Single-cell sequencing of human white adipose tissue identifies new cell states in health and obesity.

White adipose tissue (WAT) is an essential regulator of energy storage and systemic metabolic homeostasis. Regulatory networks consisting of immune and structural cells are necessary to maintain WAT metabolism, which can become impaired during obesity in mammals. Using single-cell transcriptomics and flow cytometry, we unveil a large-scale comprehensive cellular census of the stromal vascular fraction of healthy lean and obese human WAT. We report new subsets and developmental trajectories of adipose-resident innate lymphoid cells, dendritic cells and monocyte-derived macrophage populations that accumulate in obese WAT. Analysis of cell-cell ligand-receptor interactions and obesity-enriched signaling pathways revealed a switch from immunoregulatory mechanisms in lean WAT to inflammatory networks in obese WAT. These results provide a detailed and unbiased cellular landscape of homeostatic and inflammatory circuits in healthy human WAT.

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.

Biological Determinants of Metabolic Syndrome in Visceral and Subcutaneous Adipose Tissue from Severely Obese Women.

The metabolic syndrome (MetS) is a cluster of the most dangerous heart attack risk factors: diabetes or raised fasting plasma glucose, abdominal obesity, high cholesterol and high blood pressure. The goal of this study is to compare the state of the main features of obesity-associated white adipose tissue (WAT) dysfunction in 66 women with severe obesity without (MetS-) or with MetS (MetS+). Fat cell area, adipocyte size distribution and histological fibrosis were analysed in visceral (VAT) and abdominal subcutaneous WAT (SAT) in 33 age- and BMI-matched pairs of MetS- and MetS+ subjects. The mRNA expression of 93 genes implicated in obesity-associated WAT dysfunction was analysed by RT-qPCR in both fat depots. MetS+ females showed higher adipocyte hypertrophy in both fat depots and increased fibrosis and expression of macrophage and hypoxia markers in SAT. Transcriptional data suggest increased fatty acid oxidation in SAT and impaired thermogenesis and extracellular matrix remodelling in VAT from MetS+ subjects. A sPLS-DA model, including SAT expression of PPARA and LEPR genes identified MetS with an AUC = 0.87. Despite equal age, BMI and body composition, MetS+ females display morphological and transcriptional differences in both WAT depots, especially in SAT. These factors may contribute to the transition to MetS.

Phases of Metabolic and Soft Tissue Changes in Months Preceding a Diagnosis of Pancreatic Ductal Adenocarcinoma.

BACKGROUND & AIMS: Identifying metabolic abnormalities that occur before pancreatic ductal adenocarcinoma (PDAC) diagnosis could increase chances for early detection. We collected data on changes in metabolic parameters (glucose, serum lipids, triglycerides; total, low-density, and high-density cholesterol; and total body weight) and soft tissues (abdominal subcutaneous fat [SAT], adipose tissue, visceral adipose tissue [VAT], and muscle) from patients 5 years before the received a diagnosis of PDAC. METHODS: We collected data from 219 patients with a diagnosis of PDAC (patients) and 657 healthy individuals (controls) from the Rochester Epidemiology Project, from 2000 through 2015. We compared metabolic profiles of patients with those of age- and sex-matched controls, constructing temporal profiles of fasting blood glucose, serum lipids including triglycerides, cholesterol profiles, and body weight and temperature for 60 months before the diagnosis of PDAC (index date). To construct the temporal profile of soft tissue changes, we collected computed tomography scans from 68 patients, comparing baseline (>18 months before diagnosis) areas of SAT, VAT, and muscle at L2/L3 vertebra with those of later scans until time of diagnosis. SAT and VAT, isolated from healthy individuals, were exposed to exosomes isolated from PDAC cell lines and analyzed by RNA sequencing. SAT was collected from KRAS+/LSLG12D P53flox/flox mice with PDACs, C57/BL6 (control) mice, and 5 patients and analyzed by histology and immunohistochemistry. RESULTS: There were no significant differences in metabolic or soft tissue features of patients vs controls until 30 months before PDAC diagnosis. In the 30 to 18 months before PDAC diagnosis (phase 1, hyperglycemia), a significant proportion of patients developed hyperglycemia, compared with controls, without soft tissue changes. In the 18 to 6 months before PDAC diagnosis (phase 2, pre-cachexia), patients had significant increases in hyperglycemia and decreases in serum lipids, body weight, and SAT, with preserved VAT and muscle. In the 6 to 0 months before PDAC diagnosis (phase 3, cachexia), a significant proportion of patients had hyperglycemia compared with controls, and patients had significant reductions in all serum lipids, SAT, VAT, and muscle. We believe the patients had browning of SAT, based on increases in body temperature, starting 18 months before PDAC diagnosis. We observed expression of uncoupling protein 1 (UCP1) in SAT exposed to PDAC exosomes, SAT from mice with PDACs, and SAT from all 5 patients but only 1 of 4 controls. CONCLUSIONS: We identified 3 phases of metabolic and soft tissue changes that precede a diagnosis of PDAC. Loss of SAT starts 18 months before PDAC identification, and is likely due to browning. Overexpression of UCP1 in SAT might be a biomarker of early-stage PDAC, but further studies are needed.

Histological Analysis of the Effect of ATX-101 (Deoxycholic Acid Injection) on Subcutaneous Fat: Results From a Phase 1 Open-Label Study.

BACKGROUND: ATX-101 is approved for submental fat reduction. OBJECTIVE: To characterize the histological effect of ATX-101 injection into subcutaneous fat. METHODS: This Phase 1 open-label study enrolled 14 adults to receive injections of ATX-101 into abdominal fat at varying concentrations (0.5%, 1.0%, 2.0%, or 4.0%), volumes (0.2 or 0.4 mL), spacing (0.7, 1.0, or 1.5 cm), and time points before scheduled abdominoplasty (1, 3, 7, or 28 days). During abdominoplasty, tissue was excised and preserved for histology. RESULTS: All injection paradigms resulted in histological changes confined to the subcutaneous layer, which were more prominent at higher concentrations and independent of volume and spacing. Key features at Day 1 after injection were adipocytolysis, blood vessel injury, neutrophilic inflammation, and lysis of locally present neutrophils. At Day 3, inflammation was reduced versus Day 1, and hemorrhage and lipid lake formation (at higher concentrations) were observed. Day 7 samples exhibited prominent adipocytolysis, mild inflammation, lipid-laden macrophages in the septae, and repair of vascular injury. At Day 28, inflammation was largely resolved and prominent features were septal thickening, neovascularization, and atrophy of fat lobules. CONCLUSION: Subcutaneous injection of ATX-101 induces adipocytolysis and local inflammation with septal thickening and resolution of inflammation by 28 days after injection.

Increased maternal abdominal subcutaneous fat thickness and body mass index are associated with increased cesarean delivery: A prospective cohort study.

INTRODUCTION: Early pregnancy body mass index (BMI) is known to predict adverse pregnancy outcomes but does not account for body fat distribution. This study aimed to determine prospectively whether maternal abdominal subcutaneous fat thickness (SCFT) measured by ultrasound at the fetal morphology scan is a better predictor than BMI of mode of delivery and other pregnancy outcomes. MATERIAL AND METHODS: This was a prospective cohort study of women delivering singleton neonates at a tertiary public hospital. Women were included if they had appropriate images at the routine fetal anomaly ultrasound scan and delivered in the facility. The primary outcome was mode of delivery categorized as cesarean section or vaginal delivery. The relation between maternal SCFT and BMI was described using the Pearson correlation coefficient. The association of maternal abdominal SCFT BMI at booking-in was compared with pregnancy outcomes using univariate linear and logistic regression. RESULTS: SCFT and BMI were obtained for 997 women. The median (interquartile range) SCFT was 15.3 mm (12.8-19.6) and median (interquartile range) BMI 24.3 kg/m2 (21.7-28.3). Maternal abdominal SCFT and BMI were highly correlated (R2  = 0.55). Both were significantly associated with cesarean delivery: SCFT per 5 mm (odds ratio [OR] 1.32, 95% confidence interval (CI) 1.18-1.48; BMI per 5 kg/m2 OR 1.29, 95% CI 1.15-1.44. CONCLUSIONS: Maternal abdominal SCFT and BMI were both significantly associated with cesarean delivery and other outcomes. More research is needed to define the strengths of maternal SCFT in predicting pregnancy outcomes.

Numerical Study of Hyper-Thermic Laser Lipolysis With 1,064 nm Nd:YAG Laser in Human Subjects.

BACKGROUND AND OBJECTIVES: The aim of this study was to develop a numerical model for hyperthermic laser lipolysis in human subjects to improve understanding of the procedure and find optimal therapeutic parameters. STUDY DESIGN/MATERIALS AND METHODS: A numerical model of hyperthermic laser lipolysis (HTLL) on human subjects was developed that is based on light and heat transport, including the effects of blood perfusion and forced air cooling. Tissue damage was evaluated using the Arrhenius model. Three irradiation scenarios were considered: single skin area irradiation without and with forced air cooling, and sequential heating of four adjacent skin areas in a cyclical manner. An evaluation of the numerical model was made by comparing the recorded skin surface temperature evolution during an experimental HTLL procedure performed on the abdomen of ten human volunteers using a 1,064 nm Nd:YAG laser irradiation. RESULTS: A good agreement was obtained between the simulated skin surface temperatures and that as measured during the HTLL procedure. The temperature difference between the simulations and experiments was in the range of 0.2-0.4°C. The model parameters, which were fitted to the experiment were the perfusion parameter (0.36-0.79 and 0.18-0.49 kg/m 3 ·s for dermis and subcutis) and the subcutaneous tissue absorption coefficient (0.17-0.21 cm -1 ). By using the developed HTLL model and the determined parameters, temperature depth distributions and the resulting thermal injury to adipocytes were simulated under different treatment conditions. Optimal ranges of the HTTL treatment parameters were determined for different skin types, damaging adipocytes while preserving skin cells. The target subcutaneous temperatures were in the range of 43-47°C, which has been found to lead to programmed adipocyte death. The optimal treatment parameters were further used to define a range of recommended protocols for safe and effective multiarea cycled HTLL treatment of large body surfaces. Specifically, for the set of chosen optimal treatment parameters (4-5 treatment cycles, 1.2 W/cm 2 radiant exposure, and 60-130 W/cm 2 forced air heat-transfer coefficient) the threshold surface temperature during irradiation was found to be in the range of 31-38°C, depending on the skin type and heat-transfer coefficient. CONCLUSIONS: The developed numerical model allows for the calculation of the temperature distribution and the resulting injury to adipocyte cells within deeper lying fatty tissues under different clinical treatment conditions. It is demonstrated that by measuring the temporal evolution of the skin surface temperature and by stopping the laser irradiation at predefined skin surface threshold temperatures, it may be possible to monitor and control the effects of the HTLL procedure deeper within the tissue. As such, the model provides a better insight into the HTLL, and may become a tool for defining the range of safe and effective HTLL treatment protocols for patients with different skin types. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Pancreatic fat necrosis in a 10-year-old girl: A case report and review of the literature.

We report here a case of a young girl with pancreatitis and pancreatic fat necrosis (PFN). This condition is rare in the pediatric age group, and its etiopathogenesis is different from disease in adults. Whereas PFN in adults typically results from pancreatitis secondary to pancreatic duct obstruction, alcohol abuse, and pancreatic adenocarcinoma, in children it appears to arise in a setting of systemic disease, often involving a genetic disorder.

Maternal abdominal subcutaneous fat thickness as a simple predictor for gestational diabetes mellitus.

Background To date, only a limited number of studies have evaluated the importance of abdominal subcutaneous fat thickness (ASFT) on gestational diabetes mellitus (GDM) screening. The aim of this study was to investigate the effectiveness of ASFT measurement during routine obstetric ultrasound performed between 24 and 28 weeks of gestation in predicting cases with GDM. Methods This prospective comparative study was conducted on 50 cases with GDM and 50 cases without GDM in the GDM screening program at 24-28 gestational weeks between January 2018 and May 2018. The most accurate ASFT cut-off point values were determined for the prediction of cases with GDM by performing receiver operator characteristic (ROC) curve analysis. Results The ASFT was higher in those with GDM compared to those without GDM (P < 0.05). For an ASFT cut-off point value of 18.1 mm for the prediction of cases with GDM, the sensitivity, specificity, negative and positive predictive values were 72.0%, 60.0%, 64.2% and 68.1%, respectively. The risk of GDM increased 3.86-fold in those with ASFT level >18.1 mm (P = 0.001). Conclusion The ASFT value measured by routine obstetric ultrasound performed at 24-28 weeks of gestation was found to be significantly higher in patients with GDM in comparison to those without GDM. However, further multi-centered and comprehensive prospective studies are required to better demonstrate this relationship.

Sub-Scarpa's Lipectomy in Abdominoplasty: An Analysis of Risks and Rewards in 723 Consecutive Patients.

BACKGROUND: During the course of performing abdominoplasties, a plastic surgeon will encounter a certain body habitus characterized by a thick, tethered, and excessively redundant upper skin flap. Often these patients also demonstrate diffuse and substantial fascial laxity. One approach to this problem involves direct thinning and release of the flap by resection of the sub-Scarpa's fat pad. In theory, this resection should be safe from a flap perfusion standpoint. However, the safety of the sub-Scarpa's resection has not been completely documented. OBJECTIVES: The author sought to assess the safety and efficacy of sub-Scarpa's lipectomy in abdominoplasty. METHODS: A total 723 patients were retrospectively examined and divided into 2 groups: those with (Group B) and those without (Group A) a sub-Scarpa's lipectomy component to the abdominoplasty. Because of differences in the baseline characteristics between the 2 groups, data analysis was performed with a logistic regression model and with propensity score matching. RESULTS: The sub-Scarpa's lipectomy technique allowed for substantial thinning of the flap: the average weight of the resected fat pad was 411 g. Wide undermining allowed for substantial fascial correction, and excellent results were obtainable even in challenging cases. The sub-Scarpa's lipectomy group did not demonstrate an increase in either minor (<5 cm2) or major (>5 cm2) flap necrosis. However, there was a statistically significant increase in fat necrosis and seroma formation in Group B compared with Group A. In both groups, an increasing body mass index was a risk factor for fat necrosis and major flap necrosis. CONCLUSIONS: The implementation of a sub-Scarpa's lipectomy during abdominoplasty is a useful technique to consider for selected abdominoplasty candidates. The risks of minor and major flap loss do not seem to be increased compared to the standard abdominoplasty, but the risks of fat necrosis and seroma formation may be greater.

The TRPC1 Ca2+-permeable channel inhibits exercise-induced protection against high-fat diet-induced obesity and type II diabetes.

The transient receptor potential canonical channel-1 (TRPC1) is a Ca2+-permeable channel found in key metabolic organs and tissues, including the hypothalamus, adipose tissue, and skeletal muscle. Loss of TRPC1 may alter the regulation of cellular energy metabolism resulting in insulin resistance thereby leading to diabetes. Exercise reduces insulin resistance, but it is not known whether TRPC1 is involved in exercise-induced insulin sensitivity. The role of TRPC1 in adiposity and obesity-associated metabolic diseases has not yet been determined. Our results show that TRPC1 functions as a major Ca2+ entry channel in adipocytes. We have also shown that fat mass and fasting glucose concentrations were lower in TRPC1 KO mice that were fed a high-fat (HF) (45% fat) diet and exercised as compared with WT mice fed a HF diet and exercised. Adipocyte numbers were decreased in both subcutaneous and visceral adipose tissue of TRPC1 KO mice fed a HF diet and exercised. Finally, autophagy markers were decreased and apoptosis markers increased in TRPC1 KO mice fed a HF diet and exercised. Overall, these findings suggest that TRPC1 plays an important role in the regulation of adiposity via autophagy and apoptosis and that TRPC1 inhibits the positive effect of exercise on type II diabetes risk under a HF diet-induced obesity environment.

Gastric mucosal devitalization is safe and effective in reducing body weight and visceral adiposity in a porcine model.

BACKGROUND AND AIMS: The early improvement in metabolic profile after sleeve gastrectomy (SG) indicates that the significant benefits of metabolic surgery are gastric in origin. We have previously demonstrated that devitalization of the gastric mucosa (without a reduction in gastric volume) in metabolically disturbed obese rats results in an improvement of obesity and its associated comorbidities. The aims of this study were to assess the technical feasibility, efficacy, and safety of gastric mucosal devitalization (GMD) in a large animal (porcine) model. METHODS: A 3-arm (GMD versus SG versus sham [SH]) prospective randomized controlled trial with an 8-week follow-up period was performed. The primary endpoint was relative weight loss. Secondary endpoints were absolute body weight, abdominal visceral adiposity, abdominal subcutaneous adiposity, organ lipid content, and serum ghrelin level. RESULTS: GMD resulted in a significant relative weight loss of 36% over SH at 8 weeks (P < .05). There was no significant difference in relative weight loss between GMD and SG at 4 weeks; however, SG resulted in a 29% superior relative weight loss at 8 weeks (P < .05). With regard to visceral adiposity, there was a significant benefit of GMD over SH at 8 weeks. Despite differences in relative weight loss, there was no significant difference in visceral adiposity between SG and GMD at 8 weeks. Significant improvements in GMD over SH were noted with regard to skeletal and heart muscle lipid content. GMD pigs at 8 weeks demonstrated regeneration of the gastric mucosa without ulceration or significant scarring. Despite mucosal regeneration, the abundance of serum ghrelin was significantly lower in the GMD cohort compared with the SG and SH cohorts. CONCLUSIONS: GMD was technically feasible and resulted in relative weight loss and an improvement in visceral adiposity. The benefits noted were out of proportion to what would be expected with weight loss alone.

Human Macrophages Preferentially Infiltrate the Superficial Adipose Tissue.

Human abdominal subcutaneous adipose tissue consists of two individual layers—the superficial adipose tissue (SAT) and deep adipose tissue (DAT)—separated by the Scarpa’s fascia. The present study focuses on the analysis of morphological and immunological differences of primary adipocytes, adipose-derived stem cells (ASC), and tissue-infiltrating immune cells found in SAT and DAT. Adipocytes and stromal vascular fraction (SVF) cells were isolated from human SAT and DAT specimens and phenotypically characterized by in vitro assays. Ex vivo analysis of infiltrating immune cells was performed by flow cytometry. Primary adipocytes from SAT are larger in size but did not significantly differ in cytokine levels of LEPTIN, ADIPOQ, RBP4, CHEMERIN, DEFB1, VISFATIN, MCP1, or MSCF. ASC isolated from SAT proliferated faster and exhibited a higher differentiation potential than those isolated from DAT. Flow cytometry analysis indicated no specific differences in the relative numbers of ASC, epithelial progenitor cells (EPC), or CD3⁺ T-cells, but showed higher numbers of tissue-infiltrating macrophages in SAT compared to DAT. Our findings suggest that ASC isolated from SAT have a higher regenerative potential than DAT-ASC. Moreover, spatial proximity to skin microbiota might promote macrophage infiltration in SAT.

Factors regulating subcutaneous adipose tissue storage, fibrosis, and inflammation may underlie low fatty acid mobilization in insulin-sensitive obese adults.

Although the rate of fatty acid release from adipose tissue into the systemic circulation is very high in most obese adults, some obese adults maintain relatively low rates of fatty acid release, which helps protect them against the development of systemic insulin resistance. The primary aim of this study was to identify factors in adipose tissue that may underlie low vs. high rates of fatty acid mobilization in a relatively homogeneous cohort of obese adults. We measured systemic fatty acid rate of appearance (FA Ra) via 13C-palmitate isotope dilution, and we obtained subcutaneous abdominal adipose tissue samples from 30 obese adults (BMI: 38 ± 1 kg/m2, age: 30 ± 2 yr) after an overnight fast. We then measured insulin sensitivity using a hyperinsulinemic-euglycemic clamp. Confirming our previous work, insulin sensitivity was inversely proportional to FA Ra (R2 = 0.50; P < 0.001). Immunoblot analysis of subcutaneous adipose tissue samples revealed that, compared with obese adults with high FA Ra, those with low FA Ra had lower markers of lipase activation and higher abundance of glycerol-3-phosphate acyltransferase, which is a primary enzyme for fatty acid esterification. Microarray and pathway analysis provided evidence of lower fibrosis and lower SAPK/JNK pathway activation in obese adults with low FA Ra compared with those with high FA Ra. Our findings suggest that alterations in factors regulating triglyceride storage in adipose tissue, along with lower fibrosis and inflammatory pathway activation, may underlie maintenance of a relatively low FA Ra in obesity, which may help protect against the development of insulin resistance.

Comprehensive functional screening of miRNAs involved in fat cell insulin sensitivity among women.

The key pathological link between obesity and type 2 diabetes is insulin resistance, but the molecular mechanisms are not entirely identified. micro-RNAs (miRNA) are dysregulated in obesity and may contribute to insulin resistance. Our objective was to detect and functionally investigate miRNAs linked to insulin sensitivity in human subcutaneous white adipose tissue (scWAT). Subjects were selected based on the insulin-stimulated lipogenesis response of subcutaneous adipocytes. Global miRNA profiling was performed in abdominal scWAT of 18 obese insulin-resistance (OIR), 21 obese insulin-sensitive (OIS), and 9 lean women. miRNAs demonstrating differential expression between OIR and OIS women were overexpressed in human in vitro-differentiated adipocytes followed by assessment of lipogenesis and identification of miRNA targets by measuring mRNA/protein expression and 3'-untranslated region analysis. Eleven miRNAs displayed differential expression between OIR and OIS states. Overexpression of miR-143-3p and miR-652-3p increased insulin-stimulated lipogenesis in human in vitro differentiated adipocytes and directly or indirectly affected several genes/proteins involved in insulin signaling at transcriptional or posttranscriptional levels. Adipose expression of miR-143-3p and miR-652-3p was positively associated with insulin-stimulated lipogenesis in scWAT independent of body mass index. In conclusion, miR-143-3p and miR-652-3p are linked to scWAT insulin resistance independent of obesity and influence insulin-stimulated lipogenesis by interacting at different steps with insulin-signaling pathways.

Subcutaneous fat loss is greater than visceral fat loss with diet and exercise, weight-loss promoting drugs and bariatric surgery: a critical review and meta-analysis.

Aim of this review is to compare visceral and subcutaneous fat loss with all available strategies (diet and exercise, weight-loss promoting agents and bariatric surgery). Eighty-nine studies, all full papers, were analyzed to evaluate visceral and subcutaneous fat changes, measured through ultrasound, computerized tomography, magnetic resonance imaging and expressed as thickness, weight, area and volume. Studies were included in a meta-analysis (random-effects model). Intervention effect (absolute and percent changes of visceral and subcutaneous fat) was expressed as standardized mean differences, with 95% confidence intervals. Publication bias was formally assessed. The result was that subcutaneous fat was greater than visceral fat when measured as area, volume and weight, not as thickness; decrease of subcutaneous fat was greater than visceral fat when measured as area, volume and weight, not as thickness; percent decrease of visceral fat was always greater than percent decrease of subcutaneous fat, with no differences between different strategies. No intervention preferentially targets visceral fat. Basal visceral fat depots are smaller than basal subcutaneous fat depots. Visceral fat loss is linked to subcutaneous fat loss. With all strategies, percent decrease of visceral fat prevails on subcutaneous fat loss.

Megasessions: Efficacy of Fewer, Longer Treatment Sessions for Fat Reduction in Noninvasive Body Contouring Using a Radiofrequency Based Device.

While the field of noninvasive body contouring is booming, many patients still note a lesser result than they might achieve with a single session of liposuction or dermolipectomy. The duration of a noninvasive fat reduction treatment series can be daunting. Patients have questioned the worth of these procedures when the expected benefit is modest and the time they devote to the project is significant. An eight-patient mini-study was performed to see if two or three "megasessions" could be substituted for eight weekly sessions of bipolar radiofrequency based fat reduction treatments. Patients were randomized into a two session or three session group by drawing straws. The device used was the BodyFX bipolar RF device by InMode. This device employs a suction coupled vacuum that heats a section of skin and soft tissue in the treatment region and delivers a high voltage pulse. Each patient was treated for 2 hours per session, using the Body FX, more superficial Mini FX, and the Deep FX device in an effort to treat on a multilevel basis. Preoperative 2D and 3D Vectra photos were taken, and were repeated at 1 month and 3 months post-treatment. Volumetric analysis and patient assessment showed similar results with a two or three treatment "megasession" protocol when compared with the traditional protocol of eight weekly sessions. While the cohort number was not statistically significant, the photographs and measurements are compelling enough to warrant further investigation into this treatment protocol.

J Drugs Dermatol. 2017;16(5):478-480.

Adipokines and Vascular Endothelial Growth Factor in Normal Human Breast Tissue in Vivo - Correlations and Attenuation by Dietary Flaxseed.

Exposure to sex steroids increases the risk of breast cancer but the exact mechanisms are yet to be elucidated. Events in the microenvironment are important for carcinogenesis. Diet containing phytoestrogens can affect the breast microenvironment and alter the risk of breast cancer. It has previously been shown that estrogen regulates extracellular levels of leptin, adiponectin, and VEGF in normal breast tissue in vivo. Whether these proteins correlate in breast tissue in vivo or if diet addition of flaxseed, a major source of phytoestrogens in Western diets, alters adipokine levels in breast tissue are unknown. We used microdialysis to sample proteins of normal human breast tissue and abdominal subcutaneous fat in situ in 34 pre-and postmenopausal women. In vitro, co-culture of breast cancer cells and primary human adipocytes was used. In vivo, in normal breast tissue, a significant positive correlation between VEGF and leptin was detected. No correlations were found in fat tissue. Co-culture of adipocytes and breast cancer cells per se increased the secretion of VEGF and leptin and enhanced the effects of estradiol compared to culture of either cell type alone. In vitro, inhibition of VEGF diminished the release of leptin while inhibition of leptin had no influence on VEGF secretion. The levels of leptin decreased and adiponectin increased after a dietary addition of 25 g of flaxseed/day for one menstrual cycle. We conclude that VEGF and leptin correlate significantly in normal human breast tissue in vivo and that dietary addition of flaxseed affect adipokine levels in the breast.

Maternal abdominal subcutaneous fat thickness as a predictor for adverse pregnancy outcome: a longitudinal cohort study.

OBJECTIVE: To assess maternal abdominal subcutaneous fat thickness (SFT) measured by ultrasound as an independent predictor of adverse pregnancy outcomes. DESIGN: A prospective longitudinal cohort study performed on pregnancies delivered between 2012 and 2014. SETTING: Sydney, Australia. POPULATION: About 1510 pregnant women attending routine obstetric ultrasounds. METHODS: Maternal SFT was measured on routine ultrasounds at 11-14 weeks' gestation (SFT1) and 18-22 weeks' gestation (SFT2). SFT measurements were assessed for estimating risks for obesity-related pregnancy outcomes using logistic regression modelling adjusted for maternal age, parity, smoking status and body mass index (BMI). MAIN OUTCOME MEASURES: Hypertensive disease, gestational diabetes, caesarean section, low birthweight, preterm delivery, neonatal respiratory distress, Apgar scores, and admission to a neonatal intensive care unit. RESULTS: SFT1 and SFT2 were measured on 1461 and 1363 women, respectively. Mean thickness (range) were 21.2 mm (6.9-73.9) for SFT1 and 20.3 mm (7.5-68.0) for SFT2. Complete outcome data were available for 1385 pregnancies. In all, 54% of the women were overweight/obese. The SFT measures decreased from early to mid-pregnancy in overweight/obese women. There was moderate correlation between BMI and SFT1 (R(2) = 0.56) and BMI and SFT2 (R(2) = 0.55). In a multivariate model, SFT1 and SFT2 were better predictors for adverse pregnancy outcomes than BMI. CONCLUSION: Maternal SFT is a significant independent predictor of adverse pregnancy outcomes. Incorporation of SFT into future models for adverse pregnancy outcome may prove valuable.