocytes by centrifugation, methylene blue staining of the nuclei, and measurement of the cell diameter. Patient's weight, height, body mass index, waist, as well as glucose, insulin, homeostatic model assessment index, adiponectin, and leptin serum levels were determined. Adiponectin mRNA levels were determined by real-time polymerase chain reaction on subcutaneous fat and epicardial fat biopsies. RESULTS: Adipocytes in epicardial fat were significantly smaller than those in subcutaneous and peritoneal fat. The adipocyte size in epicardial fat correlated positively with insulin resistance and serum leptin, and correlated negatively with serum and mRNA expression of adiponectin. Adiponectin mRNA expression in epicardial fat was significantly lower than in subcutaneous fat. Adipocyte size in epicardial fat was significantly smaller in valve-replacement patients than in coronary artery bypass graft patients. Adiponectin gene expression was lower in the latter than in the former, although not significantly. CONCLUSIONS: Adipocytes in epicardial fat are smaller than those in peritoneal and subcutaneous fat. Adipocyte size, both in epicardial and in subcutaneous fat, is positively related with insulin resistance, shows negative association with local adiponectin gene expression, and is decreased in subjects with coronary artery disease. Adiponectin gene expression is significantly lower in epicardial- than in subcutaneous fat.

Quantification of intermuscular adipose tissue in the erector spinae muscle by MRI: agreement with histological evaluation.

Deposition of fat between skeletal muscle bundles and beneath the muscle fascia, recently called intermuscular adipose tissue (IMAT), is gaining attention as potential contributor to insulin resistance, metabolic syndrome, muscle function impairment, and disability. The aim of this study was to compare IMAT as measured at the erector spinae level by magnetic resonance imaging (MRI), a well-recognized gold standard method to evaluate fat content inside muscles, and histology estimates. In 18 healthy elderly men and women with a wide range of BMI (25.05-35.58 kg/m(2)), undergoing elective vertebral surgery, IMAT within the erector spinae muscle was evaluated by MRI, by body composition using dual-energy X-ray absorptiometry and histological evaluation of intraoperative biopsy sample. The concordance between IMAT/total area (TA) ratio evaluated by MRI and histological examination was analyzed employing Lin's concordance correlation coefficient and the procedure proposed by Bland and Altman. Two thresholds to distinguish between muscle and IMAT calculated, respectively, by 20 and 10% reduction of the gray-level intensity evaluated by MRI from surrounding subcutaneous adipose tissue (SAT) were used. With a 20% reduction, calculated IMAT/TA as evaluated by MRI on average exceeds histological evaluation by 21.79%, whereas by reducing the threshold by 10% agreement between MRI and histology improved with a 12.42% difference. Our data show a good degree of concordance between IMAT assessment by MRI and histology and seems to show that agreement between the two methods could be improved by using a more restrictive threshold between muscle and fat.