Visceral Adipose Tissue Mass Research Articles

Evaluation of the Severity of Hyperlipidemia Pancreatitis Using CT-measured Visceral Adipose Tissue.

Computed tomography-measured visceral adipose tissue (VAT) and the distribution of VAT are highly correlated with the severity and prognosis of acute pancreatitis (AP). To date, all available data are from the overall AP patient population; no subgroup analysis has been conducted to evaluate patients with moderately severe AP or patients with hyperlipidemia acute pancreatitis (HLAP) as independent populations. Currently, studies on the relationship between VAT and HLAP are lacking. A total of 235 patients with moderately severe AP or severe acute pancreatitis were divided into 2 groups according to whether hyperlipidemia was present: the HLAP group and the non-HLAP group. The general inpatient information was collected, and computed tomography was used to measure VAT, subcutaneous adipose tissue (SAT), total adipose tissue, and VAT/SAT (V/S). The data were subjected to t test, χ test, matrix scatter plot, logistic regression, and receiver operating characteristic analyses to evaluate the relationship between VAT and HLAP severity. Significant differences were observed in VAT, SAT, total adipose tissue, and triglycerides (TGs) between the HLAP group and the non-HLAP group (P<0.001). Significant correlations were observed between VAT and body mass index (r=0.425, P=0.017) and between VAT and TG (r=0.367, P=0.042). In the HLAP group, VAT, V/S, TG, and local complications may have significant effects on disease severity. The receiver operating characteristic curves showed that VAT and V/S were more reliable than TGs in evaluating disease severity [area under the curve (AUC) of VAT: 0.819, P<0.001; AUC of V/S: 0.855, P<0.001; AUC of TG: 0.671, P=0.04]. Disease severity was reliably evaluated at 139 cm, the cut-off value of VAT. The cut-off value of V/S was 1.145; high V/S was associated with extended intensive care unit stay. VAT and its distribution had no significant effects on mortality. For patients with moderately severe to severe HLAP, VAT was correlated with body mass index and TG. VAT and V/S were valuable factors for evaluating disease severity and prognosis. However, VAT had no effect on mortality, and VAT could not be used to evaluate patients with moderately severe to severe non-HLAP.

Maternal Genistein Intake Mitigates the Deleterious Effects of High-Fat Diet on Glucose and Lipid Metabolism and Modulates Gut Microbiota in Adult Life of Male Mice.

Adverse early-life exposures program increased risk of chronic metabolic diseases in adulthood. However, the effects of genistein supplementation in early life on metabolic health in later life are largely unclear. Our objective was to investigate whether maternal genistein intake could mitigate the deleterious influence of a maternal high-fat diet on glucose and lipid metabolism in offspring and to explore the role of gut microbiota in mediating the transgenerational effects. C57BL/6 female mice were fed either a high-fat diet (HF), high-fat diet with genistein (0.6 g/kg diet) (HFG) or normal control diet (C) for 3 weeks before pregnancy and throughout pregnancy and lactation. The male offspring had ad libitum access to normal chow diet from weaning to 24 weeks of age. Then the content of inguinal subcutaneous adipose tissue (SAT) and epididymal visceral adipose tissue (VAT) were weighed. Glucose tolerance test (GTT), the level of serum insulin and lipid profiles were analyzed. The caecal contents were collected for 16S rDNA sequencing. The results showed that maternal genistein intake could significantly reduce blood glucose levels during GTT, fasting insulin levels, VAT mass and serum triglyceride levels as well as increase high-density lipoprotein cholesterol in adult male offspring. Significant decrease of germs from the Tenericutes phylum and enrichment of Rikenella as well as SCFA (short-chain fatty acid)-producing bacteria, including Alloprevotella, Odoribacter, and Clostridium XlVa, in offspring of genistein fed dams might play crucial roles in the improvement of glucose and lipid metabolism. Overall, early-life genistein intake attenuated the harmful effects of maternal HF on metabolism in adult offspring and the protective effects were associated with the alterations in gut microbiota, which provides new evidence and targets for mitigate the poor effects of adverse early-life exposures on metabolic health in later life.

Immune-Deficient Pfp/Rag2−/− Mice Featured Higher Adipose Tissue Mass and Liver Lipid Accumulation with Growing Age than Wildtype C57BL/6N Mice

Aging is a risk factor for adipose tissue dysfunction, which is associated with inflammatory innate immune mechanisms. Since the adipose tissue/liver axis contributes to hepatosteatosis, we sought to determine age-related adipose tissue dysfunction in the context of the activation of the innate immune system fostering fatty liver phenotypes. Using wildtype and immune-deficient mice, we compared visceral adipose tissue and liver mass as well as hepatic lipid storage in young (ca. 14 weeks) and adult (ca. 30 weeks) mice. Adipocyte size was determined as an indicator of adipocyte function and liver steatosis was quantified by hepatic lipid content. Further, lipid storage was investigated under normal and steatosis-inducing culture conditions in isolated hepatocytes. The physiological age-related increase in body weight was associated with a disproportionate increase in adipose tissue mass in immune-deficient mice, which coincided with higher triglyceride storage in the liver. Lipid storage was similar in isolated hepatocytes from wildtype and immune-deficient mice under normal culture conditions but was significantly higher in immune-deficient than in wildtype hepatocytes under steatosis-inducing culture conditions. Immune-deficient mice also displayed increased inflammatory, adipogenic, and lipogenic markers in serum and adipose tissue. Thus, the age-related increase in body weight coincided with an increase in adipose tissue mass and hepatic steatosis. In association with a (pro-)inflammatory milieu, aging thus promotes hepatosteatosis, especially in immune-deficient mice.

Interaction Among Sex, Aging, and Epigenetic Processes Concerning Visceral Fat, Insulin Resistance, and Dyslipidaemia.

The distribution of adipose tissue is influenced by gender and by age, shifting from subcutaneous to visceral depots with longevity, increasing the development of several aging-related diseases and manifestations such as obesity, metabolic syndrome, and insulin resistance. Epigenetics might have an important role in aging processes. The aim of this research was to investigate the interactions between aging and epigenetic processes and the role of visceral adipose tissue, insulin resistance, and dyslipidaemia. Two different study samples of 366 and 269 adult participants were analyzed. Anthropometric, biochemical (including the triglycerides-glucose (TyG) index), and blood pressure measurements were assessed following standardized methods. Body composition measurements by Dual-energy X-ray absorptiometry (DXA) were also performed for the second sample. Methylation data were assessed by Infinium Human Methylation BeadChip (Illumina) in peripheral white blood cells. Epigenetic age acceleration was calculated using the methods DNAmAge (AgeAcc) and GrimAge (AgeAccGrim). Age acceleration (AgeAccGrim) showed better correlations than AgeAcc with most of the measured variables (waist circumference, glucose, HOMA-IR, HDL-cholesterol, triglycerides, and TyG index) for the first sample. In the second sample, all the previous correlations were confirmed, except for HOMA-IR. In addition, many of the anthropometrical measurements assessed by DXA and C-reactive protein (CRP) were also statistically associated with AgeAccGrim. Associations separated by sex showed statistically significant correlations between AgeAccGrim and HDL-cholesterol or CRP in women, whereas, in men, the association was with visceral adipose tissue mass DXA, triglycerides and TyG index. Linear regression models (model 1 included visceral adipose tissue mass DXA and TyG index and model 2 included HDL-cholesterol and CRP) showed a significant association for men concerning visceral adipose tissue mass DXA and TyG index, while HDL-cholesterol and CRP were associated in women. Moreover, structural equation modeling showed that the TyG index was mediating the majority of the visceral adipose tissue mass action on age acceleration. Collectively, these findings showed that there are different mechanisms affecting epigenetic age acceleration depending on sex. The identified relationships between epigenetic age acceleration and disease markers will contribute to the understanding of the development of age-related diseases.

Dietary fiber content affects growth, body composition, and feed intake and their associations with a major growth locus in growing male chickens of an advanced intercross population

In this study, we examined the effect of different dietary fiber concentrations on growth, body composition, and feed efficiency of growing male chickens with different genetic background. We tested whether the single nucleotide polymorphisms (SNP) in a previously identified growth locus on chromosome 4 (GGA4) between 69.3 and 77.9 Mb was associated with the traits of biologic and commercial importance in interaction with the diet. The study was conducted with growing male chickens of generation 12 of an advanced intercross population descending from the initial cross between inbred New Hampshire (high-growth) and White Leghorn (low-growth) lines. We performed a 2-way interaction analysis between the dietary fiber content and SNP genotypes. At wk 4, the growing male chickens were randomly divided into 2 diet treatments, which were housed and fed individually with either a low- (LFD, n = 38) or a high-fiber diet (HFD, n = 41) containing 0.8 and 5% lignocellulose with a crude fiber content of 60%, respectively. Body weights were recorded weekly. Body composition was examined at wk 13. Feed intake and excreta were analyzed at wk 6 and 13. The effect of dietary fiber content on body weight gain and feed intake was age-dependent. The feed conversion ratio was not altered. Feeding HFD resulted in 10% greater body weight gain (P = 0.047) and greater feed intake (P = 0.014) than LFD at wk 6. At wk 13, the visceral adipose tissue mass was 38% lower (P = 0.008) and the gizzard mass was 14% greater (P = 0.012). The reduction of total fat content in adipose tissue (P = 0.039) in the HFD was associated with reduced intramuscular fat content in drumsticks-thighs (4.2 vs. 5.1%, P = 0.004). The SNP genotypes at the GGA4 locus interacted with dietary fiber content and influenced body weight gain (P = 0.042), visceral adipose tissue mass (P ≤ 0.029), and feed intake (P ≤ 0.050). The New Hampshire alleles of SNPs on GGA4 led to increased body weight gain and feed intake (P ≤ 0.050), and tended to reduced fat deposition under HFD. Our data indicate that the addition of lignocellulose to the diet would improve productivity and carcass quality through reduced adipose tissue mass without changes in feed efficiency. Furthermore, our findings provide evidence for interaction of the target GGA4 region with dietary fiber usage affecting growth, fat deposition, and feed intake. The particular GGA4 locus may contain a single or several genes associated with growth, body composition, and feed intake.

Evaluation of Preoperative Abdominal Adipose Tissue–, Inflammation-, Muscle Mass–, and Nutritional Status–based Prognostic Markers to Assess Renal Dysfunction in Living Kidney Donors

BackgroundLiving kidney donors (LKDs) are at high risk of renal dysfunction after undergoing a donor nephrectomy (DN), resulting in poor prognosis associated with the development of cardiovascular or cerebrovascular disease. Decreasing this risk can improve the survival rate of LKDs. We investigated the effects of preoperative conditions in LKDs on renal dysfunction after DN using abdominal adipose tissue, inflammation, nutritional status, and muscle mass as markers for this assessment. MethodsOur retrospective study included 79 LKDs. Body composition markers were assessed using preoperative unenhanced computed tomographic images. Inflammation- and nutritional status–based markers were assessed using preoperative laboratory blood tests. The association between each marker was investigated, and prognostic markers for renal dysfunction after DN were identified. ResultsThe LKDs in this cohort comprised 30 men and 49 women. The median age at the time of DN and the preoperative estimated glomerular filtration rate were 58 years and 81.9 mL/min/1.73 m2, respectively. Abdominal subcutaneous adipose tissue and muscle mass significantly differed between the sexes. Each adipose tissue–, inflammation-, nutritional status–, and muscle mass–based marker showed an association with each other. Abdominal visceral adipose tissue and nutritional status could be independent prognostic markers for renal dysfunction after DN. ConclusionsOur findings suggest that the preoperative condition of LKDs (assessed using specific markers such as abdominal visceral adipose tissue mass per volume and nutritional status) could affect renal dysfunction after DN. Optimal preoperative management can lead to better outcomes in LKDs. Further research is needed to establish appropriate exercise programs and nutritional interventions.

Cardiopulmonary fitness but not muscular fitness associated with visceral adipose tissue mass

Purpose The purpose of this study is to identify the association between physical fitness (cardiopulmonary and musculoskeletal) and the distribution of abdominal fat in overweight and obese adults. Methods Of the total 102 overweight and obese participants, 99 participants completed all measurements. Cardiopulmonary fitness was assessed by maximal oxygen consumption test and muscular fitness was assessed using 10 repetition max. Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were assessed by computed tomography (CT) at the level of lumbar spine 4–5. Results Cardiopulmonary fitness was inversely associated with both VAT and SAT, while muscular fitness only inversely associated with SAT. Multiple linear regression analyses indicated that gender, age, and cardiopulmonary fitness, but not muscular fitness, were associated with VAT, and age, cardiopulmonary fitness, and muscular fitness were significantly associated with SAT. Conclusions Cardiopulmonary fitness is more closely related to both VAT and SAT while muscular fitness is related with SAT.

Effects of Intermittent Energy Restriction Combined with a Mediterranean Diet on Reducing Visceral Adiposity: A Randomized Active Comparator Pilot Study.

Intermittent energy restriction combined with a Mediterranean diet (IER+MED) has shown promise to reduce body fat and insulin resistance. In the Multiethnic Cohort Adiposity Phenotype Study, Japanese Americans had the highest visceral adipose tissue (VAT) when adjusting for total adiposity. We conducted this pilot study to demonstrate feasibility and explore efficacy of following IER+MED for 12 weeks to reduce VAT among East Asians in Hawaii. Sixty volunteers (aged 35–55, BMI 25–40 kg/m2, VAT ≥ 90 cm2 for men and ≥ 80 cm2 for women) were randomized to IER+MED (two consecutive days with 70% energy restriction and 5 days euenergetic MED) or an active comparator (euenergetic Dietary Approaches to Stop Hypertension (DASH) diet). Participants and clinic staff (except dietitians) were blinded to group assignments. IER+MED had significantly larger reductions in DXA-measured VAT and total fat mass (−22.6 ± 3.6 cm2 and −3.3 ± 0.4 kg, respectively) vs. DASH (−10.7 ± 3.5 cm2 and −1.6 ± 0.4 kg) (p = 0.02 and p = 0.005). However, after adjusting for total fat mass, change in VAT was not statistically different between groups; whereas, improvement in alanine transaminase remained significantly greater for IER+MED vs. DASH (−16.2 ± 3.8 U/L vs. −4.0 ± 3.6 U/L, respectively, p = 0.02). Attrition rate was 10%, and participants adhered well to study prescriptions with no reported major adverse effect. Results demonstrate IER+MED is acceptable, lowers visceral and total adiposity among East Asian Americans, and may improve liver function more effectively than a healthful diet pattern. ClinicalTrials.gov Identifier: NCT03639350.

Age- and sex-specific reference intervals for visceral fat mass in adults.

Dual-energy X-ray absorptiometry (DXA) is becoming a method of choice for the assessment of visceral adipose tissue (VAT) but the lack of robust reference ranges presents a challenge to the interpretation of VAT in clinical practice, research settings, and the athletic environment. The objective of this study was to develop age- and sex-specific reference intervals for DXA-derived VAT mass. The reference group comprised 3219 adults (1886 general population, 42% women; 1333 athletes, 11% women) in the United Kingdom, aged 18-83 years. Total body scans were performed using a GE Lunar iDXA and VAT analyses were enabled through Corescan software (Encore version 15.0). Age-specific reference ranges were derived in samples stratified by sex and general population/ athlete status. We modelled the mean and SD of Box-Cox transformed VAT mass as a function of age with a generalised least squares method using fractional polynomials (Stata® -xrigls- program). Centile values were then back-transformed to provide reference intervals on the original scale. In general population samples, average VAT mass increases with age up until around 65-70 years, and then begins to decline at older ages, though data are relatively sparse at the upper end of the age range. In athletes, on average, VAT mass increases with advancing age in men and women. Both 95 and 98% reference ranges are presented in 5-year increments in all samples, and we provide equations to enable the calculation of any centile, for any age within the range. These reference data can aid the interpretation of VAT mass specific to an individual's sex, age, and athletic status, increasing the utility and applicability of DXA-derived VAT assessments. Additional research is needed in adults over 65 years and female athletes, with different DXA devices, across different ethnic groups and specific sports.

PB1846 ANTHROPOMETRIC AND HORMONAL PARAMETERS IN COMPARISON WITH BONE MINERAL DENSITY IN MEN WITH HAEMOPHILIA FROM LOWER SILESIA ‐ PRELIMINARY REPORT

Background:In patients with haemophilia, recurrent episodes of bleeding lead to joint deterioration and bone resorption. To date, the effect of various risk factors on the bone mineral density (BMD) reduction have found conflicting results.Aims:The aim of the study was to analyze the impact of certain parameters, such as: viral status of patients, estradiol, testosteron, parathormone and vitamin D levels in relation to bone density.Methods:24 men with moderate and severe haemophilia, aged 18‐35 were enrolled. BMD at the lumbar spine, trabecular bone score (TBS) and total body densitometry were measured using dual X ray absorptiometry method (DXA) (densitometer Horizon, Hologic, 2017). Blood analyses were performed for morphology parameters, liver and kidney function parameters, HCV, HBV, HIV viral status, estradiol, testosteron, DHEA‐S, TSH, parathormone and Vitamin D levels.Results:The study population included 24 men with haemophilia A, who had been receiving prophylactic factor replacement therapy. HCV seropositivity was found in 6/24 patients (25%), whereas HBV seropositivity was detected in 4 patients (16,7%). There was no patient infected with HIV virus. No statistical correlation was found between BMD and viral serological status. It was found that in 15/24 patients BMD was normal with a Z‐score of &gt; ‐1 (62,5%), whereas in 9/24 patients (37,55%), BMD was decreased. In hemophilic patients with normal BMD Z‐score, the increased BMI, androidal fat deposit (AFD), gynoidal fat deposit (GFD), fat mass index (FMI), free fat mass index (FFMI), Estimated visceral adipose tissue (Est VAT) mass were detected. Among all analyzed hormones, only serum estradiol concentration was statistically higher in patients with normal BMD. In 17/24 examined patients Vitamin D deficiency (&lt;20 ng/ml) was detected (71%), although Vitamin D insufficiency (&lt;30 ng/ml) was found in 4/24 patients (16,7%). Three patients (12,5%) had a normal Vitamin D concentration.Summary/Conclusion:The higher BMD in haemophilic patients is related with certain anthropometric parameters, such as body‐fat‐, free‐fat‐mass indexes and visceral fat tissue. BMD negatively correlated with % body fat, androidal fat mass and PTH, whereas TBS negatively related with androidal/visceral fat mass. We found that Vitamin D deficiency is very common in haemophilic patients, however there was no correlation between Vitamin D levels and BMD.

Metformin monotherapy significantly decreases epicardial adipose tissue thickness in newly diagnosed type 2 diabetes patients

IntroductionImbalance between pro- and anti-inflammatory cytokines secreted from visceral adipose tissue (VAT) contributes to the pathogenesis of certain cardiovascular and metabolic disorders, including insulin resistance. Epicardial adipose tissue (EAT) is a form of VAT mainly concentrated along the coronary arteries. It has been shown in various studies that EAT thickness is positively correlated with cardiovascular disease. Due to its high worldwide prevalence, prevention and management of type 2 diabetes (T2D) has become a major public health challenge. Metformin, the most widely prescribed drug to treat T2D, has favorable effects on VAT and body weight. As metformin decreases VAT mass, in this prospective study we analyzed the possible positive effect of metformin on EAT mass, which is organ-specific VAT, and body mass index (BMI). MethodsSubjects were selected from patients admitted to the internal medicine outpatient clinic. Newly diagnosed T2D patients treated with metformin monotherapy were analyzed and 40 patients were included. EAT thickness in the included patients was measured echocardiographically. BMI and EAT thickness were analyzed at the beginning (BMI0 and EAT0) and after three months of metformin monotherapy (BMI3 and EAT3). ResultsThere was a statistically significant decrease in EAT thickness after three months of metformin monotherapy (EAT0=5.07±1.33 mm vs. EAT3=4.76±1.32 mm; p<0.001). Furthermore, BMI was also significantly decreased (BMI0=28.27±2.71 vs. BMI3=27.29±2.10; p<0.0001). ConclusionsIn this study we show that metformin monotherapy significantly decreases EAT thickness and BMI in T2D patients. This suggests that metformin could reduce the frequency of coronary atherosclerosis.

Risk Factors for Low Muscle Mass in a Population-based Prospective Cohort of Brazilian Community-dwelling Older Women: The São Paulo Ageing & Health (SPAH) Study

Introduction: Sarcopenia is characterized by progressive loss of skeletal muscle mass, which results in decreased muscle strength, functional impairment, and increased risk of death. Few studies have performed a concomitant evaluation of clinical, laboratory, and body composition variables to accurately determine the contribution of each parameter to low muscle mass (LMM) in older subjects. This study aimed to identify risk factors (clinical, laboratory parameters, BMD, and body composition by DXA including visceral fat) for LMM in a prospective cohort of older Brazilian women. Methods: A total of 408 women aged ≥65 yr from the São Paulo Ageing & Health study were evaluated with clinical data, laboratory bone tests, BMD, and body composition by DXA using Hologic QDR 4500A equipment. Risk factors were measured at baseline (2005–2007). After a follow-up of 4.3 ± 0.8 yr, subjects were classified according to the LMM definition of the Foundation for the National Institutes of Health criteria. LMM was defined when appendicular lean mass divided by body mass index was less than 0.512. Multivariate logistic regression models were used to identify independent risk factors for LMM. Results: At the end of follow-up, 116 women (28.4%) had LMM. Age averages were 73.3 ± 4.9 yr in the LMM group and 72.5 ± 4.5 yr in the normal group (p = 0.11). Mean BMI was 30.6 ± 5.2 kg/m2 in the LMM group and 28.1 ± 4.7 kg/m2 in the normal group (p < 0.001). In multivariate analyses, predictors of LMM were: falls (OR = 1.14, p = 0.016), TSH levels (OR = 1.08, p = 0.018, per 1 μUI/L-increase), serum creatinine levels (OR = 11.11, p < 0.001, per 1 mg/dL-decrease), and visceral adipose tissue (VAT) mass (OR = 1.17, p < 0.001, per 100 g increase). Conclusions: Falls, high TSH, low creatinine, and high VAT were risk factors for LMM in older women. More attention should be paid to these factors, since they are potentially reversible with adequate intervention.

Total and Regional Body Composition of NCAA Division I Collegiate Baseball Athletes.

This study's purpose was to evaluate total, regional, and throwing versus non-throwing arm body composition measurements between various positions of NCAA Division I male baseball players using dual X-ray absorptiometry (DXA). Two hundred and one collegiate baseball athletes were measured using DXA. Visceral adipose tissue (VAT), total and regional fat mass (FM), lean mass (LM), and bone mineral density (BMD) were measured. Athletes were separated into: pitchers (n=92), catchers (n=25), outfielders (n=43), and infielders (n=41). ANOVA and Tukey's honest significant difference assessed total and regional differences between positions. Infielders had significantly (p<0.05) lower total LM than pitchers and outfielders. Additionally, outfielders had significantly lower total FM compared to pitchers and catchers. No significant differences between positions were observed for total BMD and VAT. Pitchers' and infielders' throwing arm demonstrated significantly greater total mass, FM, LM, and BMD compared to the non-throwing arm. Further, outfielders' throwing arm total mass, LM, and BMD were significantly higher vs. the non-throwing arm. Significant differences were observed in total and regional body composition measurements across position, in addition to differences in throwing arm vs. non-throwing arm composition. These measurement values are important to coaches and trainers as normative positional DXA data for collegiate baseball players.

MON-474 Dipeptidyl Peptidase-4 (DPP4) Inhibition Decreases Visceral Fat and Improves Glucose Metabolism in Overweight Women with Polycystic Ovarian Syndrome

Background: Women with PCOS have decreased GH secretion.1 Diminished GH is associated with increased visceral adiposity and impaired vascular function. GH releasing hormone is the primary stimulus for GH secretion and a substrate of dipeptidyl peptidase-4 (DPP4).2 We tested the hypothesis that one month of DPP4 inhibition with sitagliptin increases GH secretion and improves glucose metabolism and vascular function in women with PCOS. Methods: Eighteen women with PCOS (BMI ≥ 25 kg/m2) participated in a randomized, double-blinded, cross-over study during which they received sitagliptin 100 mg p.o. vs. placebo daily for one month separated by a minimum eight-week wash-out. At two weeks, women underwent a 75 g oral glucose tolerance test (OGTT). At one month, women were admitted for fasting laboratories, assessment of conduit artery vascular function, and measurement of body composition via DEXA. Overnight GH secretion was assessed using an automated deconvolution algorithm (AutoDecon) previously validated for the analysis of endogenous pulsatile GH secretion from time-series data obtained via frequent venous sampling from an indwelling catheter every ten minutes for twelve hours. Results: Sitagliptin 100 mg daily decreased DPP4 activity (p<0.001 vs. placebo) and increased GLP-1 levels (p<0.001 vs. placebo) during OGTT. Glucose metabolism improved during sitagliptin, as demonstrated by mean decrease in blood glucose of 15.4 mg/dL (95% CI 8.7, 22.1; p<0.001) at 100 minutes as compared to placebo. Sitagliptin enhanced early insulin secretion (from mean insulinogenic index 1.9 ± SD 1.2 to 3.2 ± 3.1; p=0.01). At one month, sitagliptin decreased visceral adipose tissue (VAT) (from 1141.9 g ± 700.7 to 1055.1 ± 710.1; p=0.02) and total cholesterol (from 168.8 mg/dL ± 26.3 to 162.5 ± 22.2; p=0.02) but did not affect vascular function. Sitagliptin did not increase overnight GH secretion, as summarized by area over the curve (AUC) or mean GH, but did increase GH half-life (from 13.9 min ± 3.6 to 16.8 ± 6.2, N=16; p=0.04) and the interpulse interval (from 53.2 min ± 20.0 to 77.3 ± 38.4, N=16; p<0.05). DPP4 activity levels during sitagliptin were associated with overnight GH secretion (GH AUC: rs= -0.60, p=0.01; mean GH: rs= -0.57, p=0.02), VAT mass (rs= 0.66; p<0.01), and insulin resistance (HOMA-IR rs=0.54; p=0.04). Conclusions: Sitagliptin improved blood glucoses following 75 g OGTT in overweight women with PCOS and decreased VAT but did not enhance vascular function. While sitagliptin did not increase overnight GH secretion, it did enhance GH half-life and the interpulse interval. Moreover, the response to sitagliptin was directly related to overnight GH secretion and inversely to VAT and insulin resistance. In this pilot study, sitagliptin improved glucose metabolism and body composition in accordance with GH secretion. 1 deBoer et al., Hum. Reprod. 2004 19: 504. 2 Frohman et al., J Clin Invest. 1986 78:906.

Precision of the Hologic DXA in the Assessment of Visceral Adipose Tissue

Introduction: Visceral fat, also known as visceral adipose tissue (VAT), has been the focus of intensive research over the past several yr, as ground breaking studies have investigated its possible role in predicting long-term cardiac dysfunction, hypertension, and diabetes. Historically, magnetic resonance imaging and computed tomography were the instruments of choice for visceral fat quantification. However, with the introduction of visceral fat assessment software for Dual-energy X-ray Absorptiometry (DXA) scanners, DXA's use for VAT assessment has become increasingly common. To effectively utilize DXA in future VAT research studies, information about their precision and accuracy must be known. This study provides novel information regarding the precision of the Hologic Horizon DXA scanner in the assessment of VAT. Methods: Sixty individuals (32.7 ± 17.1 yr, 51% male, 40% with body mass index (BMI) > 25 kg/m2) above the age of 16 years were recruited to participate in this study. Subjects found to be pregnant, have a lumbar vertebral compression fracture, nonremovable metal implants in the abdomen, or scoliosis/lordosis/kyphosis were excluded from the study. All subjects underwent 3 consecutive whole body scans on a Hologic Horizon A DXA scanner. Results: VAT mass ranged from 102 g to 1454 g. VAT precision improved with increasing BMI (p = 0.025): coefficient of variation (%CV) was 15.2% for underweight subjects (n = 2), 7.1% for healthy subjects (n = 34), 6.4% for overweight subjects (n = 18), and 4.7% for obese subjects (n = 6). Conclusions: VAT measurement by Hologic DXA displays a satisfactory level of precision in individuals with a BMI of >18.5 kg/m2. Precision was found to be higher in those with the greatest risk of cardio-metabolic dysfunction (individuals with high VAT). Due to its low cost, brief examination time, noninvasiveness, and limited radiation exposure, DXA may be considered the tool of choice for VAT determination in future studies.

Quantitative bias analysis of the association of type 2 diabetes mellitus with 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB-153)

An association between serum concentrations of persistent organic pollutants (POPs), such as 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB-153), and risk of type 2 diabetes mellitus (T2DM) has been reported. Conditional on body mass index (BMI) and waist circumference (WC), a higher serum PCB-153 concentration may be a marker of T2DM risk because it reflects other aspects of obesity that are related to T2DM risk and to PCB-153 clearance. To estimate the amount of residual confounding by other aspects of obesity, we performed a quantitative bias analysis on the results of a specific study. A physiologically-based pharmacokinetic (PBPK) model was developed to predict serum levels of PCB-153 for a simulated population. T2DM status was assigned to simulated subjects based on age, sex, BMI, WC, and visceral adipose tissue mass. The distributions of age, BMI, WC, and T2DM prevalence of the simulated population were tailored to closely match the target population. Analysis of the simulated data showed that a small part of the observed association appeared to be due to residual confounding. For example, the predicted odds ratio of T2DM that would have been obtained had the results been adjusted for visceral adipose tissue mass, for the ≥90th percentile of PCB-153 serum concentration, was 6.60 (95% CI 2.46–17.74), compared with an observed odds ratio of 7.13 (95% CI 2.65–19.13). Our results predict that the association between PCB-153 and risk of type 2 diabetes mellitus would not be substantially changed by additional adjustment for visceral adipose tissue mass in epidemiologic analyses. Confirmation of these predictions with longitudinal data would be reassuring.

Dietary Niacin Intake Predicts the Decrease of Liver Fat Content During a Lifestyle Intervention

Niacin inhibits fatty acid flux from adipose tissue to liver, reduces hepatic triglyceride synthesis and increases hepatic lipid oxidation. Thus, niacin may have a role in the regulation of liver fat content in humans. We tested if dietary intake of niacin predicts change of liver fat content during a lifestyle intervention. To this end, we estimated the composition of diet from diaries of 202 healthy subjects at risk of type 2 diabetes undergoing lifestyle intervention comprising physical activity and diet counselling. Total-, subcutaneous- and visceral adipose tissue mass were measured by magnetic resonance (MR) tomography and liver fat content by 1H-MR spectroscopy at baseline and after 9 months of follow-up. Among fat compartments, liver fat content showed the largest decrease (−32%, p < 0.0001). High baseline niacin intake predicted a larger decrease of liver fat (p = 0.004). Subjects in the highest quartile of niacin intake at baseline also had the largest decrease of liver fat (1st:−10%; 2nd:−27%; 3rd:−35%; 4th:−37%). Among 58 subjects with nonalcoholic fatty liver disease (NAFLD) at baseline, NAFLD resolved in 23 subjects during the lifestyle intervention. For one standard deviation increase in niacin intake, the odds ratio for resolution of NAFLD was 1.77 (95% CI, 1.00–3.43). High dietary niacin intake may have a favorable effect on the reduction of liver fat during lifestyle intervention.

Reduction of visceral adipose tissue mass requires IL-6 signalling

Reduction of visceral adipose tissue mass requires IL-6 signalling

A Polygenic Risk Score of Lipolysis-Increasing Alleles Determines Visceral Fat Mass and Proinsulin Conversion.

Primary dysregulation of adipose tissue lipolysis caused by genetic variation and independent of insulin resistance could explain unhealthy body fat distribution and its metabolic consequences. To analyze common single nucleotide polymorphisms (SNPs) in 48 lipolysis-, but not insulin-signaling-related genes, to form polygenic risk scores of lipolysis-associated SNPs, and to investigate their effects on body fat distribution, glycemia, insulin sensitivity, insulin secretion, and proinsulin conversion. SNP array, anthropometric, and metabolic data were available from up to 2789 participants without diabetes of the Tübingen Family study of type 2 diabetes characterized by oral glucose tolerance tests. In a subgroup (n = 942), magnetic resonance measurements of body fat stores were available. We identified insulin-sensitivity-independent nominal associations (P < 0.05) of SNPs in 10 genes with plasma free fatty acids (FFAs), in 7 genes with plasma glycerol and in 6 genes with both, plasma FFAs and glycerol. A score formed of the latter SNPs (in ADCY4, CIDEA, GNAS, PDE8B, PRKAA1, PRKAG2) was associated with plasma FFA and glycerol measurements (1.4*10-9 ≤ P ≤ 1.2*10-5), visceral adipose tissue mass (P = 0.0326), and proinsulin conversion (P ≤ 0.0272). The more lipolysis-increasing alleles a subject had, the lower was the visceral fat mass and the lower the proinsulin conversion. We found evidence for a genetic basis of adipose tissue lipolysis resulting from common SNPs in CIDEA, AMP-activated protein kinase subunits, and cAMP signaling components. A genetic score of lipolysis-increasing alleles determined lower visceral fat mass and lower proinsulin conversion.

Prediction of Circulating Adipokine Levels Based on Body Fat Compartments and Adipose Tissue Gene Expression

Background: Adipokines are hormones secreted from adipose tissue (AT), and a number of them have been established as risk factors for chronic diseases. However, it is not clear whether and to what extent adiposity, gene expression, and other factors determine their circulating levels. Objectives: To assess to what extent adiposity, as measured by the amount of subcutaneous AT (SAT) and visceral AT (VAT) using magnetic resonance imaging, and gene expression levels in SAT determine plasma concentrations of the adipokines adiponectin, leptin, soluble leptin receptor, resistin, interleukin 6, and fatty acid-binding protein 4 (FABP4). Methods: We performed a cross-sectional analysis of 156 participants from the EPIC Potsdam cohort study and analyzed multiple regression models and partial correlation coefficients. Results: For leptin and FABP4 concentrations, 81 and 45% variance were explained by SAT mass, VAT mass, and gene expression in SAT in multivariable regression models. For the remaining adipokines, AT mass and gene expression explained <16% variance of plasma concentrations. Gene expression in SAT was a less important predictor compared to AT mass. SAT mass was a better predictor than VAT mass for leptin (partial correlation r = 0.81, 95% confidence interval 0.75–0.86, vs. r = 0.58, 95% confidence interval 0.46–0.67), while differences between AT compartments were small for the other adipokines. Conclusions: While plasma levels of leptin and FABP4 can be explained in a large and medium part by the amount of AT and SAT gene expression, surprisingly, these predictors explained only little variance for all other investigated adipokines.