Identification of potential obese-specific biomarkers and pathways associated with abdominal subcutaneous fat deposition in pig using a comprehensive bioinformatics strategy.

Abdominal subcutaneous fat deposition (ASFD) is not only related to meat quality in the pig industry but also to human health in medicine. It is of great value to elucidate the potential molecular mechanisms of ASFD. The present study aims to identify obese-specific biomarkers and key pathways correlated with ASFD in pigs. The ASF-related mRNA expression dataset GSE136754 was retrieved from the Gene Expression Omnibus (GEO) database and systematically analyzed using a comprehensive bioinformatics method. A total of 565 differentially expressed genes (DEGs) were identified between three obese and three lean pigs, and these DEGs were mainly involved in the p53 signaling pathway, MAPK signaling pathway and fatty acid metabolism. A protein-protein interaction (PPI) network, consisting of 540 nodes and 1,065 edges, was constructed, and the top ten genes with the highest degree scores-ABL1, HDAC1, CDC42, HDAC2, MRPS5, MRPS10, MDM2, JUP, RPL7L1 and UQCRFS1-were identified as hub genes in the whole PPI network. Especially HDAC1, MDM2, MRPS10 and RPL7L1 were identified as potential robust obese-specific biomarkers due to their significant differences in single gene expression levels and high ROC area; this was further verified by quantitative real-time PCR (qRT-PCR) on abdominal subcutaneous fat samples from obese-type (Saba) and lean-type (Large White) pigs. Additionally, a mRNA-miRNA-lncRNA ceRNA network consisting of four potential biomarkers, 15 miRNAs and 51 lncRNAs was established, and two targeted lncRNAs with more connections, XIST and NEAT1, were identified as potentially important regulatory factors. The findings of this study may provide novel insights into the molecular mechanism involved in ASFD.

Abdominal subcutaneous fat thickness combined with a 50-g glucose challenge test at 24-28 weeks of pregnancy in predicting gestational diabetes mellitus.

BACKGROUND: This investigation aimed to analyse the efficacy of abdominal subcutaneous fat thickness (ASFT) value >18.1 mm combined with a 50-g glucose challenge test (GCT) between 24-28 weeks of gestation in predicting gestational diabetes mellitus (GDM) cases. METHODS: This cross-sectional study was carried out from February 2021 to December 2022. All pregnant women received a 50-g GCT at 24-28 weeks of pregnancy for the GDM screening. Pregnant women with a blood glucose value between 140-190 mg/dl experienced 100 g OGTT. Even if 50-g GCT was normal, 100-g OGTT was offered to patients with an ASFT value above 18.1 mm. RESULTS: Among the 728 pregnant women we enrolled, 154 (21.2%) cases were screened as positive. The number of patients who first screened positive and determined to be GDM after the 100-g oral glucose tolerance test (OGTT) was 43 (5.9%). A total of 67 cases (9.2%) had an ASFT measurement above 18.1 mm. Two cases with a negative 50-g GCT and ASFT <18.1 mm were diagnosed as GDM in the later weeks of pregnancy. A 50-g GCT combined with ASFT measurement above 18.1 mm predicted GDM with a sensitivity of 87.9%, a specificity of 88.7%, a positive predictive value (PPV) of 36.0%, and a negative PV (NPV) of 99.7%. CONCLUSIONS: A 50-g GCT combined with ASFT measurement that can be easily and accurately obtained during routine antenatal care in the second trimester might be a beneficial indicator for predicting GDM cases.

Screening and diagnosing pregnant women at greater risk of developing gestational diabetes mellitus are crucial to enhancing short- and long-term outcomes of the mother and foetus. An accurate diagnosis could provide proper treatment, which could be dietary or pharmacological, manage the disease, and improve pregnancy outcomes. In the current study, we revealed that gestational diabetes was predicted with high sensitivity and specificity in pregnant women with a 50-gram glucose challenge test and abdominal subcutaneous fat thickness measurement above 18.1 millimetres. Therefore, abdominal subcutaneous fat thickness measurement is anticipated to be extensively used as an indicative variable for predicting gestational diabetes mellitus cases during the second trimester of pregnancy.

Induction of fat apoptosis by a combination of synchronized radiofrequency and HIFEM technology: Human histology study.

PURPOSE: With the growing demand for more effective fat reduction techniques, a combination of synchronized radiofrequency (RF) and HIFEM has been introduced. Preceding studies evidenced the ability of RF+HIFEM to maintain the fat tissue temperature at the levels necessary for adipocyte apoptosis while documenting the induced changes to the fat tissue during the several weeks after the treatment. This study aims to demonstrate the induction of apoptosis by RF+HIFEM technology in the early stages through the assessment of caspase-3 protein, one of the apoptosis-executing proteases. DESIGN: In this two-arm, single-center, randomized trial, nine human subjects were enrolled and assigned into two groups, either the active group (N = 6) treated with both RF+HIFEM set at the highest tolerated levels or the sham group (N = 3) treated with 5% of the maximum RF+HIFEM power, serving as a control. All patients were scheduled to undergo one treatment visit of the abdominal area, two follow-up visits at 8 and 24 h, and one safety visit 7 days after the treatment. A punch biopsy (5 mm in diameter, approximately 10 mm in depth) was obtained from the abdominal area at the baseline and consecutive follow-up visits. Samples were fixed, and cut into 5 µm thick slices, and immunohistochemical staining was used to visualize the Caspase-3, revealing the adipocyte nuclei where apoptosis processes are in progress. FINDINGS: Documented findings suggest that the temperature threshold of 43-45°C is required to initiate fat apoptosis and consequent reduction in adipocyte number was achieved during the combined treatment with RF+HIFEM. The active group showed an elevated ratio of positively stained nuclei versus all adipocyte nuclei found on the evaluated slices-referred to as the apoptotic index (AI). The AI significantly (p < 0.001) increased at both 8 h (47.01 ± 10.56%) and 24 h (43.58 ± 6.35%) posttreatment. The Sham group showed no significant change in the AI (p > 0.05). No adverse events or side effects related to the treatments were observed. SUMMARY: This study supports previously published evidence on fat reduction after RF+HIFEM treatment, documenting the safe initiation of adipocyte programmed cell death posttreatment.

Sex-specific association of visceral and subcutaneous adipose tissue volumes with systemic inflammation and innate immune cells in people living with obesity.

BACKGROUND AND AIMS: Obesity predisposes to metabolic and cardiovascular diseases. Adipose tissue inflammation and systemic inflammation contribute to these complications. There are strong sex differences in adipose tissue distribution and in systemic inflammation. Women have more subcutaneous adipose tissue (SAT) and less visceral adipose tissue (VAT) than men. We explored the sex differences in the association between the different adipose compartments and inflammatory markers that are important in cardiometabolic disease pathophysiology. METHODS: Single-center observational cohort study with 302 individuals with a BMI ≥ 27 kg/m2. We were unable to acquire MRI data from seven individuals and from another 18 the MRI data were not usable, resulting in 277 people (155 men, 122 women), aged 55-81 years. INTERVENTION: We performed the following measurements: abdominal magnetic resonance imaging to measure VAT, and SAT (deep and superficial) volumes; circulating leukocyte counts and cytokine production capacity of peripheral blood mononuclear cells (PBMCs), circulating cytokines, adipokines, and targeted proteomics; abdominal sSAT biopsies for histology and gene expression. RESULTS: Only in women, (s)SAT volume was associated with circulating leukocytes, monocytes, and neutrophils. Circulating IL-6 and IL-18BP were associated with SAT volume in women and VAT in men. Several circulating proteins, including monocyte-colony-stimulating factor 1 and hepatocyte growth factor, are associated with sSAT in women and VAT in men. Only in women, SAT volume is associated with SAT expression of inflammatory proteins, including leptin, CD68, TNFα and IL-1α. CONCLUSION: In women living with obesity, abdominal SAT volume, especially sSAT, is associated with circulating leukocytes and inflammatory proteins. In men, these parameters mainly show associations with VAT volume. This could be because only in women, sSAT volume is associated with sSAT expression of inflammatory proteins. These findings underscore that future research on adipose tissue in relation to cardiometabolic and cardiovascular disease should take sex differences into account.

A fully convolutional neural network for comprehensive compartmentalization of abdominal adipose tissue compartments in MRI.

BACKGROUND: Existing literature has highlighted structural, physiological, and pathological disparities among abdominal adipose tissue (AAT) sub-depots. Accurate separation and quantification of these sub-depots are crucial for advancing our understanding of obesity and its comorbidities. However, the absence of clear boundaries between the sub-depots in medical imaging data has challenged their separation, particularly for internal adipose tissue (IAT) sub-depots. To date, the quantification of AAT sub-depots remains challenging, marked by a time-consuming, costly, and complex process. PURPOSE: To implement and evaluate a convolutional neural network to enable granular assessment of AAT by compartmentalization of subcutaneous adipose tissue (SAT) into superficial subcutaneous (SSAT) and deep subcutaneous (DSAT) adipose tissue, and IAT into intraperitoneal (IPAT), retroperitoneal (RPAT), and paraspinal (PSAT) adipose tissue. MATERIAL AND METHODS: MRI datasets were retrospectively collected from Singapore Preconception Study for Long-Term Maternal and Child Outcomes (S-PRESTO: 389 women aged 31.4 ± 3.9 years) and Singapore Adult Metabolism Study (SAMS: 50 men aged 28.7 ± 5.7 years). For all datasets, ground truth segmentation masks were created through manual segmentation. A Res-Net based 3D-UNet was trained and evaluated via 5-fold cross-validation on S-PRESTO data (N = 300). The model's final performance was assessed on a hold-out (N = 89) and an external test set (N = 50, SAMS). RESULTS: The proposed method enabled reliable segmentation of individual AAT sub-depots in 3D MRI volumes with high mean Dice similarity scores of 98.3%, 97.2%, 96.5%, 96.3%, and 95.9% for SSAT, DSAT, IPAT, RPAT, and PSAT respectively. CONCLUSION: Convolutional neural networks can accurately sub-divide abdominal SAT into SSAT and DSAT, and abdominal IAT into IPAT, RPAT, and PSAT with high accuracy. The presented method has the potential to significantly contribute to advancements in the field of obesity imaging and precision medicine.

Machine Learning-Based Prediction of Abdominal Subcutaneous Fat Thickness During Pregnancy.

Objective: Current evidence regarding the safety of abdominal subcutaneous injections in pregnant women is limited. In this study, we developed a predictive model for abdominal skin-subcutaneous fat thickness (S-ScFT) by gestational periods (GP) in pregnant women. Methods: A total of 354 cases were measured for S-ScFT. Three machine learning algorithms, namely deep learning, random forest, and support vector machine, were used for S-ScFT predictive modeling and factor analysis for each abdominal site. Data analysis was performed using SPSS and RapidMiner softwares. Results: The deep learning algorithm best predicted the abdominal S-ScFT. The common important variables in all three algorithms for the prediction of abdominal S-ScFT were menarcheal age, prepregnancy weight, prepregnancy body mass index (categorized), large fetus for gestational age, and alcohol consumption. Conclusion: Predicting the safety of subcutaneous injections during pregnancy could be beneficial for managing gestational diabetes mellitus in pregnant women.

Diet composition, nutrient substitutions and circulating fatty acids in relation to ectopic and visceral fat depots.

BACKGROUND & AIMS: Short-term randomized trials have demonstrated that replacing saturated fat (SFA) with polyunsaturated fat (PUFA) causes a reduction or prevention of liver fat accumulation, but population-based studies on diet and body fat distribution are limited. We investigated cross-sectional associations between diet, circulating fatty acids and liver fat, visceral adipose tissue (VAT), intermuscular adipose tissue (IMAT) and other fat depots using different energy-adjustment models. METHODS: Sex-stratified analyses of n = 9119 (for serum fatty acids) to 13 849 (for nutrients) participants in UK Biobank were conducted. Fat depots were assessed by MRI, circulating fatty acids by NMR spectroscopy and diet by repeated 24-h recalls. Liver fat, VAT and IMAT were primary outcomes; total adipose tissue (TAT) and abdominal subcutaneous adipose tissue (ASAT) were secondary outcomes. Three a priori defined models were constructed: the all-components model, standard model and leave-one-out model (main model including specified nutrient substitutions). Imiomics (MRI-derived) was used to confirm and visualize associations. RESULTS: In women, substituting carbohydrates and free sugars with saturated fat (SFA) was positively associated with liver fat (ß (95% CI) = 0.19 (0.02, 0.36) and ß (95% CI) = 0.20 (0.05-0.35), respectively) and IMAT (ß (95% CI) = 0.07 (0.00, 0.14) and ß (95% CI) = 0.08 (0.02, 0.13), respectively), whereas substituting animal fat with plant fat was inversely associated with IMAT, ASAT and TAT. In the all-components and standard models, SFA and animal fat were positively associated with liver fat, IMAT and VAT whereas plant fat was inversely associated with IMAT in women. Few associations were observed in men. Circulating polyunsaturated fatty acids (PUFA) were inversely associated with liver fat, IMAT and VAT in both men and women, whereas SFA and monounsaturated fatty acids were positively associated. CONCLUSIONS: Type of dietary fat may be an important determinant of ectopic fat in humans consuming their habitual diet. Plant fat and PUFA should be preferred over animal fat and SFA. This is corroborated by circulating fatty acids and overall consistent through different energy adjustment models. TWITTER SUMMARY: In UK Biobank, intake of saturated- and animal fat were positively whereas biomarkers of polyunsaturated fat were inversely associated with liver-, visceral- and intermuscular fat. Type of dietary fat may be a determinant of ectopic fat, a risk factor for cardiometabolic disease.

Resistance training decreased abdominal adiposity in postmenopausal women.

OBJECTIVE: To investigate if abdominal adipose tissue volumes and ratios change after a 15-week structured resistance training intervention in postmenopausal women with vasomotor symptoms (VMS). STUDY DESIGN: Sixty-five postmenopausal women with VMS and low physical activity were randomized to either three days/week supervised resistance training or unchanged physical activity for 15 weeks. Women underwent clinical anthropometric measurements and magnetic resonance imaging (MRI) at baseline and after 15 weeks. MRI was done using a Philips Ingenia 3.0 T MR scanner (Philips, Best, The Netherlands). The per protocol principle was used in the analysis of data. MAIN OUTCOME MEASUREMENTS: The absolute change from baseline to week 15 in visceral adipose tissue (VAT) volume and the relative ratio (VAT ratio) between VAT and total abdominal adipose tissue (TAAT), i.e. the sum of abdominal subcutaneous adipose tissue (ASAT) and VAT. RESULTS: There were no significant differences between the groups in characteristics, anthropometry or MRI measures at baseline. Women who were compliant with the intervention (i.e. participated in at least two of the three scheduled training sessions per week) had significantly different reduction over time in ASAT (p = 0.006), VAT (p = 0.002), TAAT (p = 0.003) and fat ratio (p < 0.001) compared with women in the control group. CONCLUSIONS: Implementation of a 15-week resistance training regimen in midlife may help women to counteract the abdominal fat redistribution associated with the menopausal transition. CLINICAL TRIALS: gov registered ID: NCT01987778.

Sex-specific Association Between Adipose Tissue Inflammation and Vascular and Metabolic Complications of Obesity.

CONTEXT: Adipose tissue (AT) inflammation predisposes to insulin resistance and metabolic syndrome in obesity. OBJECTIVE: To investigate the association between adipocyte size, AT inflammation, systemic inflammation, and metabolic and atherosclerotic complications of obesity in a sex-specific manner. DESIGN: Cross-sectional cohort study. SETTING: University hospital in the Netherlands. PARTICIPANTS: A total of 302 adult subjects with a body mass index (BMI) ≥ 27 kg/m2. MAIN OUTCOME MEASURES: We obtained subcutaneous abdominal fat biopsies and systematically assessed, in a sex-specific manner, associations of several parameters of AT inflammation (including adipocyte size, macrophage content, crown-like structures, and gene expression) to biomarkers of systemic inflammation, leukocyte number and function, and to the presence of metabolic syndrome, insulin resistance, and carotid atherosclerotic plaques, assessed with ultrasound. RESULTS: Adipocyte size was associated with metabolic syndrome and AT macrophage content with insulin resistance. In contrast, none of the AT parameters was associated with carotid atherosclerosis, although mRNA expression of the anti-inflammatory IL-37 was associated with a lower intima-media thickness. We revealed profound sex-specific differences, with an association between BMI and adipocyte size, and between adipocyte size and metabolic syndrome in men only. Also, only men showed an association between adipocyte size, AT expression of leptin and MCP-1, and AT macrophage numbers, and between AT inflammation (crown-like structure number) and several circulating inflammatory proteins, including high specificity C-reactive protein, and IL-6. CONCLUSIONS: Inflammation in abdominal subcutaneous adipose tissue is more related to the metabolic than the atherosclerotic complications of obesity, and there are profound sex-specific differences in the association between BMI, adipocyte size, AT inflammation, and systemic inflammation, which are much stronger in men than women.

Phenotypic and functional features of B cells from two different human subcutaneous adipose depots.

In this study, we have compared frequencies, phenotype, function and metabolic requirements of B cells isolated from the breast and abdominal subcutaneous adipose tissue (AT) of women with obesity who underwent weight reduction surgeries. Results show that B cells from the abdominal AT are more inflammatory than those from the breast, characterized by higher frequencies of inflammatory B cell subsets and higher expression of RNA for inflammatory markers associated with senescence. Secretion of autoimmune antibodies is also higher in the abdominal AT as compared to the breast, and is associated with higher frequencies of autoimmune B cells with the membrane phenotype CD21lowCD95+ B cells expressing the transcription factor T-bet. Moreover, glucose uptake is higher in B cells from the abdominal AT as compared to the breast, thereby suggesting a better capacity to perform glycolysis, needed to support intrinsic B cell inflammation and autoimmune antibody secretion.

Differences in metabonomic profiles of abdominal subcutaneous adipose tissue in women with polycystic ovary syndrome.

Introduction: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder that often coexists with a metabolic disorder. Studies have demonstrated that the malfunction of adipose tissue, particularly abdominal adipose tissue, could exacerbate reproductive and metabolic problems in PCOS patients. Adipose tissue-secreted signaling mediators (e.g., lipids and metabolites) would then interact with other body organs, including the ovary, to maintain the systemic equilibrium. Methods: In this study, we examined adipose samples from PCOS patients and unaffected individuals using a liquid chromatography-mass spectrometry-based metabonomics approach (LC-MS/MS). PCOS biomarkers were selected using multivariate statistical analysis. Results: Our pathway analysis revealed that these differential metabolites could be engaged in inflammatory diseases and mitochondrial beta-oxidation. We further developed an in vitro PCOS cell model to examine the effects of hyperandrogenism on granulosa cells and related metabolic disorders. We noted that isoleucine recovered the promotive effect on cell apoptosis, inhibitory effect on cell proliferation, sex hormone secretion, and mitochondrial function induced by dehydroepiandrosterone. Our gas chromatography-mass spectrometry targeted analysis (GC-MS/MS) revealed that isoleucine was significantly decreased in PCOS patients. Discussion: Based on these results, we speculate that metabolome alterations are vital in ameliorating PCOS symptoms. This may be a novel therapeutic target for PCOS treatment. Our study provides preliminary evidence that these findings will enhance our ability to accurately diagnose and intervene in PCOS.

Sex-specific equations to estimate body composition: Derivation and validation of diagnostic prediction models using UK Biobank.

BACKGROUND & AIMS: Body mass index and waist circumference are simple measures of obesity. However, they do not distinguish between visceral and subcutaneous fat, or muscle, potentially leading to biased relationships between individual body composition parameters and adverse health outcomes. The purpose of this study was to develop and validate prediction models for volumetric adipose and muscle. METHODS: Based on cross-sectional data of 18,457, 18,260, and 17,052 White adults from the UK Biobank, we developed sex-specific equations to estimate visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (ASAT), and total thigh fat-free muscle (FFM) volumes, respectively. Volumetric magnetic resonance imaging served as the reference. We used the least absolute shrinkage and selection operator and the extreme gradient boosting methods separately to fit three sequential models, the inputs of which included demographics and anthropometrics and, in some, bioelectrical impedance analysis parameters. We applied comprehensive metrics to assess model performance in the temporal validation set. RESULTS: The equations that included more predictors generally performed better. Accuracy of the equations was moderate for VAT (percentage of estimates that differed <30% from the measured values, 70 to 78 in males, 64 to 69 in females) and good for ASAT (85 to 91 in males, 90 to 95 in females) and FFM (99 to 100 in both sexes). All the equations appeared precise (interquartile range of the difference, 0.89 to 1.76 L for VAT, 1.16 to 1.61 L for ASAT, 0.81 to 1.39 L for FFM). Bias of all the equations was negligible (-0.17 to 0.05 L for VAT, -0.10 to 0.12 L for ASAT, -0.07 to 0.09 L for FFM). The equations achieved superior cardiometabolic correlations compared with body mass index and waist circumference. CONCLUSIONS: The developed equations to estimate VAT, ASAT, and FFM volumes achieved moderate to good performance. They may be cost-effective tools to revisit the implications of diverse body components.

Ultrasound-guided percutaneous core needle biopsy of abdominal subcutaneous fat for diagnosing amyloidosis: comparison with bone marrow biopsy.

BACKGROUND: Patients with underlying hematologic malignancy have a higher risk of developing systemic amyloidosis, which worsens their prognosis. Histopathologic detection of amyloid deposits in tissue biopsy specimens is the only diagnostic method for amyloidosis. PURPOSE: To compare the efficacy of ultrasound-guided percutaneous core needle biopsy (USPCB) of abdominal subcutaneous fat with that of bone marrow biopsy (BMB) for diagnosing amyloidosis. MATERIAL AND METHODS: A total of 90 consecutive patients with underlying hematologic disorders who underwent both USPCB of abdominal subcutaneous fat and BMB for suspicion of amyloid deposition during a 10-year period were included in this retrospective study. RESULTS: The sensitivity and specificity of detecting amyloid deposition were 85.7% and 100%, respectively, with USPCB as opposed to 4.8% and 100%, respectively, with BMB, and the sensitivity was significantly higher with USPCB (P < 0.001). The mean number of times USPCB was performed was 3.3. There were no major complications associated with USPCB. The sensitivity of detecting amyloidosis was not different between the 18-G needle group and the 14-G group (100% vs. 80%; P = 0.623). Logistic regression analysis revealed that acquiring more cores from USPCB and thinner fat tissues were statistically significant factors that affected the diagnostic accuracy of USPCB for amyloid detection. CONCLUSION: The sensitivity of amyloid deposition was significantly higher with USPCB of abdominal subcutaneous fat than BMB. Acquiring more cores by multiple biopsies instead of using a larger bore needle and thin subcutaneous fat pad may be a favorable factor for the diagnostic accuracy of USPCB.

Changes in subcutaneous adipose tissue microRNA expression in response to exercise training in obese African women.

The mechanisms that underlie exercise-induced adaptations in adipose tissue have not been elucidated, yet, accumulating studies suggest an important role for microRNAs (miRNAs). This study aimed to investigate miRNA expression in gluteal subcutaneous adipose tissue (GSAT) in response to a 12-week exercise intervention in South African women with obesity, and to assess depot-specific differences in miRNA expression in GSAT and abdominal subcutaneous adipose tissue (ASAT). In addition, the association between exercise-induced changes in miRNA expression and metabolic risk was evaluated. Women underwent 12-weeks of supervised aerobic and resistance training (n = 19) or maintained their regular physical activity during this period (n = 12). Exercise-induced miRNAs were identified in GSAT using Illumina sequencing, followed by analysis of differentially expressed miRNAs in GSAT and ASAT using quantitative real-time PCR. Associations between the changes (pre- and post-exercise training) in miRNA expression and metabolic parameters were evaluated using Spearman's correlation tests. Exercise training significantly increased the expression of miR-155-5p (1.5-fold, p = 0.045), miR-329-3p (2.1-fold, p < 0.001) and miR-377-3p (1.7-fold, p = 0.013) in GSAT, but not in ASAT. In addition, a novel miRNA, MYN0617, was identified in GSAT, with low expression in ASAT. The exercise-induced differences in miRNA expression were correlated with each other and associated with changes in high-density lipoprotein concentrations. Exercise training induced adipose-depot specific miRNA expression within subcutaneous adipose tissue depots from South African women with obesity. The significance of the association between exercise-induced miRNAs and metabolic risk warrants further investigation.

Reply: New alternatives in body composition assessment techniques.

Undoubtedly, ultrasound measurement of fat thickness and A/G ratio could provide a practical solution in places where DXA is unavailable. Still, it possesses several challenges due to diverse corporal compositions, especially in the measure of fat thickness in overweight or obese patients. In addition, those patients tend to have a sizeable abdominal diameter, so visualizing the aorta could be challenging; despite this technical factor, ultrasound often results be accurate and reliable, as should be expected from a suitable measurement technique for abdominal subcutaneous fat. It would be interesting to compare other body composition assessment techniques, such as MRI, which has excellent agreement with DXA without the ionizing radiation or compare it to computed tomography that can accurately determine fat in skeletal muscle tissue and the liver.

Cryolipolysis for abdominal subcutaneous fat reduction: A prospective, multicenter, single arm, clinical study.

Various treatment methods are used for noninvasive body contouring. To evaluate the efficacy and safety of a newly designed cryolipolysis device using a three-dimensional cooling method for abdominal fat reduction. Twenty-five participants with clinically apparent abdominal fat tissue participated in the study. The thickness of fat tissue below the umbilicus level was measured using a caliper at baseline and 12 weeks after the first treatment. The height of abdominal subcutaneous fat tissue on ultrasonography and participant satisfaction were assessed at every visit for 16 weeks. All adverse events (AEs) during the study period were recorded. p values <0.05 were considered statistically significant. Twenty-four participants completed this study; the mean BMI of participants was 29.34 ± 2.36 kg/m2 . The mean thickness of abdominal subcutaneous fat was significantly lower at 12 weeks (40.4 ± 6.8 mm, p < 0.001) than at baseline (49.3 ± 8.5 mm). Differences in the height of abdominal subcutaneous fat compared to that at baseline were 1.02 ± 0.41 cm (12 weeks, p < 0.001) and 1.13 ± 0.44 cm (16 weeks, p < 0.001). Rates of abdominal subcutaneous fat reduction at 12 and 16 weeks compared to that at baseline were 28.45% and 31.13%, respectively. The ratio of abdominal circumference to hip circumference at 12 and 16 weeks was significantly decreased compared to that at baseline. Most participants (95.8%) reported improvement in satisfaction scores at 16 weeks. There were no serious AEs during the entire study period. The study demonstrated the efficacy of a noninvasive cryolipolysis device using a three-dimensional cooling method for reducing abdominal subcutaneous fat.

One week of overeating upregulates angiogenic and lipolytic gene expression in human subcutaneous adipose tissue from exercise trained and untrained adults.

Effective storage of excess energy in abdominal subcutaneous adipose tissue during periods of overeating may help attenuate weight-gain-related insulin resistance. The objective of this study was to assess changes in the expression of factors regulating abdominal subcutaneous adipose tissue storage capacity in response to a brief exposure to overeating in nonobese adults. Because exercise can alter the expression of genes involved in regulating adipose tissue storage capacity, we compared the responses to overeating in regular exercisers (EX, n = 11) and nonexercisers (nonEX, n = 11). Abdominal subcutaneous adipose tissue samples and oral glucose tolerance tests were performed before and after participants ate 30% above their estimated daily energy requirements for 1 week. Both EX and nonEX gained ∼1 kg (P < 0.01), and Matsuda insulin sensitivity index was reduced ∼15% (P = 0.04) in both groups. Gene expression of factors involved in lipid metabolism (HSL, ATGL, DGAT, and PPARγ) and angiogenesis (HIF1α and KDR) were increased (P < 0.05), with no differences observed between EX and nonEX. In contrast, protein abundance of these factors did not change. The modest overeating stimulus did not increase markers of inflammation in the systemic circulation or adipose tissue. Overall, our findings indicate that a brief and modest overeating stimulus can impair insulin sensitivity and upregulate genes involved in abdominal adipose tissue storage capacity similarly in exercisers and nonexercisers. ClinicalTrials.gov ID#: NCT02701738.

A pilot investigation of genetic and epigenetic variation of FKBP5 and response to exercise intervention in African women with obesity.

We investigated gluteal (GSAT) and abdominal subcutaneous adipose tissue (ASAT) DNA methylation of FKBP5 in response to a 12-week intervention in African women with obesity, as well as the effect of the rs1360780 single nucleotide polymorphism (SNP) on FKBP5 methylation, gene expression and post-exercise training adaptations in obesity and metabolic related parameters. Exercise (n = 19) participants underwent 12-weeks of supervised aerobic and resistance training while controls (n = 12) continued their usual behaviours. FKBP5 methylation was measured in GSAT and ASAT using pyrosequencing. SNP and gene expression analyses were conducted using quantitative real-time PCR. Exercise training induced FKBP5 hypermethylation at two CpG dinucleotides within intron 7. When stratified based on the rs1360780 SNP, participants with the CT genotype displayed FKBP5 hypermethylation in GSAT (p < 0.05), and ASAT displayed in both CC and CT carriers. CC allele carriers displayed improved cardiorespiratory fitness, insulin sensitivity, gynoid fat mass, and waist circumference (p < 0.05) in response to exercise training, and these parameters were attenuated in women with the CT genotype. These findings provide a basis for future studies in larger cohorts, which should assess whether FKBP5 methylation and/or genetic variants such as the rs1360780 SNP could have a significant impact on responsiveness to exercise interventions.

Levels of abdominal adipose tissue and metabolic-associated fatty liver disease (MAFLD) in middle age according to average fast-food intake over the preceding 25 years: the CARDIA Study.

BACKGROUND: Higher levels of intra-abdominal adipose tissue (IAAT) comprising visceral adipose tissue (VAT), intermuscular adipose tissue (IMAT), and liver fat are posited drivers of obesity-related chronic disease risk. Fast food is hypothesized to contribute to IAAT patterns. OBJECTIVES: We quantified levels of abdominal subcutaneous adipose tissue (SAT), IAAT, and odds of metabolic-associated fatty liver disease (MAFLD) in middle age according to average fast-food intake over the preceding 25 y. METHODS: We analyzed data from the Coronary Artery Risk Development in Young Adults (CARDIA) study. Participants underwent 6 clinical exams and measurements over 25 y with computed tomography-measured VAT, SAT, and IMAT (n = 3156), plus MAFLD defined by liver attenuation (≤40 Hounsfield units) and 1 metabolic abnormality at year 25 (2010, n = 3001, n cases = 302). We estimated means of VAT, SAT, IMAT, and liver attenuation at the year 25 exam according to categories of average fast-food intake over the previous 25 y adjusted for sociodemographic and lifestyle factors and logistic regression to estimate the odds ratio of MAFLD at year 25. RESULTS: With higher average fast-food intake over 25 y (categorized as follows: never-1×/mo, >1×-3×/mo, 1-<2×/wk, 2-<3×/wk, ≥3×/wk), there were monotonic higher levels of VAT (98.5, 127.6, 134.5, 142.0, 145.5 cm3), P-trend < 0.0001, which were consistent across anthropometrically classified obesity categories. There was a similar pattern with liver fat. There were higher levels of IMAT and SAT with higher fast-food intake (P-trend = 0.003, 0.0002, respectively), with amounts leveling off at ≥2×/wk. In addition, compared with participants who ate fast food never-1×/mo, there were monotonic higher odds of having MAFLD at year 25 with higher average fast-food intake, with participants who ate fast food ≥3×/wk having an OR of MAFLD = 5.18 (95% CI: 2.87, 9.37). CONCLUSIONS: There were monotonic higher levels of VAT, liver fat, and odds of having MAFLD in middle age according to higher average fast-food intake over the preceding 25 y.

Efficacy of a Novel Injection Lipolysis to Induce Targeted Adipocyte Apoptosis: A Randomized, Phase IIa Study of CBL-514 Injection on Abdominal Subcutaneous Fat Reduction.

BACKGROUND: CBL-514 is a novel injectable drug that may be safe and efficacious for localized abdominal subcutaneous fat reduction. OBJECTIVES: The aim of this study was to assess the safety and efficacy of CBL-514 in reducing abdominal subcutaneous fat volume and thickness. METHODS: This Phase IIa, open-label, random allocation study consisted of a 6-week treatment period and follow-up at 4 and 8 weeks following the last treatment. Participants were randomly allocated to receive 1.2 mg/cm2 (180 mg), 1.6 mg/cm2 (240 mg), or 2.0 mg/cm2 (300 mg) of CBL-514 with up to 4 treatments, each comprising 60 injections into the abdominal adipose layer. Changes in abdominal subcutaneous fat were assessed by ultrasound at follow-up visits. Treatment-emergent adverse events were recorded. RESULTS: Higher doses of CBL-514 (unit dose, 2.0 and 1.6 mg/cm2) significantly improved the absolute and percentage reduction in abdominal fat volume (P < 0.00001) and thickness (P < 0.0001) compared with baseline. Although the COVID-19 pandemic halted some participant recruitment and follow-ups, analysis was unaffected, even after sample size limitations. CONCLUSIONS: CBL-514 injection at multiple doses up to 300 mg with a unit dose of 2.0 mg/cm2 is safe, well-tolerated, and reduced abdominal fat volume and thickness by inducing adipocyte apoptosis. Although other procedures exist to treat abdominal fat, they have limitations and may cause complications. At a dose of 2.0 mg/cm2, CBL-514 safely and significantly reduced abdominal fat volume by 24.96%, making it a promising new treatment for routine, nonsurgical abdominal fat reduction in dermatologic clinics.