Metabolic Activity Of Adipose Tissue Research Articles

A case of chronic tophi gout in morbidly obese patient after laparoscopic adjustable gastric banding

Currently, increasing attention is being paid to studying the metabolic activity of adipose tissue, a source of biologically active mediators involved in vascular remodeling, immunological and inflammatory reactions. Today obesity is considered not only as independent risk factor of development of chronic noninfectious diseases (such as arterial hypertension, diabetes mellitus types 2, pathology of a cardiovascular system, malignant neoplasms), but also as a significant predictor of metabolic disorders (dyslipidemia, insulin resistance, hyperuricemia), contributes to the early formation of metabolic syndrome and goat. Despite such an obvious problem, the current state of conservative therapy for overweight and obesity remains unsatisfactory. Most of patients, even after successful treatment, have a recurrence of the disease with the restoration of the initial anthropometric indicators or even an increase in body weight. In this regard, currently more widely used surgical methods of correction of obesity. However along with the expected positive effects of treatment bariatric surgery may be accompanied by the development of a number of specific surgical complications and impaired energy metabolism with aggravation of the existing polymorbid pathology. This clinical case demonstrates the association of obesity with the development of metabolic disorders, illustrates the development of severe tophaceous gout in a patient during 2 years after laparoscopic gastric banding. It shows the possible reasons for its debut and reflects the dynamics of the patients condition, as well as the nature and characteristics of the course of the joint syndrome in the postoperative period.

Особливості гормонального балансу та метаболічного профілю у вагітних з різними типами ожиріння

Maternal obesity has become one of the main factors influencing obstetric and perinatal outcomes. Obesity in pregnant women increases the risk of complications during pregnancy, childbirth and the postpartum period. The newborns of obese women also have higher rates of perinatal morbidity and an increased risk of long-term health problems. The objective: to learn hormonal and metabolic peculiarities in pregnant women with different obesity types during full-term pregnancy. Materials and methods. We examined 61 pregnant women with android type and 57 pregnant women with gynoid type of obesity at 39.6–40.6 weeks of gestation and 57 pregnant women without obesity and overweight. The concentration of estradiol, free estriol, insulin, placental lactogen, free testosterone, cortisol, dehydroepialdosterone sulfate (DHEA sulfate), and serum progesterone by enzyme-linked immunosorbent method and glucose rate by glucose-oxydase method were determined. The HOMA index was determined. Results. In pregnant women with gynoid obesity type, the level of progesterone was 41.15 (34.6–48) ng/ml, with android type – 35.7 (32.6–40.6) ng/ml and with physiological body weight 35.4 (33.2–40) ng/ml (p<0.05). While determining the concentration of placental lactogen in three groups there were no significant differences. There was a decrease (p<0,05) in the level of free estriol in groups of pregnant women with android and gynoid type of obesity in comparison with the control group, respectively 13.9 (13.1–14.9) ng/ml, 13.6 (12, 4–15.4) ng/ml and 14.7 (13.6–15.8) ng/ml. The concentration of estradiol in second group was 24 925.3 (20 206.6–30 400.5) pg/ml, which is 1.2 times (p<0.05) higher as in the control group and 1.4 times higher as in first group. In pregnant women with android-type obesity, estradiol levels were 1.2 times lower (p<0.05) compared with the control group. The concentration of cortisol in pregnant women with android type was 812.1 (599–1235.15) nmol/l, which is 2.7 times higher (p<0.05) compared to the women with gynoid type of obesity and 1.5 times higher (p<0.05) than in the control group. In pregnant women with gynoid type of obesity, 1.7 times lower (p<0.05) cortisol levels were observed in comparison with control group. The level of free testosterone was 2.4 (1.7–3.1) nmol/l in pregnant women of first group, what was higher (p<0.05) than in second group and in control group, respectively 1 (0.8–1.5) nmol/l and 1.9 (1.6–2.3) nmol/l. Pregnant women in group 1 had 2.4 times higher (p<0.05) testosterone levels compared to group 2 and 1.2 times higher (p<0.05) than in control group. In women with android type, the concentration of DHEA sulfate was 2.4 times higher (p<0.05) than in pregnant women with gynoid type and 2.1 times higher (p<0.05) compared with the control group. Pregnant women with android type of obesity have a significantly higher (p<0.05) serum insulin concentration of 67 (40–94.5) μIU / ml compared to women with gynoid type of obesity 33.3 (25.6–43) μIU/ml. When determining the glucose concentration no significant difference between three groups was found. The HOMA index in pregnant women with android type of obesity was 2.1 times higher than in pregnant women with gynoid type and 2.3 times higher than in control group (p<0.05). Conclusions. The results of a study indicate that the type of distribution of adipose tissue is important during pregnancy and childbirth because the hormonal and metabolic activity of adipose tissue in android and gynoid obesity types are different. Keywords: android type of obesity, pregnancy, gynoid type of obesity, hormonal balance, metabolic profile.

Prognostic significance of adipose tissue distribution and metabolic activity in PET-CT images of patients with metastatic colorectal cancer.

e16038 Background: The metabolic activity in visceral and subcutaneous adipose tissue have different metabolic risk profiles for colorectal cancer. The aim of this study was to investigate the prognostic significance of adipose tıssue distribution and metabolic activity in PET-CT and predict the overall survival in patients with metastatic colorectal cancer (mCRC). Methods: A total of 83 patients diagnosed with mCRC between 2010-2018 were evaluated retrospectively. Pretreatment PET-CT images were reevaluated to determine adipose tissue distribution and metabolic activity. Volume and metabolic activity of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) on FDG PET-CT images were measured. SAT volume, SAT density (HU), SAT ratio (SAT volume/ SAT density) were calculated. The maximum standardized uptake (SUV) of tumor tissue was measured. The relationship between adipose tissue and overall survival was examined. Results: 53 patients died during follow-up and the median overall survival was 33.76 months (95% CI: 28.185-39.349). According to univariate analysis results, tumor location (HR:2.5; 95% CI 1.27-4.98, p = 0.008) and SAT ratio (HR:0.5; 95% CI 0.34-1.00, p = 0.053) were the significant parameters for the OAS. VAT volume (p = 0.774), VAT density (p = 0.899), VAT suv mean (p = 0.831) and SAT volume (p = 0.423), SAT density (p = 0.353), SAT suv mean (p = 0.575), tumor suv max (p = 0.589) values were not correlated with OAS. In the multivariate analysis, SAT ratio (p = 0.011) and tumor location (p = 0.001) were correlated significantly with OAS. The median OAS for the patients with SAT ratio value < -1.1 and -1.1 were 38.5 (95% CI 31.54-45.58) and 24.5 (95% CI 14.13-34.93) months, respectively (p = 0.05). Conclusions: This study showed that SAT ratio was an independent prognostic factor for OAS in patients with mCRC. We need prospective studies for to observe the relationship between adipose tissue distribution and response to treatment in mCRC.

Association of obesity and anovulatory infertility.

ABSTRACTObjectiveTo verify the association of obesity and infertility related to anovulatory issues.MethodsThis case-control study was carried out with 52 women, aged 20 to 38 years, divided into two groups (infertile − cases − and fertile − control), seen at outpatient clinics, in the period from April to December, 2017.ResultsWe found significant evidence that obesity negatively affects women’s fertility (p=0.017). The group of infertile women was 7.5-fold more likely to be obese than fertile women.ConclusionStrategies that encourage weight control are indicated for women with chronic anovulation, due to hight metabolic activity of adipose tissue.

Genetic deletion of mast cell serotonin synthesis prevents the development of obesity and insulin resistance

Obesity is linked with insulin resistance and is characterized by excessive accumulation of adipose tissue due to chronic energy imbalance. Increasing thermogenic brown and beige adipose tissue futile cycling may be an important strategy to increase energy expenditure in obesity, however, brown adipose tissue metabolic activity is lower with obesity. Herein, we report that the exposure of mice to thermoneutrality promotes the infiltration of white adipose tissue with mast cells that are highly enriched with tryptophan hydroxylase 1 (Tph1), the rate limiting enzyme regulating peripheral serotonin synthesis. Engraftment of mast cell-deficient mice with Tph1−/− mast cells or selective mast cell deletion of Tph1 enhances uncoupling protein 1 (Ucp1) expression in white adipose tissue and protects mice from developing obesity and insulin resistance. These data suggest that therapies aimed at inhibiting mast cell Tph1 may represent a therapeutic approach for the treatment of obesity and type 2 diabetes.

Pleiotropic effects of apolipoprotein A-Ⅱ on high-density lipoprotein functionality, adipose tissue metabolic activity and plasma glucose homeostasis.

Apolipoprotein A-Ⅱ (APOA-Ⅱ) is the second most abundant apolipoprotein of high-density lipoprotein (HDL) synthesized mainly by the liver and to a much lesser extent by the intestine. Transgenic mice overexpressing human APOA-Ⅱ present abnormal lipoprotein composition and are prone to atherosclerosis, though in humans the role for APOA-Ⅱ in coronary heart disease remains controversial. Here, we investigated the effects of overexpressed APOA-Ⅱ on HDL structure and function, adipose tissue metabolic activity, glucose tolerance and insulin sensitivity. C57BL/6 mice were infected with an adenovirus expressing human APOA-Ⅱ or a control adenovirus AdGFP, and five days post-infection blood and tissue samples were isolated. APOA-Ⅱ expression resulted in distinct changes in HDL apoproteome that correlated with increased antioxidant and anti-inflammatory activities. No effects on cholesterol efflux from RAW 264.7 macrophages were observed. Molecular analyses in white adipose tissue (WAT) indicated a stimulation of oxidative phosphorylation coupled with respiration for ATP production in mice overexpressing APOA-Ⅱ. Finally, overexpressed APOA-Ⅱ improved glucose tolerance of mice but had no effect on the response to exogenously administered insulin. In summary, expression of APOA-Ⅱ in C57BL/6 mice results in pleiotropic effects with respect to HDL functionality, adipose tissue metabolism and glucose utilization, many of which are beneficial to health.

Metabolic Crosstalk between the Heart and Fat

It is now recognized that the heart can behave as a true endocrine organ, which can modulate the function of other tissues. Emerging evidence has shown that visceral fat is one such distant organ the heart communicates with. In fact, it appears that bi-directional crosstalk between adipose tissue and the myocardium is crucial to maintenance of normal function in both organs. In particular, factors secreted from the heart are now known to influence the metabolic activity of adipose tissue and other organs, as well as modulate the release of metabolic substrates and signaling molecules from the periphery. This review summarizes current knowledge regarding primary cardiokines and adipokines involved in heart-fat crosstalk, as well as implications of their dysregulation for cardiovascular health.

P730Decreased adiponectin levels and FDG uptake in visceral adipose tissue in familial combined hyperlipidemia compared to heterozygous familial hypercholesterolemia and normolipidemics

Abstract Background Adipose tissue regulates energy balance and glucose homeostasis via the secretion of circulating molecules, termed adipokines, such as leptin and adiponectin. Excess adiposity and adipose tissue dysfunction have been involved in the pathogenesis of dyslipidemias. Positron emission tomography/computed tomography (PET/CT) with F-18-Fluorodeoxyglycose (FDG) has been used for the assessment of adiposity. Purpose To compare abdominal adipose tissue function assessed by FDG uptake with serum indices, such as plasma adipokines' levels in individuals with different subtypes of dyslipidemia and normolipidemics. Methods Seventy individuals (mean age 44±13 years, range 21–75, 43 men) with a clinical diagnosis of either heterozygous familial hypercholesterolemia (heFH) (n=38) or familial combined hyperlipidemia (FCH) (n=32), not under statins for at least one year, and 20 age and sex matched controls, were enrolled. Visceral (VAT) and subcutaneous adipose tissue metabolic activity (SAT) was assessed with FDG-PET/CT imaging and was quantified by calculating the target-to-background ratios (TBR) in consecutive axial fat images between the proximal (cephalic) end of the L1 and distal (caudal) end of the L3 vertebrae by dividing the average of the mean standard uptake value (SUV) to the mean SUV of the vena cava. Leptin and adiponectin were measured in all the subjects. Results There was no significant difference of plasma leptin values between FCH, heFH and non dyslipidemics subjects (p=0.204). FCH had reduced adiponectin values compared to heFH patients and controls [median 5.7 IQR (3.9–7.6) vs. 13.1 (9.2–23.3) vs. 10.9 (6.1–19.1) μg/mL, respectively, p<0.001]. There was no difference in FDG uptake in subcutaneous adipocytes (SATTBR) between FCH, heFH and controls (p=0.161). In contrast, patients with FCH had reduced VATTBR values compared to heFH patients and controls (0.63±0.14 versus 0.81±0.17 versus 0.86±0.28, p=0.005). This difference remained significant even after adjustment for age, sex and cardiovascular risk factors (b=-0.428, p=0.001, adjusted R2=0.219). SATTBR was inversely correlated to leptin levels (r=−0.484, p<0.001), while no significant association was observed with adiponectin values (p=0.167). No significant associations were observed between VATTBR and either serum leptin (p=0.066) or adiponectin levels (p=0.254). Conclusions Visceral adipose tissue FDG uptake is reduced in patients with FCH compared to those with heFH and normolipidemics. In addition, serum adiponectin levels are lower in patients with FCH. These findings highlight the different pathophysiological role of visceral fat function in the two most common types of familial dyslipidemia and suggest that visceral fat could be an attractive target for the treatment of FCH.

Abstract P2052: Differential Association of Measures of Adiposity With 24-Hour Ambulatory Blood Pressure Control in Adults on Antihypertensive Monotherapy

Background: Regional measures of adipose distribution, such as visceral adiposity and waist circumference, are more strongly associated with metabolic activity of adipose tissue and longitudinal cardiovascular risk than broader metrics, such as body mass index (BMI) and total fat mass. Little is known about the differential relationship of BMI, waist circumference, visceral adiposity, and total fat mass with degree of blood pressure (BP) control on 24-hour ambulatory BP monitoring (ABPM) in adults with hypertension (HTN). Methods: We performed 24-hour ABPM in adults recruited from primary care clinics with a diagnosis of HTN on a stable dose of a single antihypertensive agent. Dual x-ray absorptiometry (DXA) was performed to determine visceral adiposity and total fat mass (indexed by height). Results: Of the 97 participants, mean age was 56 (+/- 13) years, with 56 (58%) women, 46 (47%) black, 28 (29%) with diabetes, and 13 (13%) smokers. Mean BMI was 31.7 (+/- 7.2) kg/m 2 and mean waist circumference was 104 (+/- 17) cm. Mean 24-hour systolic BP (SBP) was 135 (+/- 13) mmHg, mean 24-hour SBP average real variability (ARV) was 13 (+/- 3), 47 (48%) were non-dippers, 26 (27%) had masked HTN, and 21 (22%) had uncontrolled HTN. After adjusting for age, sex, race, and antihypertensive class, the highest quartiles of waist circumference and visceral adiposity were associated with higher 24-hour mean SBP (waist circumference β = 9.5, 95% CI 1.9-17.2; visceral adiposity β = 8.6, 95% CI 0.5-16.8) and SBP ARV (waist circumference β = 2.8, 95% CI 1.0 to 4.6; visceral adiposity β = 2.9, 95% CI 1.1 to 4.7) compared to the lowest quartiles; BMI and total fat mass were not associated with these ABPM parameters. Individuals in the highest quartile of visceral adiposity had a 6.3-fold greater odds (95% CI 1.2-33.1) of masked HTN compared to the lowest quartile; no other adiposity measures were associated with masked HTN. Conclusions: Elevated visceral adiposity is associated with high 24-hour SBP and SBP variability in individuals with HTN. Unlike other measures of adiposity, higher visceral adiposity is strongly linked with masked hypertension. Measurement of visceral adiposity may help to identify those individuals who would benefit most from 24-hour ABPM to screen for masked hypertension.

Exercise training alters lipoprotein particles independent of brown adipose tissue metabolic activity.

SummaryIntroductionNew strategies for weight loss and weight maintenance in humans are needed. Human brown adipose tissue (BAT) can stimulate energy expenditure and may be a potential therapeutic target for obesity and type 2 diabetes. However, whether exercise training is an efficient stimulus to activate and recruit BAT remains to be explored. This study aimed to evaluate whether regular exercise training affects cold‐stimulated BAT metabolism and, if so, whether this was associated with changes in plasma metabolites.MethodsHealthy sedentary men (n = 11; aged 31 [SD 7] years; body mass index 23 [0.9] kg m−2; VO2 max 39 [7.6] mL min−1 kg−1) participated in a 6‐week exercise training intervention. Fasting BAT and neck muscle glucose uptake (GU) were measured using quantitative [18F]fluorodeoxyglucose positron emission tomography–magnetic resonance imaging three times: (1) before training at room temperature and (2) before and (3) after the training period during cold stimulation. Cervico‐thoracic BAT mass was measured using MRI signal fat fraction maps. Plasma metabolites were analysed using nuclear magnetic resonance spectroscopy.ResultsCold exposure increased supraclavicular BAT GU by threefold (p < 0.001), energy expenditure by 59% (p < 0.001) and plasma fatty acids (p < 0.01). Exercise training had no effect on cold‐induced GU in BAT or neck muscles. Training increased aerobic capacity (p = 0.01) and decreased visceral fat (p = 0.02) and cervico‐thoracic BAT mass (p = 0.003). Additionally, training decreased very low‐density lipoprotein particle size (p = 0.04), triglycerides within chylomicrons (p = 0.04) and small high‐density lipoprotein (p = 0.04).ConclusionsAlthough exercise training plays an important role for metabolic health, its beneficial effects on whole body metabolism through physiological adaptations seem to be independent of BAT activation in young, sedentary men.

Impact of apolipoprotein A1‐ or Lecithin:cholesterol acyltransferase‐deficiency on white adipose tissue metabolic activity and glucose homeostasis in mice

High density lipoprotein (HDL) has attracted the attention of the biomedical community due to its well‐documented role in atheroprotection. HDL has been recently implicated in the regulation of islets of Langerhans secretory function and in the etiology of peripheral tissue insulin sensitivity. Indeed, data from numerous studies strongly indicate that β‐cells, as well as skeletal muscles and adipose tissue could benefit from improved HDL functionality. To better understand how changes in HDL structure may affect diet‐induced obesity and type 2 diabetes we aimed at investigating how deficiency in Apoa1 or Lcat, two key proteins of peripheral HDL metabolic pathway, could affect these pathological conditions in mouse models. We report that universal deletion of apoa1 or lcat expression in mice fed western‐type diet results in increased sensitivity to body‐weight gain compared to control C57BL/6 group. These changes in mouse genome correlate with discreet effects on WAT metabolic activation and plasma glucose homeostasis. Apoa1‐deficiency results in reduced WAT mitochondrial non‐shivering thermogenesis. Lcat‐deficiency causes a concerted reduction in both WAT oxidative phosphorylation and non‐shivering thermogenesis, rendering lcat−/− mice the most sensitive to weight gain out of the three strains tested, followed by apoa1−/− mice. Nevertheless, only apoa1−/− animals show disturbed plasma glucose homeostasis due to non‐responsive pancreatic β‐islets to glucose and insulin resistant skeletal muscles. Our analyses show that both apoa1−/− and lcat−/− mice fed high‐fat diet have no measurable Apoa1 levels in their plasma, suggesting that other HDL components may be responsible for the observed phenotypic differences among groups.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Impact of apolipoprotein A1- or lecithin:cholesterol acyltransferase-deficiency on white adipose tissue metabolic activity and glucose homeostasis in mice

High density lipoprotein (HDL) has attracted the attention of biomedical community due to its well-documented role in atheroprotection. HDL has also been recently implicated in the regulation of islets of Langerhans secretory function and in the etiology of peripheral insulin sensitivity. Indeed, data from numerous studies strongly indicate that the functions of pancreatic β-cells, skeletal muscles and adipose tissue could benefit from improved HDL functionality. To better understand how changes in HDL structure may affect diet-induced obesity and type 2 diabetes we aimed at investigating the impact of Apoa1 or Lcat deficiency, two key proteins of peripheral HDL metabolic pathway, on these pathological conditions in mouse models. We report that universal deletion of apoa1 or lcat expression in mice fed western-type diet results in increased sensitivity to body-weight gain compared to control C57BL/6 group. These changes in mouse genome correlate with discrete effects on white adipose tissue (WAT) metabolic activation and plasma glucose homeostasis. Apoa1-deficiency results in reduced WAT mitochondrial non-shivering thermogenesis. Lcat-deficiency causes a concerted reduction in both WAT oxidative phosphorylation and non-shivering thermogenesis, rendering lcat−/− mice the most sensitive to weight gain out of the three strains tested, followed by apoa1−/− mice. Nevertheless, only apoa1−/− mice show disturbed plasma glucose homeostasis due to dysfunctional glucose-stimulated insulin secretion in pancreatic β-islets and insulin resistant skeletal muscles. Our analyses show that both apoa1−/− and lcat−/− mice fed high-fat diet have no measurable Apoa1 levels in their plasma, suggesting no direct involvement of Apoa1 in the observed phenotypic differences among groups.

The role of system inflammation in bronchial asthma and obesity

The prevalence of bronchial asthma and obesity has grown in the recent decades worldwide. The urgency of this problem due to its medical and social significance for the society in connection with a reduction of patients ‘ quality of life and considerable economic damage to the health system. The relationship of these diseases, there are gender-related, age-related characteristics no doubt. Growing clinical-epidemiological evidence indicates that obesity might be an independent risk factor for bronchial asthma. On the other hand, the clinical data of bronchial asthma is a consequence of obesity remain indicative. The presence of concomitant obesity, bronchial asthma is considered as a state, significantly worsens its course. Etiology the causal relationship between obesity and asthma, despite the proposed mechanical, immunological, genetic and hormonal concepts still remains unclear. The underlying mechanism for this association is still unclear although several theories have been postulated in an attempt to describe it. Many studies demonstrate that bronchial asthma and obesity have some common mechanisms, including chronic systemic inflammation. In the review, we outline the current understanding of the role of systemic inflammation linked to obesity in the pathophysiology of bronchial asthma. An important role in the pathophysiology of systemic inflammation is given to changing levels of key adipose tissue hormones - leptin and adiponectin, respectively, having proinflammatory and anti-inflammatory activity. '/'his review article will focus on the leptin and adiponectin. Understanding the mechanisms of correlation between the metabolic activity of adipose tissue and the functional status of the respiratory tract with the development of systemic inflammation with comorbid asthma and obesity will review a number of existing provisions for the diagnosis and treatment of associated course of these diseases, to expand understanding the phenotypes of asthma and to develop new treatment strategies.

Evaluation of Glucose Uptake and Uncoupling Protein 1 Activity in Adipose Tissue of Diabetic Mice upon β-Adrenergic Stimulation.

Regulation of metabolic activity in adipose tissue is of great concern for treating obesity. This study aimed to evaluate the adrenergic regulation of glucose uptake and the thermogenic program in adipose tissues in mouse models of both type 1 and 2 diabetes mellitus (DM). Male mice were treated with streptozotocin to induce type 1 (T1) DM, and obese ob/ob mice were used for the type 2 (T2) DM model. After selective β3-adrenoreceptor stimulation by CL 316,243 (CL) treatment, 2-deoxy-D-[14C]glucose ([14C]DG) was administered to DM and corresponding control mice. Radioactivity and uncoupling protein 1 (UCP1) expression were measured and analyzed in adipose tissues. In T1DM, [14C]DG uptake in brown adipose tissue (BAT) decreased both at rest and upon CL stimulation, and UCP1 expression was preserved. However, CL treatment enhanced [14C]DG uptake without impairing UCP1 expression in inguinal white adipose tissue (iWAT). In this model, CL could not alter blood glucose levels. In T2DM mice, the blood glucose level was significantly lowered by CL treatment. There was no decrease in CL-induced [14C]DG uptake in BAT, and UCP1 expression was maintained. However, [14C]DG uptake was not increased in iWAT and no UCP1 expression was observed in iWAT (browning). The metabolic response against adrenergic stimulation varied depending on the type of adipose tissue and DM. This could be important for the therapeutic activation of adipose tissue metabolism in obese diabetic patients.

Usefulness of metabolic activity of adipose tissue in FDG PET/CT of colorectal cancer.

To determine the relationship between metabolic activity of adipose tissue on FDG PET/CT and prognosis in colorectal cancer. A total of 176 colorectal cancer patients with curative surgical resection were retrospectively enrolled. Volume and metabolic activity of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) on FDG PET/CT images were measured. The maximum standardized uptake value (SUV) of primary tumor (SUVtumor) was also obtained. Univariate analysis with log-rank test and multivariate Cox regression analyses were used to evaluate prognostic values of volume and metabolic activity of SAT and VAT as well as SUVtumor and clinicopathologic factors. Of 176 patients, 26 experienced recurrence during follow-up. SUVtumor showed significant correlation with serum C-reactive protein level (r=0.242, p=0.001), SUV of VAT (r=0.167, p=0.026), and size of primary tumor (r=0.341, p<0.001). In univariate analysis with log-rank test, SUV of VAT (p=0.009) and SAT (p=0.006), volume of VAT (p=0.015), N stage (p<0.001), M stage (p<0.001), tumor involvement of resection margin (p=0.001), and lymphatic invasion (p=0.024) were significantly associated with recurrence-free survival (RFS). However, SUVtumor showed no significant association with RFS. In multivariate Cox regression analysis, SUV of VAT (p=0.016), presence of lymph node metastasis (p<0.001), and tumor involvement of resection margin (p=0.011) were independent prognostic factors for RFS. The SUV of VAT in patients with colorectal cancer is significantly associated with FDG uptake of primary tumor. It is an independent predictor for RFS.

Specific metabolic characteristics of women with former gestational diabetes: the importance of adipose tissue.

Women with a positive history of gestational diabetes mellitus (GDM) face a higher risk of developing type 2 diabetes mellitus (T2DM) and metabolic syndrome later in life. The higher risk of these metabolic complications is closely associated with adipose tissue. In this review, the importance of adipose tissue is discussed in relation to GDM, focusing on both the quantity of fat deposits and the metabolic activity of adipose tissue in particular periods of life: neonatal age, childhood, adolescence, and pregnancy followed by nursing. Preventive measures based on body composition and lifestyle habits with special attention to the beneficial effects of breastfeeding are also discussed.

Pleiotropic effects of apolipoprotein C3 on HDL functionality and adipose tissue metabolic activity

APOC3 is produced mainly by the liver and intestine and approximately half of plasma APOC3 associates with HDL. Though it was believed that APOC3 associates with HDL by simple binding to preexisting particles, recent data support that biogenesis of APOC3-containing HDL (APOC3-HDL) requires Abca1. Moreover, APOC3-HDL contributes to plasma triglyceride homeostasis by preventing APOC3 association with triglyceride-rich lipoproteins. Interestingly, APOC3-HDL also shows positive correlation with the morbidly obese phenotype. However, the roles of APOC3 in HDL functionality and adipose tissue metabolic activity remain unknown. Therefore, here we investigated the direct effects of APOC3 expression on HDL structure and function, as well as white adipose tissue (WAT) and brown adipose tissue (BAT) metabolic activity. C57BL/6 mice were infected with an adenovirus expressing human APOC3 or a recombinant attenuated control adenovirus expressing green fluorescent protein and blood and tissue samples were collected at 5 days postinfection. HDL was then analyzed for its apolipoprotein and lipid composition and particle functionality. Additionally, purified mitochondria from BAT and WAT were analyzed for uncoupling protein 1, cytochrome c (Cytc), and Cytc oxidase subunit 4 protein levels as an indirect measure of their metabolic activity. Serum metabolomic analysis was performed by NMR. Combined, our data show that APOC3 modulates HDL structure and function, while it selectively promotes BAT metabolic activation.

Glucose metabolism of visceral adipose tissue measured by 18F-FDG PET/CT is related to the presence of colonic adenoma.

This study investigated the relationships between the area and metabolic activity of adipose tissue and the presence of colorectal adenoma (CRA). Our institutional review board approved the study and waived informed consent. A total of 212 subjects who underwent fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) and colonoscopy for routine health check-ups were enrolled. The volumetric parameters of areas of visceral (VATav), subcutaneous (SATav), and total adipose tissue (TATav) and calculated visceral-to-subcutaneous adipose tissue ratio (VSR) and visceral-to-total adipose tissue ratio (VAR) were considered. Metabolic parameters of standardized uptake value (SUV) of visceral (vcSUVmax, vcSUVmean), subcutaneous (scSUVmax, scSUVmean), and calculated visceral-to-subcutaneous adipose tissue ratio (VSRmax, VSRmean) were considered. Anthropometric data of height, weight, body mass index (BMI), waist circumference (WC), body fat mass (BFM), skeletal muscle mass (SMM), and diverse laboratory data were also considered as variables. Sixty-six subjects were placed in the CRA group and 146 subjects in the non-CRA group. The presence of CRA was significantly correlated with older age (P = .001), male sex (P = .041), higher BMI (P = .004), higher WC (P = .001), higher BFM (P = .024), higher VATav (P < .001), higher TATav (P = .004), higher VSR (P < .001), higher VAR (P < .001), lower vcSUVmax (P = .002), lower vcSUVmean (P < .001), and lower VSRmean (P = .002). On multiple regression analysis, vcSUVmax and vcSUVmean were independently associated with the presence of CRA (P = .009 and P = .045). Lower glucose metabolism of visceral adipose tissue was related to the presence of CRA. Our findings identify the value of visceral metabolic dysfunction as a potential surrogate marker of elevated risk for CRA.

Different adipose tissue depots: Metabolic implications and effects of surgical removal

Increased adiposity has been associated to worse metabolic profile, cardiovascular disease, and mortality. There are two main adipose tissue depots in the body, subcutaneous and visceral adipose tissue, which differ in anatomical location. A large body of evidence has shown the metabolic activity of adipose tissue; lipectomy and/or liposuction therefore appear to be alternatives for improving metabolic profile through rapid loss of adipose tissue. However, surgical removal of adipose tissue may be detrimental for metabolism, because subcutaneous adipose tissue has not been associated to metabolic disorders such as insulin resistance and type 2 diabetes mellitus. In addition, animal studies have shown a compensatory growth of adipose tissue in response to lipectomy. This review summarizes the implications of obesity-induced metabolic dysfunction, its relationship with the different adipose tissue depots, and the effects of lipectomy on cardiometabolic risk factors.

MR blockade protects against diet induced obesity, adipocyte dysfunction and cardiac inflammation in mice, through browning of the adipose organ and modulation of autophagy

Obesity is a key factor in the development of insulin resistance (IR), cardiovascular disease, hypertension, type 2 diabetes etc. Given the near epidemic incidence of obesity in western society there is a clear need for effective treatment options. Mineralocorticoid receptor (MR) blockade has shown significant promise in transgenic mouse models of obesity in limiting IR and adipocyte dysfunction, a disease that is independent of classical MR actions (renal). Female 10-weekold C57bl6 mice were fed with normal chow or a high fat (HF) diet for 12 weeks. Mice fed HF diet were concomitantly treated for 12 weeks with drospirenone (DRSP, 6 mg/kg/day), a potent MR antagonist with antiadipogenic activity, or spironolactone (SPIRO, 20 mg/kg/day). Mice fed HF diet showed a significant increase in total body weight, fat mass, mean adipocyte size, expression of white adipose tissue (WAT) marker genes and showed impaired glucose tolerance after intraperitoneal plasma glucose tolerance test. DRSP and SPIRO prevented weight gain and white fat mass expansion induced by HF diet in parametrial, perivescical, and inguinal depots without affecting interscapular fat pad weight. Magnetic Resonance Imaging (MRI) confirmed that MR antagonists blocked the HF dietdriven expansion of abdomino-pelvic (parametrial and perivescical) fat volume. High levels of MR mRNA were detected in all depots of adipose tissue. HF fed mice showed no increase in heart or kidney weight and tissue fibrosis. Cardiac macrophage recruitment and osteopontin staining was increased in hearts of HF fed mice and reversed by both MR antagonists. Moreover, both DRSP and SPIRO prevented the impaired glucose tolerance in mice fed HF diet, and countered HF diet-induced up-regulation of WAT markers transcripts and adipocyte hypertrophy. Importantly, MR antagonists increased uncoupling protein 1 (UCP-1) positive brown-like adipocyte content in WAT, and improved metabolic activity of adipose tissue, as indicated by PET/CT imaging. In keeping with this, MR antagonism significantly increased expression of brown-like adipocyte marker genes such PRDM16, CIDEA, beta-3 adrenergic receptor (ADRB3) and UCP-1 in all WAT depots analysed. In exploring the mechanism, we demonstrated that MR antagonism induced brown adipose tissue (BAT) markers, and reduced the autophagic rate, a key remodelling process in adipocyte differentiation, in WAT depots in vivo as well as in primary cultured adipocytes. We conclude that adipocyte MR regulates BAT-like remodeling of WAT through modulation of autophagy. MR blockade therefore has promise as a novel therapeutic option for the prevention of metabolic dysfunctions and the cardiac consequences of obesity. doi:10.1016/j.ijcme.2015.05.012 Transcriptional control of ICAM-1 in human coronary artery endothelial cells by Mineralocorticoid Receptor (MR): Implications for the protective effects of MR antagonists in cardiovascular diseases V. Marzolla, A. Armani, A. Fabbri, I.Z. Jaffe, M. Caprio Laboratory of Cardiovascular Endocrinology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Pisana, Rome, Italy Department of Medicina dei Sistemi, Endocrinology Unit, S. Eugenio & CTO A. Alesini Hospitals, University Tor Vergata, Rome, Italy Molecular Cardiology Research Institute, Tufts Medical Center, Boston,