Abdominal Fat Depots Research Articles

Associations of maternal periconceptional alcohol consumption with offspring prehypertension/hypertension at age 6 years: the Growing Up in Singapore Towards healthy Outcomes prospective mother-offspring cohort study.

To evaluate the relationship of the levels of maternal alcohol consumption during the 1 year before pregnancy recognition with childhood cardiorenal, metabolic, and neurocognitive health. In 1106 women and their children from the Growing Up in Singapore Towards healthy Outcomes mother-offspring cohort, quantity of maternal alcohol consumption in the 12 months prior to pregnancy recognition was categorized as high (≥75th percentile: 1.9 g/day), low (<1.9 g/day), and none, and frequency of alcohol consumption was categorized as high (≥2-3 times/week), low (<2-3 times/week), and none. Offspring MRI-based abdominal fat depot, kidney, and brain volumes, blood pressure, metabolic syndrome score, and cognitive intelligence scores were assessed. Child prehypertension/hypertension at age 6 years was defined using a simplified pediatric threshold of 110/70 mmHg. The average maternal alcohol consumption in the year prior to pregnancy recognition was 2.5 g/day, which is lower than the daily maximal limit of one standard drink (10 g) recommended for women by Singapore's Ministry of Health. After adjusting for participant characteristics, alcohol consumption at least 1.9 g/day was associated with over two-fold higher risk (risk ratio = 2.18, P = 0.013) of child prehypertension and 15% greater kidney growth between early infancy and age 6 years (P = 0.040) compared with abstinence. Alcohol consumption was not associated with metabolic and neurocognitive health at age 6-7 years. The associations with high frequency of alcohol consumption were concordant with those obtained for quantity of alcohol consumption. Maternal self-reported alcohol consumption at least 1.9 g/day prior to pregnancy recognition was associated with increased risk of child prehypertension and rapid kidney growth. Our findings highlight the potential detrimental effects of low periconceptional alcohol consumption, below national guidelines on offspring cardiorenal health.

Pancreas Fat, an Early Marker of Metabolic Risk? A Magnetic Resonance Study of Chinese and Caucasian Women: TOFI_Asia Study

ObjectivePrevalence of type 2 diabetes (T2D) is disproportionately higher in younger outwardly lean Asian Chinese compared to matched Caucasians. Susceptibility to T2D is hypothesised due to dysfunctional adipose tissue expansion resulting in adverse abdominal visceral and organ fat accumulation. Impact on early risk, particularly in individuals characterised by the thin-on-the-outside-fat-on-the-inside (TOFI) phenotype, is undetermined.MethodsSixty-eight women [34 Chinese, 34 Caucasian; 18–70 years; body mass index (BMI), 20–45 kg/m2] from the TOFI_Asia study underwent magnetic resonance imaging and spectroscopy to quantify visceral, pancreas, and liver fat. Total body fat was (TBF) assessed by dual-energy x-ray absorptiometry, and fasting blood biomarkers were measured. Ethnic comparisons, conducted using two-sample tests and multivariate regressions adjusted for age, % TBF and ethnicity, identified relationships between abdominal ectopic fat depots with fasting plasma glucose (FPG), insulin resistance (HOMA2-IR), and related metabolic clinical risk markers in all, and within ethnic groups.ResultsDespite being younger and of lower bodyweight, Chinese women in the cohort had similar BMI and % TBF compared to their Caucasian counterparts. Protective high-density lipoprotein cholesterol, total- and high-molecular weight adiponectin were significantly lower, while glucoregulatory glucagon-like peptide-1 and glucagon significantly higher, in Chinese. There were no ethnic differences between % pancreas fat and % liver fat. However, at low BMI, % pancreas and % liver fat were ∼1 and ∼2% higher in Chinese compared to Caucasian women. In all women, % pancreas and visceral adipose tissue had the strongest correlation with FPG, independent of age and % TBF. Percentage (%) pancreas fat and age positively contributed to variance in FPG, whereas % TBF, amylin and C-peptide contributed to IR which was 0.3 units higher in Chinese.ConclusionPancreas fat accumulation may be an early adverse event, in TOFI individuals, with peptides highlighting pancreatic dysfunction as drivers of T2D susceptibility. Follow-up is warranted to explore causality.

Effects of Experimental Sleep Restriction on Energy Intake, Energy Expenditure, and Visceral Obesity

BackgroundAlthough the consequences of sleep deficiency for obesity risk are increasingly apparent, experimental evidence is limited and there are no studies on body fat distribution. ObjectivesThe purpose of this study was to investigate the effects of experimentally-induced sleep curtailment in the setting of free access to food on energy intake, energy expenditure, and regional body composition. MethodsTwelve healthy, nonobese individuals (9 males, age range 19 to 39 years) completed a randomized, controlled, crossover, 21-day inpatient study comprising 4 days of acclimation, 14 days of experimental sleep restriction (4 hour sleep opportunity) or control sleep (9 hour sleep opportunity), and a 3-day recovery segment. Repeated measures of energy intake, energy expenditure, body weight, body composition, fat distribution and circulating biomarkers were acquired. ResultsWith sleep restriction vs control, participants consumed more calories (P = 0.015), increasing protein (P = 0.050) and fat intake (P = 0.046). Energy expenditure was unchanged (all P > 0.16). Participants gained significantly more weight when exposed to experimental sleep restriction than during control sleep (P = 0.008). While changes in total body fat did not differ between conditions (P = 0.710), total abdominal fat increased only during sleep restriction (P = 0.011), with significant increases evident in both subcutaneous and visceral abdominal fat depots (P = 0.047 and P = 0.042, respectively). ConclusionsSleep restriction combined with ad libitum food promotes excess energy intake without varying energy expenditure. Weight gain and particularly central accumulation of fat indicate that sleep loss predisposes to abdominal visceral obesity. (Sleep Restriction and Obesity; NCT01580761)

Aberrant overexpression of HOTAIR inhibits abdominal adipogenesis through remodelling of genome-wide DNA methylation and transcription

ObjectiveAbdominal adiposity is strongly associated with diabetic and cardiovascular comorbidities. The long noncoding RNA HOTAIR (HOX Transcript Antisense Intergenic RNA) is an important epigenetic regulator with fat depot-specific expression. Its functional roles and epigenetic regulation in abdominal adipogenesis remain uncertain. MethodsWe collected different fat depots from healthy, severely obese, and uraemic subjects to measure fat-depot specific gene expression and quantify regional adiposity via dual-energy X-ray absorptiometry (DXA). HOTAIR was overexpressed to evaluate its functional roles. Reduced representation bisulfite sequencing (RRBS), RNA-sequencing, real-time qPCR and RNA/chromatin immunoprecipitation were performed to analyse HOTAIR-mediated epigenetic regulation. ResultsA negative correlation between adipose tissue HOTAIR expression (arm or abdominal subcutaneous fat depots) and regional adiposity under the status of severe obesity or uraemia was observed. HOTAIR overexpression using human immortalized abdominal preadipocytes further revealed its anti-adipogenic effects. Integrative analysis of genome-wide DNA methylation by reduced representation bisulfite sequencing (RRBS) and gene expression was performed. Overall, the differentially methylated genes were functionally enriched for nervous system development, suggesting that HOTAIR may be epigenetically associated with cell lineage commitment. We specifically found that HOTAIR-mediated genes showed strong changes in both DNA methylation and gene expression during abdominal adipogenesis. We observed that two HOTAIR-repressed genes, SLITRK4 and PITPNC1, present an obesity-driven fat-depot specific expression pattern that is positively correlated with the central body fat distribution. ConclusionsOur study indicated that HOTAIR is a key regulator of abdominal adipogenesis via intricate DNA methylation and is likely to be associated with the transcriptional regulation of genes involved in nervous system development and lipid metabolism, such as SLITRK4 and PITPNC1.

Impaired adipocyte glucose transport regulators in morbid obesity - Possible mechanisms contributing to metabolic dysfunction.

Obesity is characterized by hypertrophy and pathological expansion of adipocytes with impaired insulin signaling causing insulin resistance (IR) and metabolic dysfunction. We recently reported decreased expression of glucose transporter-4 (GLUT4) in cultured adipocytes from visceral and abdominal subcutaneous fat depots from patients with morbid obesity and hyperinsulinemia (MOW) and with Type 2 diabetes (MODM). Subsequently, we wanted to study the molecular mechanisms of the glucose transport regulators, p85PI3K, Rab5 and Gapex5 in morbid obesity. Primary in vitro adipocyte cultures were developed from surgical biopsies from visceral (Visc) and abdominal (Sub) and gluteal subcutaneous (Glut) fat depots from 20 lean adults and 36 adults with morbid obesity divided into two groups: 20 with MOW and 16 MODM). mRNA and protein expression (P) of p85PI3K, Rab5 and Gapex5 were studied with RT-PCR and Western Immunoblotting (WI), respectively. In Sub, the P of (1) p85PI3K and Gapex5 were increased in MODM and (2) Rab5 was decreased in MOW and MODM compared to the lean. In Glut, the P of p85PI3K, Rab5 and Gapex5 showed no difference between the lean and MODM. In Sub of MODM (1) reduced RAB5 may possibly contribute to IR and glucose transport dysfunction, (2) increased Gapex5 may be a response to decreased Rab5 in an attempt to increase glucose transport and (3) increased p85PI3K may enhance IR mediating lipid accumulation in MODM. In Glut of MODM, though, the expression of p85PI3K, Rab5 and Gapex5 seems to be similar to that found in lean individuals.

Childhood nutrient intakes are differentially associated with hepatic and abdominal fats in adolescence: The EPOCH study.

The aim of this study was to examine whether nutrient intakes in childhood are associated with abdominal and hepatic fat depots later in adolescence. Using data from 302 participants in the longitudinal Exploring Perinatal Outcomes among CHildren (EPOCH) study, energy partition and nutrient density models were constructed to examine associations of nutrient intakes in childhood (~10 years of age), assessed by food frequency questionnaire, with abdominal subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and hepatic fat in adolescence (~16 years of age). In energy partition models (energy intake not held constant), total, monounsaturated, and polyunsaturated fat intakes in childhood were associated with higher SAT in adolescence (β [95% CI]: 8.5 [0.1-17.1], 25.1 [2.1-48.1], and 59.7 [16.1-103.3] mm2 per 100 kcal/d), higher starch intake was associated with log-hepatic fat (back-transformed β [95% CI]: 1.07 [1.01-1.15] per 100 kcal/d), and, in boys only, higher animal protein intake was associated with VAT (β [95% CI]: 5.3 [0.3-10.3] mm2 per 100 kcal/d). Most associations were unchanged when adjusted for energy intake in nutrient density models. Childhood nutrient intakes were differentially associated with adolescent body fats; specifically, unsaturated fat intake predicted abdominal SAT, animal protein intake predicted VAT, and starch intake predicted hepatic fat. These nutrient intakes may, therefore, be targets for intervention studies aiming to modify adolescent body fat distribution.

Modulation of the dynamics and cellularity of adipose tissues in different fat depots in broilers by dietary dexamethasone.

The objective of this investigation was to determine the effects of dexamethasone (DEX) on the weight and cellularity of abdominal and subcutaneous fat depots. The study was conducted on four broiler chicks (20 chicks per group) fed commercial feed and water ad libitum. The DEX was supplied with feed at 0 mg/kg (non-DEX), 3 mg/kg (DEX-1), 5 mg/kg (DEX-2), and 7 mg/kg (DEX-3) from day 0 to day 28. The entire abdominal and subcutaneous fat depots were collected and weighed after sacrificing five birds from each group on days 14 and 28. The DEX groups had considerably lower (p < 0.05) fat depot weights with dose-related variation noted among the DEX groups. The histological findings revealed the presence of unilocular, round to oval-shaped adipocytes. The DEX-1 and DEX-2 had way lower (p < 0.05) numbers of adipocytes while the DEX-3 had considerably higher (p < 0.05) numbers of adipocytes than the non-DEX. DEX-1 and DEX-2 had larger (p < 0.05) adipocytes whereas DEX-3 had smaller adipocytes than the non-DEX. Adipocyte sizes and fat depot weights were found to have very strong negative relationships. Dietary DEX affects the growth and distribution of abdominal and subcutaneous fat depots and adipocyte cellularity subjected to both dose and duration of DEX treatment.

Associations of fitness and physical activity with specific abdominal fat depots in children with overweight/obesity.

To examine the relationship between physical fitness and physical activity (PA) with specific abdominal fat depots and their potential implications for cardiometabolic risk and insulin resistance (IR) in children with overweight/obesity. A total of 116 children with overweight/obesity (10.7±1.1year, 54% girls) participated in the study. Abdominal visceral (VAT), subcutaneous (ASAT), and intermuscular abdominal adipose tissue (IMAAT) were assessed by magnetic resonance imaging. The cardiometabolic risk (MetS) score and the insulin resistance homeostasis model assessment (HOMA-IR) were calculated. Health-related physical fitness components (treadmill test, and 20m shuttle run, handgrip, standing broad jump and 4×10m tests) were evaluated, and PA was measured (accelerometry). Children were categorized as fit or unfit for each specific fitness test, and as active or inactive. Higher VAT, ASAT, and IMAAT were associated with higher MetS score and HOMA-IR (all p<0.02). A better performance in all fitness tests and total and vigorous PA were strongly associated with lower VAT (all p<0.04), ASAT (all p<0.005), and IMAAT (all p<0.005). Fit or active children had lower VAT, ASAT, and IMAAT (all p<0.03) than their unfit or inactive counterparts. These results reinforce the importance of having adequate fitness and PA levels to reduce abdominal fat accumulation in children. Given that VAT, ASAT, and IMAAT are associated with higher risk of developing cardiovascular diseases and type 2 diabetes, the improvement of physical fitness by the promotion of PA should be goals of lifestyle interventions for improving health in children with overweight/obesity.

Abdominal and gluteofemoral fat depots show opposing associations with postprandial lipemia

High postprandial lipemia is associated with increased risk of cardiovascular disease, independently of fasting lipid concentrations. Abdominal and gluteofemoral fat depots handle lipoproteins differently, which could affect postprandial lipemia and contribute to the relation between abdominal fat distribution and cardiovascular disease risk. We aimed to study the influences of higher abdominal compared with gluteofemoral fat on postprandial lipemia after a high-fat meal in individuals with obesity. A total of 755 adults with obesity from a randomized controlled trial in 7 European countries consumed a liquid high-fat meal. Concentrations of triglycerides (TG), glycerol, free fatty acids, and the cholesterol component of remnant-like particles (RLP), LDL, and HDL were measured postprandially for 3 h. Associations of waist circumference (WC), hip circumference (HC), and waist-hip ratio (WHR) with changes in postprandial lipid concentrations, adjusted for fasting concentrations and BMI, were examined using linear regression models. To assess whether the association of WHR with postprandial lipemia could be causal, we performed instrumental variable analyses using a genetic score of 442 variants known to be associated with WHR adjusted for BMI in 2-stage least-squares regression models. WHR was associated with higher TG and RLP cholesterol concentrations, independent of fasting lipid concentrations and BMI. Instrumental variable analyses suggested that the associations of WHR with postprandial TG (β=0.038 μmol/L*min, SE=0.019 μmol/L*min, P=0.044) and RLP cholesterol concentrations (β=0.059 mmol/L, SE=0.025mmol/L, P=0.020) may be causal. WC and HC showed opposite effects: higher WC was associated with higher TG and RLP cholesterol concentrations whereas higher HC was associated with lower concentrations. Our results suggest that higher fat deposition abdominally versus gluteofemorally may be causally associated with elevated postprandial lipemia after a high-fat meal, independent of fasting lipid concentrations and BMI. Furthermore, higher abdominal and gluteofemoral fat depots show opposing effects on postprandial lipemia.This trial was registered at www.isrctn.com as ISRCTN25867281.

Diabetes and Insulin Resistance Show Association With Femoral Instead of Abdominal Adipocyte Size in Asian Indians

Objectives: Energy intake exceeding expenditure results in adipogenesis, which consists of adipocyte hyperplasia and hypertrophy. Adipocyte hypertrophy is the pathological hallmark of ‘sick fat’ responsible for the development of insulin resistance and diabetes mellitus. In Asian Indians, who show a thin, fat phenotype, the association of adipocyte hypertrophy in various fat depots with insulin resistance and diabetes is not precisely known. The objective of this study is to find an association between adipocyte size of abdominal and thigh fat depot and certain parameters of diabetes mellitus. Material & Methods: In this cross-sectional analytical study, 172 patients were recruited. Abdominal subcutaneous and visceral fat samples were available of 100 patients (Non-diabetics: 56; Diabetics: 44), whereas thigh fat was analyzed in 72 patients (Non-diabetics: 40; Diabetics: 32). All participants had a BMI of less than 30 kg/m2 to negate the effect of obesity on adipocyte size. Fasting glucose, insulin, HbA1c, lipid profile including triglycerides, and total cholesterol were measured in all participants, and HOMA-IR was calculated. Adipocyte size in biopsied tissue after fixation was measured with the help of Motic Panthera Moticam 5 trinocular microscope (BA210LED) and Adobe Photoshop CC image analysis tool. Results: Mean adipocyte size in abdominal visceral compartment in diabetics and non-diabetics were 16610.3 ± 889.5 um2 and 16129.8 ± 878.5 um2 respectively. Whereas, mean adipocyte size in abdominal subcutaneous fat in diabetics and non-diabetics were 15071.0 ± 1261.1 um2 and 14356.8 ± 1004.7 um2 respectively. Adipocyte size difference of both the abdominal compartments between diabetic and non-diabetic group was statistically non-significant (p= 0.70 & 0.65 in omental and abdominal subcutaneous compartments respectively). Mean adipocyte size of thigh in diabetics and non-diabetics were 13070.2 ± 1416.2 um2 and 9020.1 ± 811.1 um2 respectively and difference between adipocyte size between both groups was statistically significant (p = 0.01). Thigh Adipocyte size in diabetic subgroup was positively correlated with HOMA -IR (r = 0.4, p = 0.02), triglycerides (r= 0.4, p = 0.03), waist circumference (r = 0.32, p = 0.03). On multivariate linear regression analysis HOMA-IR (β= 0.45, p=0.00), triglycerides (β=0.38, p=0.01) and waist circumference (β=0.35, p=0.02) are predictor of increased adipocyte size. Conclusion: We found that thigh adipocyte size was significantly larger in diabetics in comparison to non-diabetics, whereas no such difference was found in the abdominal fat compartment. In diabetic patients’ thigh, adipocyte size was positively correlated with HOMA-IR, waist circumference, and triglyceride levels, underlining the role of peripheral fat depots in the pathogenesis of diabetes type 2.

Epicardial, pericardial fat and glucagon-like peptide-1 and -2 receptors expression in stable patients with multivessel coronary artery disease: an association with the renin-angiotensin-aldosterone system.

The expression of glucagon‑like peptide receptors (GLP‑Rs) in epicardial fat (EF) and pericardial fat (PF) depots might be involved in the pathogenesis of cardiovascular diseases. We sought to evaluate the messenger RNA (mRNA) expressions of GLP‑1R and GLP‑2R in EF and PF and their associations with the renin‑angiotensin‑aldosterone system (RAAS) in patients with multivessel coronary artery disease (CAD). Consecutive stable patients with multivessel CAD requiring elective coronary artery bypass grafting were enrolled. Clinical data, anthropometric parameters, and the quantity of fat depots (assessed by cardiovascular magnetic resonance and abdominal ultrasound) were obtained. Fat samples (EF, PF, subcutaneous fat) were taken from patients during cardiac surgery. Relative mRNA expression of GLP‑1R, GLP‑2R, and RAAS components (angiotensin II receptor type 1, angiotensinogen, angiotensin I-converting enzyme 1, and angiotensinI-converting enzyme 2) were assessed in those fat depots. Fifty‑three patients (64.7 [7.4] years) were included in the final analysis. We found that only the relative expression of GLP‑2R was lower in PF compared with subcutaneous fat (reference). Ultrasound abdominal fat depots were associated with both GLP‑1R and GLP‑2R in PF. GLP‑1R and GLP‑2R showed significant correlations with RAAS components in both EF and PF. In stable patients with MVD, the relative mRNA expression for both GLP receptors revealed significant associations with majority of analysed RAAS components.

Ultrasound measures of abdominal fat layers correlate with metabolic syndrome features in patients with obesity.

SummaryObjectiveAbdominal fat ultrasound (US) is a simple clinical tool that may allow measures of fat depots not visible using common dual‐energy X‐ray absorptiometry (DEXA) or computerized tomography (CT) imaging. The aim of this study was to validate the technique, give measures of superficial and profound subcutaneous, preperitoneal, omental and perirenal (retroperitoneal) fat and correlate them with MS markers.MethodsSequential US measures of these five abdominal fat layers were done at 397 adults. Blood pressure (BP), body mass index (BMI), waist, body fat %, HOMA‐IR index (homeostatic model assessment of insulin resistance), lipid profile and leptin were recorded. Metabolic syndrome (MS) was defined according to Cholesterol education programme adult treatment panel III (ATPIII) criteria.Results Subcutaneous and omental fat were increased among people with obesity, whereas preperitoneal and perirenal fat did not show any difference according to BMI or waist. Women showed thicker subcutaneous fat (both superficial and profound), whereas men had bigger omental fat. Both postmenopausal and diabetic patients had changes in omental fat only, whereas patients with fatty liver showed thicker preperitoneal and perirenal fat, as well. MS patients showed both thicker perirenal and omental fat. A cut‐off of 54 mm in male (M)/34 mm in female (F) of omental fat and 22.5 mm (M)/12.5 mm (F) of perirenal fat could be predictive of later MS onset.ConclusionsUS is a valid method to measure all different abdominal fat depots. Omental and perirenal fat measures may classify patients at risk for MS. Preperitoneal fat depot may also correlate with fatty liver disease.

Immunomodulatory and Antioxidative potentials of adipose-derived Mesenchymal stem cells isolated from breast versus abdominal tissue: a comparative study

BackgroundAdipose-derived stem cells (ASCs) are considered ideal candidates for both research and cellular therapy due to ease of access, large yield, feasibility, and efficacy in preclinical and clinical studies. Unlike the subcutaneous abdominal fat depot, breast ASCs features are still not well recognized, limiting their possible therapeutic use. ASCs were found to exert immunomodulatory and antioxidative activities for maintaining homeostasis and functionality of diseased/damaged tissues. This study aims to investigate the immunomodulatory and antioxidative potentials of breast versus abdominal isolated ASCs to find out which anatomical site provides ASCs with better immunoregulatory and oxidative stress resistance capabilities.MethodsASCs were isolated from abdominal and breast tissues. Gene expression analysis was conducted for a panel of immunomodulatory and antioxidative genes, as well as adipokines and proliferation genes. Flow cytometric analysis of a group of immunomodulatory surface proteins was also performed. Finally, the significantly expressed genes have undergone protein-protein interaction and functional enrichment in silico analyses.ResultsOur results revealed similar morphological and phenotypic characteristics for both breast and abdominal ASCs. However, a significant elevation in the expression of two potent immunosuppressive genes, IL-10 and IDO as well as the expression of the multifaceted immunomodulatory adipokine, visfatin, was detected in breast versus abdominal ASCs. Moreover, a significant overexpression of the antioxidative genes, GPX1, SIRT5, and STAT3 and the proliferation marker, Ki67, was also observed in breast ASCs relative to abdominal ones. In silico analysis showed that both of the differentially upregulated immunomodulatory and antioxidative mediators integratively involved in multiple biological processes and pathways indicating their functional association.ConclusionBreast ASCs possess superior immunomodulatory and antioxidative capabilities over abdominal ASCs. Our findings shed light on the possible therapeutic applications of breast ASCs in immune-related and oxidative stress-associated diseases.

Mouse Abdominal Fat Depots Reduced by Butyric Acid-Producing Leuconostoc mesenteroides.

The activation of peroxisome proliferator-activated rece ptor gamma (PPAR-γ) is known to induce the differentiation of adipocytes. This study aimed to investigate the probiotic effect of Leuconostoc mesenteroides (L. mesenteroides) on high-fat diet (HFD)-induced PPAR-γ activation and abdominal fat depots. Incubation of differentiated 3T3-L1 adipocytes with media of L. mesenteroides EH-1, a butyric acid-producing strain, significantly reduced the amounts of lipid droplets. The oral administration of L. mesenteroides EH-1 produced large amounts (>1 mM) of butyric acid in cecum and attenuated the HFD-induced upregulation of PPAR-γ and accumulation of abdominal fats in mice. The combination of 2% glucose with L. mesenteroides EH-1 increased the production of butyric acid and potentiated the probiotic activity of L. mesenteroides EH-1 against the formation of lipid droplets in 3T3-L1 adipocytes as well as abdominal fats in HFD-fed mice. The inhibition of free fatty acid receptor 2 (Ffar2) by its antagonist, GLPG-0974, markedly diminished the probiotic effects of L. mesenteroides EH-1 plus glucose on the suppression of HFD-induced PPAR-γ and abdominal fats. Besides demonstrating the probiotic value of L. mesenteroides EH-1, our results highlight the possible therapy targeting the butyric acid-activated Ffar2 pathway to reduce abdominal fats.

Change in abdominal, but not femoral subcutaneous fat CT-radiodensity is associated with improved metabolic profile after bariatric surgery

Background and aimsComputed tomography (CT)-derived adipose tissue radiodensity represents a potential noninvasive surrogate marker for lipid deposition and obesity-related metabolic disease risk. We studied the effects of bariatric surgery on CT-derived adipose radiodensities in abdominal and femoral areas and their relationships to circulating metabolites in morbidly obese patients. Methods and resultsWe examined 23 morbidly obese women who underwent CT imaging before and 6 months after bariatric surgery. Fifteen healthy non-obese women served as controls. Radiodensities of the abdominal subcutaneous (SAT) and visceral adipose tissue (VAT), and the femoral SAT, adipose tissue masses were measured in all participants. Circulating metabolites were measured by NMR. At baseline, radiodensities of abdominal fat depots were lower in the obese patients as compared to the controls. Surprisingly, radiodensity of femoral SAT was higher in the obese as compared to the controls. In the abdominal SAT depot, radiodensity strongly correlated with SAT mass (r = -0.72, p < 0.001). After surgery, the radiodensities of abdominal fat increased significantly (both p < 0.01), while femoral SAT radiodensity remained unchanged. Circulating ApoB/ApoA-I, leucine, valine, and GlycA decreased, while glycine levels significantly increased as compared to pre-surgical values (all p < 0.05). The increase in abdominal fat radiodensity correlated negatively with the decreased levels of ApoB/ApoA-I ratio, leucine and GlycA (all p < 0.05). The increase in abdominal SAT density was significantly correlated with the decrease in the fat depot mass (r = -0.66, p = 0.002). ConclusionHigher lipid content in abdominal fat depots, and lower content in femoral subcutaneous fat, constitute prominent pathophysiological features in morbid obesity. Further studies are needed to clarify the role of non-abdominal subcutaneous fat in the pathogenesis of obesity. Clinical trial registration numberNCT01373892.

2032-P: Adipose Tissue Inflammation after Weight Loss

Background: Studies of changes in adipose tissue (AT) inflammation after weight loss have conflicting results. Our aim was to evaluate the changes in AT macrophages, senescence and AT insulin resistance after weight loss. Methods: Twenty-five participants (18 women) with obesity underwent a lifestyle intervention weight loss program and abdominal-femoral AT biopsies. AT insulin resistance was estimated calculating the insulin concentration that suppresses lipolysis by 50% (IC50) during a hyperinsulinemic-euglycemic clamp. Immunohistochemistry was used to estimate total adipose tissue macrophage (ATM) content (CD68+), pro-inflammatory ATM (CD14+), anti-inflammatory ATM (CD206+). Senescent cells in AT were identified by senescence associated β-galactosidase staining. All parameters were assessed before and after weight loss. Results: Median BMI was 34 kg/m2 (IQR, 32-35). A median percent weight loss of 10.2% (IQR, 6.5-12.1) resulted in a mean IC50 reduction of -6.2 ± 13 µIU/mL, p=0.03. There was no significant change in ATM content in the abdominal or femoral fat depots after weight loss, except for an increase in CD68 ATMs (mean change 4.5 ± 7.1 ATM/100 adipocytes, P=0.02) in the femoral depot. The proportion of senescent pre-adipocytes in abdominal and femoral depots remained unchanged after weight loss. In the abdominal depot, there was no relationship between IC 50 and CD68 or CD206 ATMs after weight loss, R2= 0.11, P=0.15 and R2= 0.08, P =0.22, for CD68 and CD206 ATMs respectively. There was a weak negative relationship between CD14 ATMs and IC 50 (R2=0.2, P =0.04). In the femoral depot, there was a weak negative relationship between IC 50 and CD68 ATMs (R2=0.23, P=0.04), and no relationship between IC 50 and CD14 ATMs (R2= 0.2, P=0.06) or CD206 ATMs after weight loss (R2= 0.06, P=0.33). Conclusion: Moderate weight loss is not associated with reduction in ATM content or senescent pre-adipocytes, despite an improvement in AT insulin resistance. Our results suggest that recruitment of some populations of ATMs increases after weight loss. Disclosure A.E. Espinosa De Ycaza: None. E. Søndergaard: None. M. Morgan-Bathke: None. D.A. Delivanis: None. B.G. Carranza Leon: None. K. Lytle: None. M.D. Jensen: None.

Vertebral Bone Marrow Fat Is independently Associated to VAT but Not to SAT: KORA FF4-Whole-Body MR Imaging in a Population-Based Cohort.

The objective of the current study was to assess the relationship of bone marrow adipose tissue (BMAT) content to abdominal fat depots, including visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), as well as cardiovascular risk factors (CVRF) beyond physical activity in a population-based cohort study undergoing whole-body magnetic resonance (MR) imaging. Subjects of the Cooperative Health Research in the Augsburg Region (KORA) FF4 study without known cardiovascular disease underwent fat fraction quantification in vertebrae (BMATL1/L2) via a 2-point T1-weighted volumetric interpolated breath-hold examination (VIBE) Dixon sequence. The same MR sequence was applied to quantify VAT and SAT volume. Subjects’ characteristics, including physical activity, were determined through standardized exams and self-assessment questionnaires. Univariate and multivariate linear regression were applied. In the cohort of 378 subjects (56 ± 9.1years; 42.1% female), BMATL1/L2 was 54.3 ± 10.1%, VAT was 4.54 ± 2.71 L, and SAT was 8.10 ± 3.68 L. VAT differed significantly across BMATL1/L2 tertiles (3.60 ± 2.76 vs. 4.92 ± 2.66 vs. 5.11 ± 2.48; p < 0.001), there was no significant differences for SAT (p = 0.39). In the fully adjusted model, VAT remained positively associated with BMATL1/L2 (β = 0.53, p = 0.03). Furthermore, BMATL1/L2 was associated with age (β = 5.40 per 10-years, p < 0.001), hemoglobin A1c (HbA1c; β = 1.55 per 1%, p = 0.04), lipids (β = 0.20 per 10 mg/dL triglycerides; β = 0.40 per 10 mg/dL low-density lipoprotein (LDL); β =−3.21 lipid-lowering medication; all p < 0.05), and less physical activity (β = 3.7 “no or nearly no exercise” as compared to “≥2 h per week, regularly”, p = 0.003); gender was not significantly different (p = 0.57). In the population-based cohort, VAT but not SAT were associated with higher BMATL1/L2 independently of physical activity and other cardiovascular risk factors. Further, BMATL1/L2 increased with older age, less physical activity, higher HbA1c, and increased lipids but decreased with lipid-lowering medication.

PECULIARITIES OF METABOLIC CHANGES IN ASTHMA

The aim: Revealing of clinical-pathogenetic peculiarities in manifestations of uncontrolled As+MS. Materials and methods: Sixty-five cases, divided into 2 groups: Group I - severe As (n=20), Group 2 - severe As+MS (n=45). The general clinical examination included fasting blood glucose, insulin level, HOMA-IR index, body mass index (BMI), spirometry, levels of ММР-9, МСР-1, IL-8 and IL-12. Results: In Group I, 20 patients (100%) had obstructive respiratory dysfunction. Group II had 13 cases (28.88%) with the restrictive, 15 (33.33%) with the obstructive and 17 (37.77%) with the mixed types. BMI revealed: Group I had the normal mass (BMI averaged 24.62 [22.76; 25.71]; Group II had 21 overweighed cases (46.66%) and 24 (53.33%) with grade 1 obesity, averaging 29.70 [28.35; 31.23]. Correlation analysis in Group II showed significant correlations between: age and WHR (r=0.52, p<0.001) (increase of abdominal fat depots during life), FEV1 and BMI (r=-0.63, р<0.001) (obesity affects pulmonary function). IL-8 and IL-12 levels in Group II were increased, respectively, by 27.86 and 13.18 times versus Group I. A relationship was found between MCP-1 and MMP-9 (r=0.77, р<0.05), Group II revealed direct correlation between MCP-1 and total FEV1 (r=0.53, р<0.05). Conclusions: Overweight and obesity in As+MS deteriorate respiratory function versus the same indices in isolated As. Relationships between proinflammatory cytokines and MMP-9 and MCP-1 prove pathogenetic peculiarities of systemic inflammation and metabolic homeostasis. As and MS can cause their coexistence, facilitating development of mutual aggravation.

Decreased adipocyte glucose transporter 4 (GLUT4) and aquaglyceroporin-7 (AQP7) in adults with morbid obesity: possible early markers of metabolic dysfunction.

Morbid obesity (BMI > 40) is often accompanied by metabolic disorders. In adipose tissue, serine/threonine kinase PKBβ/AktΙΙ plays a role in glucose uptake, mediated by glucose transporter 4 (GLUT4). The insulin pathway also affects aquaglyceroporin-7 (AQP7), which mediates lipolysis-derived glycerol efflux into the bloodstream. The aim of our study was to investigate the molecular mechanisms in adipocytes of adults with morbid obesity that may lead to insulin resistance (IR) and diabetes mellitus type 2 (DM2) in morbid obesity. Primary in vitro adipocyte cultures were developed from surgical biopsies from visceral (Visc), abdominal (Sub), and gluteal subcutaneous (Glut) fat depots, from 20 lean adults and 36 adults with morbid obesity (OB), divided into two groups: 20 without (MOW) and 16 with DM2 (MODM). mRNA and protein expression (PE) of AktΙΙ, AQP7, and GLUT4 were studied with RT-PCR and Western immunoblotting (WI), respectively. The PE of (1) AktII and basal phosphorylated AktII (pAktII) showed no difference within the groups, (2) the 37kDa and 34kDa isoforms of AQP7 were decreased in Visc/Sub from OB/MOW/MODM, (3) GLUT4 was decreased in Visc/Sub from OB/MOW/MODM, and (4) the 34kDa isoform of AQP7 was decreased in Sub of MODM compared with MOW. Decreased 37kDa (presented in this study as a novel isoform) and 34kDa isoforms of AQP7 in MOW and MODM may cause reduced lipolysis, enhancement of adipocyte hypertrophy, and impairment of insulin, signaling possibly reflected by low GLUT4 expression. This may potentially cause systemic IR, since decreased adipose GLUT4 expression may affect whole-body insulin sensitivity, increasing the risk for DM2. Furthermore, decreased subcutaneous AQP7 34kDa could represent an early marker of IR.

Gain and loss of subcutaneous and abdominal fat depot mass from late pregnancy to 100 days in milk in German Holsteins.

This research paper addresses the hypothesis that in times of negative energy balance around parturition in dairy cattle, lipids stored in adipocytes are mobilised in a more intensive manner out of the abdominal depots than out of the subcutaneous adipose tissues. Furthermore, the impact of niacin supplementation and energy density of the ration on adipose tissue mass gain and loss was assessed. Absolute masses of subcutaneous (SCAT), retroperitoneal (RPAT), omental (OMAT), mesenterial (MAT) and abdominal adipose tissue as a whole (AAT) were estimated by ultrasonography at -42, 3, 21 and 100 DIM. Absolute and relative daily gain during dry period (-42 to 3 DIM) and loss in fresh cow period (3 to 21 DIM) and early lactation period (22 to 100 DIM) were calculated. Feeding regime neither by niacin nor by energy density exerted any effect on adipose tissue masses. The AAT was always bigger than SCAT, but RPAT, OMAT and MAT did not differ amongst each other. All depot masses showed similar patterns with an increase during dry period and a decrease after calving. In fresh cow period AAT absolutely and relatively lost more mass than SCAT. This confirms that AAT is more intensively mobilised than SCAT during that time span. Further absolute daily gain during dry period was strongly negatively correlated with absolute daily loss during fresh cow period. This underlines the impact of individual body condition on adipose mobilisation in periparturient dairy cows. According to these results, it has to be taken into account that the largest amount of fat mobilised in the fresh cow period origins from AAT. This might impact the pattern of adipose derived metabolites and metabolic effectors interacting in physiological and deregulated adaptation to negative energy balance.