The Relationship of Omental and Subcutaneous Adipocyte Size to Metabolic Disease in Severe Obesity

Objective

Several studies have reported the existence of a subgroup of obese individuals with normal metabolic profiles. It remains unclear what factors are responsible for this phenomenon. We proposed that adipocyte size might be a key factor in the protection of metabolically healthy obese (MHO) individuals from the adverse effects of obesity.

Subjects

Thirty-five patients undergoing bariatric surgery were classified as MHO (n = 15) or metabolically unhealthy obese (MUO, n = 20) according to cut-off points adapted from the International Diabetes Federation definition of the metabolic syndrome. Median body mass index (BMI) was 48 (range 40–71).

Results

There was a moderate correlation between omental adipocyte size and subcutaneous adipocyte size (r = 0.59, p<0.05). The MHO group had significantly lower mean omental adipocyte size (80.9±10.9 µm) when compared with metabolically unhealthy patients (100.0±7.6 µm, p<0.0001). Mean subcutaneous adipocyte size was similar between the two groups (104.1±8.5 µm versus 107.9±7.1 µm). Omental, but not subcutaneous adipocyte size, correlated with the degree of insulin resistance as measured by HOMA-IR (r = 0.73, p<0.0005), as well as other metabolic parameters including triglyceride/HDL-cholesterol ratio and HbA1c. Twenty-eight patients consented to liver biopsy. Of these, 46% had steatohepatitis and fibrosis. Fifty percent (including all the MHO patients) had steatosis only. Both omental and subcutaneous adipocyte size were significantly associated with the degree of steatosis (r = 0.66, p<0.0001 and r = 0.63, p<0.005 respectively). However, only omental adipocyte size was an independent predictor of the presence or absence of fibrosis.

Conclusion

Metabolically healthy individuals are a distinct subgroup of the severely obese. Both subcutaneous and omental adipocyte size correlated positively with the degree of fatty liver, but only omental adipocyte size was related to metabolic health, and possibly progression from hepatic steatosis to fibrosis.     

Adipocyte Hypertrophy,Inflammation and Fibrosis Characterize Subcutaneous Adipose Tissue of Healthy,Non-Obese Subjects Predisposed to Type 2 Diabetes

Background

The adipose tissue is important for development of insulin resistance and type 2 diabetes and adipose tissue dysfunction has been proposed as an underlying cause. In the present study we investigated presence of adipocyte hypertrophy, and gene expression pattern of adipose tissue dysfunction in the subcutaneous adipose tissue of healthy, non-obese subjects predisposed to type 2 diabetes compared to matched control subjects with no known genetic predisposition for type 2 diabetes.

Method

Seventeen healthy and non-obese subjects with known genetic predisposition for type 2 diabetes (first-degree relatives, FDRs) and 17 control subjects were recruited. The groups were matched for gender and BMI and had similar age. Glucose tolerance was determined by an oral glucose tolerance test and insulin sensitivity was calculated using HOMA-index. Blood samples were collected and subcutaneous abdominal adipose tissue biopsies obtained for gene expression analysis and adipocyte cell size measurement.

Results

Our findings show that, in spite of similar age, BMI and percent body fat, FDRs displayed adipocyte hypertrophy, as well as higher waist/hip ratio, fasting insulin levels, HOMA-IR and serum triglycerides. Adipocyte hypertrophy in the FDR group, but not among controls, was associated with measures of impaired insulin sensitivity. The adipocyte hypertrophy was accompanied by increased inflammation and Wnt-signal activation. In addition, signs of tissue remodeling and fibrosis were observed indicating presence of early alterations associated with adipose tissue dysfunction in the FDRs.

Conclusion

Genetic predisposition for type 2 diabetes is associated with impaired insulin sensitivity, adipocyte hypertrophy and other markers of adipose tissue dysfunction. A dysregulated subcutaneous adipose tissue may be a major susceptibility factor for later development of type 2 diabetes.     

Serum Glycine Is Associated with Regional Body Fat and Insulin Resistance in Functionally-Limited Older Adults

Background

Metabolic profiling may provide insight into biologic mechanisms related to age-related increases in regional adiposity and insulin resistance.

Objectives

The objectives of the current study were to characterize the association between mid-thigh intermuscular and subcutaneous adipose tissue (IMAT, SCAT, respectively) and, abdominal adiposity with the serum metabolite profile, to identify significant metabolites as further associated with the homeostasis model assessment of insulin resistance (HOMA-IR), and, to develop a HOMA-IR associated metabolite predictor set representative of regional adiposity, in 73 functionally-limited (short physical performance battery ≤10; SPPB) older adults (age range, 70–85 y).

Methods

Fasting levels of 181 total metabolites, including amino acids, fatty acids and acylcarnitines were measured with use of an untargeted mass spectrometry-based metabolomic approach. Multivariable-adjusted linear regression was used in all analyses.

Results

Thirty-two, seven and one metabolite(s) were found to be associated with IMAT, abdominal adiposity and, SCAT, respectively, including the amino acid glycine, which was positively associated with SCAT and, negatively associated with both IMAT and abdominal adiposity. Glycine and four metabolites found to be significantly associated with regional adiposity were additionally associated with HOMA-IR. Separate stepwise regression models identified glycine as a HOMA-IR associated marker of both IMAT (model R² = 0.51, p<0.0001) and abdominal adiposity (model R² = 0.41, p<0.0001).

Conclusion

Our findings for a positive association between glycine with SCAT but, a negative association between glycine with IMAT and abdominal adiposity supports the hypothesis that SCAT metabolic processes are different from that found in other fat depots. In addition, because of the significant associations found between glycine with HOMA-IR, IMAT, SCAT and abdominal adiposity, our results suggest glycine as a serum biomarker of both insulin sensitivity and regional fat mass in functionally-limited older adults.     

Validation of Dual Energy X-Ray Absorptiometry Measures of Abdominal Fat by Comparison with Magnetic Resonance Imaging in an Indian Population

Objective

Abdominal adiposity is an important risk factor for diabetes and cardiovascular disease in Indians. Dual energy X-ray absorptiometry (DXA) can be used to determine abdominal fat depots, being more accessible and less costly than gold standard measures such as magnetic resonance imaging (MRI). DXA has not been fully validated for use in South Asians. Here, we determined the accuracy of DXA for measurement of abdominal fat in an Indian population by comparison with MRI.

Design

146 males and females (age range 18–74, BMI range 15–46 kg/m²) from Hyderabad, India underwent whole body DXA scans on a Hologic Discovery A scanner, from which fat mass in two abdominal regions was calculated, from the L1 to L4 vertebrae (L1L4) and from the L2 to L4 vertebrae (L2L4). Abdominal MRI scans (axial T1-weighted spin echo images) were taken, from which adipose tissue volumes were calculated for the same regions.

Results

Intra-class correlation coefficients between DXA and MRI measures of abdominal fat were high (0.98 for both regions). Although at the level of the individual, differences between DXA and MRI could be large (95% of DXA measures were between 0.8 and 1.4 times MRI measures), at the sample level, DXA only slightly overestimated MRI measures of abdominal fat mass (mean difference in L1L4 region: 2% (95% CI:0%, 5%), mean difference in L2L4 region:4% (95% CI: 1%, 7%)). There was evidence of a proportional bias in the association between DXA and MRI (correlation between difference and mean −0.3), with overestimation by DXA greater in individuals with less abdominal fat (mean bias in leaner half of sample was 6% for L1L4 (95%CI: 2, 11%) and 7% for L2L4 (95% CI:3,12%).

Conclusions

DXA measures of abdominal fat are suitable for use in Indian populations and provide a good indication of abdominal adiposity at the population level.     

Reduction in Adiposity, β-Cell Function,Insulin Sensitivity,and Cardiovascular Risk Factors: A Prospective Study among Japanese with Obesity

Background

A reduction in adiposity may be associated with an improvement in insulin sensitivity and β-cell function as well as cardiovascular disease (CVD) risk factors; however, few studies have investigated these associations in a longitudinal setting.

Methods

To investigate these associations over a 1-year period, we conducted an observational analysis of 196 Japanese subjects with obesity in the Saku Control Obesity Program. We investigated the relations between changes in adiposity (body mass index [BMI], waist circumference, subcutaneous fat area [SFAT], and visceral fat area [VFAT]) and changes in HbA1c, fasting plasma glucose (FPG), insulin sensitivity index (ISI), the homeostasis model assessment β cell function (HOMA-β), lipids, and blood pressure.

Results

All adiposity changes were positively associated with HbA1c and FPG changes. Reductions in BMI and VFAT were associated with HOMA-β reduction. Reductions in all adiposity measures were associated with an improvement in the ISI. Changes in most adiposity measures were positively associated with changes in blood pressure and lipid levels, except for LDL.

Conclusion

The present findings provide additional supportive evidence indicating that a reduction in adiposity may lead to an improvement in insulin sensitivity and the reduction of CVD risk factors in obese individuals.     

Expression and activity of steroid aldoketoreductases 1C in omental adipose tissue are positive correlates of adiposity in women

We examined expression and activity of steroid aldoketoreductase (AKR) 1C enzymes in adipose tissue in women. AKR1C1 (20alpha-hydroxysteroid dehydrogenase; 20alpha-HSD), AKR1C2 (3alpha-HSD-3), and AKR1C3 (17beta-HSD-5) are involved mainly in conversion of progesterone to 20alpha-hydroxyprogesterone and inactivation of dihydrotestosterone to 5alpha-androstane-3alpha,17beta-diol. Abdominal subcutaneous and omental adipose tissue biopsies were obtained during abdominal hysterectomies in seven women with low visceral adipose tissue (VAT) area and seven age- and total body fat mass-matched women with visceral obesity. Women with elevated VAT areas were characterized by significantly higher omental adipose tissue 20alpha-HSD and 3alpha-HSD-3 mRNA abundance compared with women with low VAT accumulations (1.4- and 1.6-fold differences, respectively; P < 0.05). Omental and subcutaneous adipose tissue 3alpha-HSD activities were significantly higher in women with high vs. low VAT areas (P < 0.05 for both comparisons). Total and visceral adiposities were positively associated with omental 20alpha-HSD mRNA level (r = 0.75, P < 0.003 for fat mass; r = 0.57, P < 0.04 for VAT area) and omental 3alpha-HSD-3 mRNA level (r = 0.68, P < 0.01 for fat mass; r = 0.74, P < 0.003 for VAT area). Enzyme activities in both depots were also positively correlated with adiposity measures. Omental adipose tissue enzyme expression and activity were positively associated with omental adipocyte size and LPL activity. In conclusion, mRNA abundance and activity of AKR1C enzymes in abdominal adipose tissue compartments are positive correlates of adiposity in women. Increased progesterone and/or dihydrotestosterone reduction in abdominal adipose tissue may impact locally on fat cell metabolism.     

Adipocyte hypertrophy, fatty liver and metabolic risk factors in South Asians: the Molecular Study of Health and Risk in Ethnic Groups (mol-SHARE)

Objective

We sought to determine if differences in the distribution and characteristics of adipose tissue between South Asians and white Caucasians account for differences in risk factors for cardiovascular disease.

Research Design and Methods

We recruited 108 healthy South Asians (36.8 years) and white Caucasians (34.2 years) within three BMI strata. Body composition, adipocyte size, abdominal fat area, and hepatic adiposity were assessed and related to fasting glucose, insulin, lipids and adiponectin.

Results

After adjustment for age, sex, and BMI, South Asians compared to white Caucasians had higher ln fasting insulin (mean difference (md): 0.44; 95% CI: 0.20–0.69), lower HDL cholesterol (md: −0.13; 95% CI:−0.26 to −0.01), and lower adiponectin (md: −2.38; 95% CI: −3.59 to −1.17). South Asians also had more body fat (md: 2.69; 95% CI: 0.70 to 4.69), lower lean muscle mass (md: −3.25; 95%CI: −5.35 to −1.14), increased waist to hip ratio (md: 0.03; 95% CI: 0.01–0.05), less superficial subcutaneous abdominal adipose tissue (md: −2.94; 95% CI: −5.56 to−0.32), more deep/visceral to superficial adipose tissue ratio (md 0.34; 95% CI: 0.02 to 0.65), and more liver fat (md: 7.43%; 95% CI: 2.30 to 12.55%). Adipocyte area was increased in South Asians compared to white Caucasians (md: 64.26; 95% CI: 24.3 to 104.1) units². Adjustment for adipocyte area attenuated the ethnic differences in insulin (md: 0.22; 95% CI: −0.07 to 0.51), HDL (md: −0.01; 95% CI: −0.16 to 0.13) and adiponectin (md: −1.11; 95% CI: −2.61 to 0.39). Adjustment for differences in adipocyte area and fat distribution attenuated the ethnic difference in liver fat (md: 5.19; 95% CI: 0.31 to 10.06).

Conclusion

South Asians have an increased adipocyte area compared to white Caucasians. This difference accounts for the ethnic differences in insulin, HDL cholesterol, adiponectin, and ectopic fat deposition in the liver.     

Neighborhood Safety and Adipose Tissue Distribution in African Americans: The Jackson Heart Study

Objective

Patterns of fat distribution are heavily influenced by psychological stress, sex, and among women, by menopause status. Emerging evidence suggests the lack of perceived neighborhood safety due to crime may contribute to psychological stress and obesity among exposed residents. Our objective is to determine if perceived neighborhood safety is associated with abdominal adiposity among African-American men and women, and among pre- and postmenopausal women in the Jackson Heart Study.

Design and Methods

We examined associations between perceived neighborhood safety, fat distribution, and other individual-level covariates among Jackson Heart Study participants (N = 2,881). Abdominal adiposity was measured via computed tomography scans measuring the volumes of visceral, subcutaneous and total adipose tissue. We also measured body mass index (BMI), and waist circumference. Multivariable regression models estimated associations between perceived neighborhood safety, adiposity, and covariates by sex and menopause status.

Results

Adjusting for all covariates, women who strongly disagreed their neighborhood was safe from crime had a higher BMI compared to women who felt safe [Std B 0.083 95% CI (0.010, 0.156)]. Premenopausal women who felt most unsafe had higher BMI, waist circumference, and volumes of visceral and total adipose tissue than those who felt safe [Std B 0.160 (0.021, 0.299), Std B 0.142 (0.003, 0.280), Std B 0.150 (0.014, 0.285), Std B 0.154 (0.019, 0.290), respectively]. We did not identify associations between neighborhood safety and adiposity among men and postmenopausal women.

Conclusions

Our data suggest that abdominal adipose tissue distribution patterns are associated with perceived neighborhood safety in some groups, and that patterns may differ by sex and menopause status, with most associations observed among pre-menopausal women. Further research is needed to elucidate whether there are causal mechanisms underlying sex and menopause-status differences that may mediate associations between perceived safety and abdominal adiposity and potential protective factors that may modify this risk.     

Different anthropometric adiposity measures and their association with cardiovascular disease risk factors: a meta-analysis

Objectives

To investigate which anthropometric adiposity measure has the strongest association with cardiovascular disease (CVD) risk factors in Caucasian men and women without a history of CVD.

Design

Systematic review and meta-analysis.

Methods

We searched databases for studies reporting correlations between anthropometric adiposity measures and CVD risk factors in Caucasian subjects without a history of CVD. Body mass index (BMI), waist circumference, waist-to-hip ratio, waist-to-height ratio and body fat percentage were considered the anthropometric adiposity measures. Primary CVD risk factors were: systolic blood pressure, diastolic blood pressure, high density lipoprotein (HDL) cholesterol, triglycerides and fasting glucose. Two independent reviewers performed abstract, full text and data selection.

Results

Twenty articles were included describing 21,618 males and 24,139 females. Waist circumference had the strongest correlation with all CVD risk factors for both men and women, except for HDL and LDL in men. When comparing BMI with waist circumference, the latter showed significantly better correlations to CVD risk factors, except for diastolic blood pressure in women and HDL and total cholesterol in men.

Conclusions

We recommend the use of waist circumference in clinical and research studies above other anthropometric adiposity measures, especially compared with BMI, when evaluating CVD risk factors.     

Association of Abdominal Obesity with Lumbar Disc Degeneration – A Magnetic Resonance Imaging Study

Purpose

To evaluate whether midsagittal (abdominal) obesity in magnetic resonance imaging (MRI), waist circumference (WC) and body fat percentage are associated with lumbar disc degeneration in early adulthood.

Methods

We obtained the lumbar MRI (1.5-T scanner) of 325 females and 233 males at a mean age of 21 years. Lumbar disc degeneration was evaluated using Pfirrmann classification. We analysed the associations of MRI measures of obesity (abdominal diameter (AD), sagittal diameter (SAD), ventral subcutaneous thickness (VST), and dorsal subcutaneous thickness (DST)), WC and body fat percentage with disc degeneration sum scores using ordinal logistic regression.

Results

A total of 155 (48%) females and 147 (63%) males had disc degeneration. AD and SAD were associated with a disc degeneration sum score of ≥3 compared to disc degeneration sum score of 0–2 (OR 1.67; 95% confidence interval (CI) 1.20–2.33 and OR 1.40; 95% CI 1.12–1.75, respectively) among males, but we found no association among females. WC was also associated with disc degeneration among males (OR 1.03 per one cm; 95% CI 1.00–1.05), but not among females.

Conclusion

Measures of abdominal obesity in MRI and waist circumference were associated with disc degeneration among 21-year-old males.     

Uncovering suitable reference proteins for expression studies in human adipose tissue with relevance to obesity

Background

Protein expression studies based on the two major intra-abdominal human fat depots, the subcutaneous and the omental fat, can shed light into the mechanisms involved in obesity and its co-morbidities. Here we address, for the first time, the identification and validation of reference proteins for data standardization, which are essential for accurate comparison of protein levels in expression studies based on fat from obese and non-obese individuals.

Methodology and Findings

To uncover adipose tissue proteins equally expressed either in omental and subcutaneous fat depots (study 1) or in omental fat from non-obese and obese individuals (study 2), we have reanalyzed our previously published data based on two-dimensional fluorescence difference gel electrophoresis. Twenty-four proteins (12 in study 1 and 12 in study 2) with similar expression levels in all conditions tested were selected and identified by mass spectrometry. Immunoblotting analysis was used to confirm in adipose tissue the expression pattern of the potential reference proteins and three proteins were validated: PARK7, ENOA and FAA. Western Blot analysis was also used to test customary loading control proteins. ENOA, PARK7 and the customary loading control protein Beta-actin showed steady expression profiles in fat from non-obese and obese individuals, whilst FAA maintained steady expression levels across paired omental and subcutaneous fat samples.

Conclusions

ENOA, PARK7 and Beta-actin are proper reference standards in obesity studies based on omental fat, whilst FAA is the best loading control for the comparative analysis of omental and subcutaneous adipose tissues either in obese and non-obese subjects. Neither customary loading control proteins GAPDH and TBB5 nor CALX are adequate standards in differential expression studies on adipose tissue. The use of the proposed reference proteins will facilitate the adequate analysis of proteins differentially expressed in the context of obesity, an aim difficult to achieve before this study.     

Association of Simple Anthropometric Indices and Body Fat with Early Atherosclerosis and Lipid Profiles in Chinese Adults

Objective

The discriminatory capability of different adiposity indices for atherosclerosis and lipid abnormalities remains uncertain. This study aimed to identify the best adiposity index for predicting early atherosclerosis and abnormal lipid profiles among anthropometric parameters and body fat measures in middle-aged and elderly Chinese.

Method

A total of 2,063 women and 814 men (57.6±5.2 y) were recruited for this community-based cross-sectional study. Body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) were assessed. Body fat mass and its percentage values for the whole body and trunk were measured by bioelectrical impedance analysis (BIA). The intima-media thicknesses (IMTs) of the common carotid arteries (CCA), internal carotid arteries (ICA) and bifurcation (BIF) were determined via B-mode ultrasound. The fasting lipid profiles were assessed.

Results

With per SD increase of adiposity indices, the magnitude of the changes of IMT values and lipid profiles was more substantial for WC, WHR and WHtR in both genders. A multivariate logistic regression analysis indicated that WC, WHR and WHtR were more sensitive in predicting the presence of intima-media thickening at the three segments as well as the lipids disturbances in women and men. In general, BIA-derived measures have no added predictive value for IMT-thickening as opposed to those three traditional abdominal measures.

Conclusion

Our findings suggest that abdominal anthropometric measures including WC, WHR and WHtR are sensitive for discriminating carotid atherosclerosis and lipids abnormalities. WC is the best index because of its simplicity in routine use.     

The Association of Serum Total Peptide YY (PYY) with Obesity and Body Fat Measures in the CODING Study

Background

PYY is an appetite suppressing hormone. Low circulating PYY has been linked to greater BMI. However data is controversial and this association has not been verified in large human populations.

Objective

The purpose of this study was to investigate if fasting serum total PYY is associated with obesity status and/or adiposity at the population level.

Design

A total of 2094 subjects (Male-523, Female-1571) participated in this investigation. Total PYY was measured in fasting serum by enzyme-linked immunosorbent assay. Obesity status (NW-normal-weight, OW-overweight and OB-obese) was determined by the Bray Criteria according to body fat percentage measured by dual-energy x-ray absorptiometry and the WHO criteria according to BMI. One-way ANOVA and multiple regression was used to assess the adiposity-specific association between PYY and the following; weight, BMI, waist-circumference, hip-circumference, waist-hip ratio, percent body fat (%BF), trunk fat (%TF), android fat (%AF) and gynoid fat (%GF).

Results

PYY was not significantly different among NW, OW and OB groups defined by neither %BF nor BMI for both men and women. However among women, fasting PYY was positively associated with adiposity measures. Women with the highest (Top 33%) waist-circumference, %BF and %TF had significantly higher PYY (10.5%, 8.3% and 9.2% respectively) than women with the lowest (Bottom 33%). Age, smoking, medication use and menopause were all positively associated with PYY levels in women but not in men.

Conclusion

To our knowledge this is the largest population based study, with the most comprehensive analysis and measures of confounding factors, to explore the relationship of circulating PYY with obesity. Contrary to initial findings in the literature we discovered that PYY was positively associated with body fat measures (waist-circumference, %BF and %TF) in women. Although the effect size of the positive association of PYY with obesity in women is small, and potentially negligible, it may in fact represent a protective response against significant weight gain.     

Hexosamine Biosynthesis Is a Possible Mechanism Underlying Hypoxia’s Effects on Lipid Metabolism in Human Adipocytes

Introduction

Hypoxia regulates adipocyte metabolism. Hexosamine biosynthesis is implicated in murine 3T3L1 adipocyte differentiation and is a possible underlying mechanism for hypoxia’s effects on adipocyte metabolism.

Methods

Lipid metabolism was studied in human visceral and subcutaneous adipocytes in in vitro hypoxic culture with adipophilic staining, glycerol release, and palmitate oxidation assays. Gene expression and hexosamine biosynthesis activation was studied with QRTPCR, immunofluorescence microscopy, and Western blotting.

Results

Hypoxia inhibits lipogenesis and induces basal lipolysis in visceral and subcutaneous human adipocytes. Hypoxia induces fatty acid oxidation in visceral adipocytes but had no effect on fatty acid oxidation in subcutaneous adipocytes. Hypoxia inhibits hexosamine biosynthesis in adipocytes. Inhibition of hexosamine biosynthesis with azaserine attenuates lipogenesis and induces lipolysis in adipocytes in normoxic conditions, while promotion of hexosamine biosynthesis with glucosamine in hypoxic conditions slightly increases lipogenesis.

Conclusions

Hypoxia’s net effect on human adipocyte lipid metabolism would be expected to impair adipocyte buffering capacity and contribute to systemic lipotoxicity. Our data suggest that hypoxia may mediate its effects on lipogenesis and lipolysis through inhibition of hexosamine biosynthesis. Hexosamine biosynthesis represents a target for manipulation of adipocyte metabolism.     

Effect of walking exercise on abdominal fat,insulin resistance and serum cytokines in obese women

[Purpose]

The purpose of the study was to investigate the effect of 12-week walking exercise on abdominal fat, insulin resistance and serum cytokines in obese women.

[Methods]

Following baseline measurements, obese women (N = 20) who met obesity criterion of BMI at 25 kg/m² or greater were randomly assigned to the control (n = 10) or exercise groups (n = 10). Women assigned to the exercise group participated in a walking exercise (with an intensity of 50-60% of predetermined VO²max, a frequency of 3 days per week and duration of 50-70 minutes targeting 400 kcal of energy expenditure per session) for 12 weeks, while women assigned to the control group maintained their sedentary lifestyle. After the 12-week walking intervention, post-test measurements were conducted using the same procedure as the baseline measurement. Analyses of variance with repeated measures were used to evaluate any significant time by group interactions for the measured variables.

[Results]

With respect to body fat parameters, significant time-by-group interactions were found in the abdominal subcutaneous (p = < 0.001) and visceral adipose tissues (p = 0.011). The exercise group had significant reductions in both subcutaneous and visceral adiposity, and the control group had no significant changes in those parameters. Similarly, there were significant time by group interactions in fasting glucose (p = 0.008), HOMA-IR (p = 0.029), serum TNF-α (p = 0.027), and IL-6 (p = 0.048) such that the exercise group had significant reductions in those parameters, with no such significant changes found in the control group. The exercise group also had a significant increase in serum adiponectin (p = 0.002), whereas the control group had no significant change in the parameter.

[Conclusion]

In summary, the current findings suggest that walking exercise can provide a safe and effective lifestyle strategy against abdominal obesity and serum insulin resistance markers in obese women.     

Physiological Response of Adipocytes to Weight Loss and Maintenance

Background

Metabolic processes in adipose tissue are dysregulated in obese subjects and, in response to weight loss, either normalize or change in favor of weight regain.

Objective

To determine changes in adipocyte glucose and fatty acid metabolism in relation to changes in adipocyte size during weight loss and maintenance.

Methods

Twenty-eight healthy subjects (12 males), age 20–50 y, and BMI 28–35 kg/m², followed a very low energy diet for 2 months, followed by a 10-month period of weight maintenance. Body weight, body composition (deuterium dilution and BodPod), protein levels (Western blot) and adipocyte size were assessed prior to and after weight loss and after the 10-month follow-up.

Results

A 10% weight loss resulted in a 16% decrease in adipocyte size. A marker for glycolysis decreased (AldoC) during weight loss in association with adipocyte shrinking, and remained decreased during follow-up in association with weight maintenance. A marker for fatty acid transport increased (FABP4) during weight loss and remained increased during follow-up. Markers for mitochondrial beta-oxidation (HADHsc) and lipolysis (ATGL) were only increased after the 10-month follow-up. During weight loss HADHsc and ATGL were coordinately regulated, which became weaker during follow-up due to adipocyte size-related changes in HADHsc expression. AldoC was the major denominator of adipocyte size and body weight, whereas changes in ATGL during weight loss contributed to body weight during follow-up. Upregulation of ATGL and HADHsc occured in the absence of a negative energy balance and was triggered by adipocyte shrinkage or indicated preadipocyte differentiation.

Conclusion

Markers for adipocyte glucose and fatty acid metabolism are changed in response to weight loss in line with normalization from a dysregulated obese status to an improved metabolic status.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01015508","term_id":"NCT01015508"}}NCT01015508     

MiRNA Expression Profile of Human Subcutaneous Adipose and during Adipocyte Differentiation

Background

Potential regulators of adipogenesis include microRNAs (miRNAs), small non-coding RNAs that have been recently shown related to adiposity and differentially expressed in fat depots. However, to date no study is available, to our knowledge, regarding miRNAs expression profile during human adipogenesis. Thereby, the aim of this study was to investigate whether miRNA pattern in human fat cells and subcutaneous adipose tissue is associated to obesity and co-morbidities and whether miRNA expression profile in adipocytes is linked to adipogenesis.

Methodology/Principal Findings

We performed a global miRNA expression microarray of 723 human and 76 viral mature miRNAs in human adipocytes during differentiation and in subcutaneous fat samples from non-obese (n = 6) and obese with (n = 9) and without (n = 13) Type-2 Diabetes Mellitus (DM-2) women. Changes in adipogenesis-related miRNAs were then validated by RT-PCR. Fifty of 799 miRNAs (6.2%) significantly differed between fat cells from lean and obese subjects. Seventy miRNAs (8.8%) were highly and significantly up or down-regulated in mature adipocytes as compared to pre-adipocytes. Otherwise, 17 of these 799 miRNAs (2.1%) were correlated with anthropometrical (BMI) and/or metabolic (fasting glucose and/or triglycerides) parameters. We identified 11 miRNAs (1.4%) significantly deregulated in subcutaneous fat from obese subjects with and without DM-2. Interestingly, most of these changes were associated with miRNAs also significantly deregulated during adipocyte differentiation.

Conclusions/Significance

The remarkable inverse miRNA profile revealed for human pre-adipocytes and mature adipocytes hints at a closely crosstalk between miRNAs and adipogenesis. Such candidates may represent biomarkers and therapeutic targets for obesity and obesity-related complications.     

Amyloid precursor protein and proinflammatory changes are regulated in brain and adipose tissue in a murine model of high fat diet-induced obesity

Background

Middle age obesity is recognized as a risk factor for Alzheimer''s disease (AD) although a mechanistic linkage remains unclear. Based upon the fact that obese adipose tissue and AD brains are both areas of proinflammatory change, a possible common event is chronic inflammation. Since an autosomal dominant form of AD is associated with mutations in the gene coding for the ubiquitously expressed transmembrane protein, amyloid precursor protein (APP) and recent evidence demonstrates increased APP levels in adipose tissue during obesity it is feasible that APP serves some function in both disease conditions.

Methodology/Principal Findings

To determine whether diet-induced obesity produced proinflammatory changes and altered APP expression in brain versus adipose tissue, 6 week old C57BL6/J mice were maintained on a control or high fat diet for 22 weeks. Protein levels and cell-specific APP expression along with markers of inflammation and immune cell activation were compared between hippocampus, abdominal subcutaneous fat and visceral pericardial fat. APP stimulation-dependent changes in macrophage and adipocyte culture phenotype were examined for comparison to the in vivo changes.

Conclusions/Significance

Adipose tissue and brain from high fat diet fed animals demonstrated increased TNF-α and microglial and macrophage activation. Both brains and adipose tissue also had elevated APP levels localizing to neurons and macrophage/adipocytes, respectively. APP agonist antibody stimulation of macrophage cultures increased specific cytokine secretion with no obvious effects on adipocyte culture phenotype. These data support the hypothesis that high fat diet-dependent obesity results in concomitant pro-inflammatory changes in brain and adipose tissue that is characterized, in part, by increased levels of APP that may be contributing specifically to inflammatory changes that occur.     

Impact of resistant starch on body fat patterning and central appetite regulation

Background

Adipose tissue patterning has a major influence on the risk of developing chronic disease. Environmental influences on both body fat patterning and appetite regulation are not fully understood. This study was performed to investigate the impact of resistant starch (RS) on adipose tissue deposition and central regulation of appetite in mice.

Methodology and Principle Findings

Forty mice were randomised to a diet supplemented with either the high resistant starch (HRS), or the readily digestible starch (LRS). Using ¹H magnetic resonance (MR) methods, whole body adiposity, intrahepatocellular lipids (IHCL) and intramyocellular lipids (IMCL) were measured. Manganese-enhanced MRI (MEMRI) was used to investigate neuronal activity in hypothalamic regions involved in appetite control when fed ad libitum. At the end of the interventional period, adipocytes were isolated from epididymal adipose tissue and fasting plasma collected for hormonal and adipokine measurement. Mice on the HRS and LRS diet had similar body weights although total body adiposity, subcutaneous and visceral fat, IHCL, plasma leptin, plasma adiponectin plasma insulin/glucose ratios was significantly greater in the latter group. Adipocytes isolated from the LRS group were significantly larger and had lower insulin-stimulated glucose uptake. MEMRI data obtained from the ventromedial and paraventricular hypothalamic nuclei suggests a satiating effect of the HRS diet despite a lower energy intake.

Conclusion and Significance

Dietary RS significantly impacts on adipose tissue patterning, adipocyte morphology and metabolism, glucose and insulin metabolism, as well as affecting appetite regulation, supported by changes in neuronal activity in hypothalamic appetite regulation centres which are suggestive of satiation.     

Adipose Tissue Distribution Predicts Survival in Amyotrophic Lateral Sclerosis

Background

amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that leads to death within a few years after diagnosis. Malnutrition and weight loss are frequent and are indexes of poor prognosis. Total body fat and fat distribution have not been studied in ALS patients.

Objectives

Our aim was to describe adipose tissue content and distribution in ALS patients.

Design

We performed a cross-sectional study in a group of ALS patients (n = 62, mean disease duration 22 months) along with age and gender matched healthy controls (n = 62) using a MRI-based method to study quantitatively the fat distribution.

Results

Total body fat of ALS patients was not changed as compared with controls. However, ALS patients displayed increased visceral fat and an increased ratio of visceral to subcutaneous fat. Visceral fat was not correlated with clinical severity as judged using the ALS functional rating scale (ALS-FRS-R), while subcutaneous fat in ALS patients correlated positively with ALS-FRS-R and disease progression. Multiple regression analysis showed that gender and ALS-FRS-R, but not site of onset, were significant predictors of total and subcutaneous fat. Increased subcutaneous fat predicted survival in male patients but not in female patients (p<0.05).

Conclusions

Fat distribution is altered in ALS patients, with increased visceral fat as compared with healthy controls. Subcutaneous fat content is a predictor of survival of ALS patients.