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1.
Sci Rep ; 14(1): 23309, 2024 10 07.
Article in English | MEDLINE | ID: mdl-39375403

ABSTRACT

Breast cancer remains a significant public health issue, often resulting in severe side effects such as neutropenia, highlighting the need for reliable predictors of clinical outcomes. This study aimed to evaluate the predictive value of body composition measures for mortality, recurrence, and chemotherapy-induced neutropenia in patients with breast cancer following surgery and chemotherapy. We retrospectively analyzed 85 breast cancer patients who underwent surgery and chemotherapy between 2006 and 2016. Body composition was assessed using computed tomography (CT) or positron emission tomography (PET) at diagnosis and three years and five years post-diagnosis. Metrics included skeletal muscle area (SMA), skeletal muscle index (SMI), subcutaneous adipose tissue area (SAT), and visceral adipose tissue area (VAT). Longitudinal analysis revealed a decrease in muscle mass (P < 0.001 for both SMA and SMI) and nonsignificant changes in fat mass (P = 0.449 for SAT and P = 0.798 for VAT). A lower SMI at diagnosis was significantly associated with increased mortality (P = 0.019) and a higher incidence of grade 4 neutropenia (P = 0.008). There was no significant association between SMI at diagnosis and recurrence (P = 0.691). No associations were found between body composition measurements during the follow-up period and the clinical outcomes. Lower skeletal muscle mass at diagnosis is strongly associated with higher mortality and chemotherapy-induced complications in patients with breast cancer, highlighting the potential of readily available imaging techniques as valuable predictors of clinical outcomes.


Subject(s)
Body Composition , Breast Neoplasms , Humans , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Breast Neoplasms/mortality , Female , Middle Aged , Prognosis , Retrospective Studies , Aged , Adult , Muscle, Skeletal/diagnostic imaging , Muscle, Skeletal/pathology , Muscle, Skeletal/drug effects , Tomography, X-Ray Computed , Neutropenia/chemically induced , Intra-Abdominal Fat/diagnostic imaging , Positron-Emission Tomography , Neoplasm Recurrence, Local , Subcutaneous Fat/diagnostic imaging , Subcutaneous Fat/pathology
2.
BMC Genomics ; 25(1): 938, 2024 Oct 07.
Article in English | MEDLINE | ID: mdl-39375631

ABSTRACT

BACKGROUND: Epicardial adipose tissue (EAT) surrounds the heart and is hypothesised to play a role in the development of heart failure (HF). In this study, we first investigated the differences in gene expression between epicardial adipose tissue (EAT) and subcutaneous adipose tissue (SAT) in patients undergoing elective coronary artery bypass graft (CABG) surgery (n = 21; 95% male). Secondly, we examined the association between EAT and SAT in patients at risk for HF stage A (n = 12) and in pre-HF patients, who show signs but not symptoms of HF, stage B (n = 9). RESULTS: The study confirmed a distinct separation between EAT and SAT. In EAT 17 clusters of genes were present, of which several novel gene modules are associated with characteristics of HF. Notably, seven gene modules showed significant correlation to measures of HF, such as end diastolic left ventricular posterior wall thickness, e'mean, deceleration time and BMI. One module was particularly distinct in EAT when compared to SAT, featuring key genes such as FLT4, SEMA3A, and PTX3, which are implicated in angiogenesis, inflammation regulation, and tissue repair, suggesting a unique role in EAT linked to left ventricular dysfunction. Genetic expression was compared in EAT across all pre-HF and normal phenotypes, revealing small genetic changes in the form of 18 differentially expressed genes in ACC/AHA Stage A vs. Stage B. CONCLUSIONS: The roles of subcutaneous and epicardial fat are clearly different. We highlight the gene expression difference in search of potential modifiers of HF progress. The true implications of our findings should be corroborated in other studies since HF ACC/AHA stage B patients are common and carry a considerable risk for progression to symptomatic HF.


Subject(s)
Coronary Artery Bypass , Heart Failure , Pericardium , Subcutaneous Fat , Humans , Heart Failure/genetics , Heart Failure/metabolism , Pericardium/metabolism , Pericardium/pathology , Male , Female , Subcutaneous Fat/metabolism , Aged , Middle Aged , Adipose Tissue/metabolism , Gene Expression Profiling , Epicardial Adipose Tissue
3.
BMC Genomics ; 25(1): 850, 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39261767

ABSTRACT

BACKGROUND: Adipose tissue affects not only the meat quality of domestic animals, but also human health. Adipocyte differentiation is regulated by a series of regulatory genes and cyclins. Four and half-LIM protein (FHL2) is positively correlated with the hypertrophy of adipocytes and can cause symptoms such as obesity and diabetes. RESULT: In the transcriptome sequencing analysis of intramuscular adipocytes after three days of differentiation, the differentially expressed gene FHL2 was found. To further explore the biological significance of the differentially expressed gene FHL2, which was downregulated in the mature adipocytes. We revealed the function of FHL2 in adipogenesis through the acquisition and loss of function of FHL2. The results showed that the overexpression of FHL2 significantly increased the expression of adipogenic genes (PPARγ, C/EBPß) and the differentiation of intramuscular and subcutaneous adipocytes. However, silencing FHL2 significantly inhibited adipocyte differentiation. The overexpression of FHL2 increased the number of adipocytes stained with crystal violet and increased the mRNA expression of proliferation marker genes such as CCNE, PCNA, CCND and CDK2. In addition, it significantly increased the rate of EdU positive cells. In terms of apoptosis, overexpression of FHL2 significantly inhibited the expression of P53 and BAX in both intramuscular and subcutaneous adipocytes, which are involved in cell apoptosis. However, overexpression of FHL2 promoted the expression of BCL, but was rescued by the silencing of FHL2. CONCLUSIONS: In summary, FHL2 may be a positive regulator of intramuscular and subcutaneous adipocyte differentiation and proliferation, and acts as a negative regulator of intramuscular and subcutaneous adipocyte apoptosis. These findings provide a theoretical basis for the subsequent elucidation of FHL2 in adipocytes.


Subject(s)
Adipocytes , Adipogenesis , Goats , LIM-Homeodomain Proteins , Muscle Proteins , Animals , Goats/genetics , Adipocytes/metabolism , Adipocytes/cytology , Adipogenesis/genetics , LIM-Homeodomain Proteins/genetics , LIM-Homeodomain Proteins/metabolism , Muscle Proteins/genetics , Muscle Proteins/metabolism , Apoptosis/genetics , Cell Differentiation/genetics , Cell Proliferation , Transcription Factors/genetics , Transcription Factors/metabolism , Subcutaneous Fat/metabolism , Subcutaneous Fat/cytology , Gene Expression Profiling
4.
Sci Rep ; 14(1): 21425, 2024 09 13.
Article in English | MEDLINE | ID: mdl-39271809

ABSTRACT

Oxidative stress in adipose tissue may alter the secretion pattern of adipocytokines and potentially promote atherosclerosis. However, the therapeutic role of hydrogen in adipose tissue under oxidative stress remains unclear. In this study, subcutaneous adipose tissue (SCAT) was collected from the mid-thoracic wounds of 12 patients who underwent open-heart surgery with a mid-thoracic incision. The adipose tissue was then immersed in a culture medium dissolved with hydrogen, which was generated using a hydrogen-generating device. The weight of the adipose tissue was measured before and after hydrogenation, and the tissue was immunostained for nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and superoxide dismutase (SOD), which are markers of oxidative stress. The immunostaining results showed that HO-1 and Nrf2 expression levels were significantly decreased in the hydrogenated group, whereas SOD expression levels increased, but did not attain statistical significance. Image analysis of adipose tissue revealed that a reduction in adipocyte size. Furthermore, hydrogenated adipose tissue showed a trend toward increased gene expression levels of adiponectin and decreased gene expression levels of chemerin, an adipocytokine involved in adipogenesis. These results demonstrated the therapeutic potential of hydrogen gas for oxidative stress in adipose tissue and for reducing adipocyte size.


Subject(s)
Adipose Tissue , Hydrogen , Oxidative Stress , Oxidative Stress/drug effects , Humans , Hydrogen/pharmacology , Hydrogen/metabolism , Male , Female , Adipose Tissue/metabolism , Adipose Tissue/drug effects , Middle Aged , Superoxide Dismutase/metabolism , Heme Oxygenase-1/metabolism , Heme Oxygenase-1/genetics , Aged , Adiponectin/metabolism , Adiponectin/genetics , Adipocytes/metabolism , Adipocytes/drug effects , Subcutaneous Fat/metabolism , Subcutaneous Fat/drug effects , NF-E2-Related Factor 2
5.
J Therm Biol ; 124: 103925, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39241530

ABSTRACT

Intramuscular temperature kinetics can provide insightful information for exercise and environmental physiology research. However, currently, there are no consistent method descriptions or guidelines for muscle temperature assessment in the literature. Studies have reported a great variation in muscle temperature assessment, from 1.5 cm under the skin to 4 cm under the muscle fascia. Moreover, a large variation in body composition components among participants exacerbates this issue, changing the depth and the muscle to be tested. For instance, in young adults (25 ± 5 yrs), the thigh subcutaneous fat thickness can vary from 0.11 to 1.69 cm, and vastus lateralis thickness from 1.62 to 3.38 cm; in older adults (68.5 ± 3 yrs), subcutaneous fat thickness plus gastrocnemius medialis thickness can vary from 1.03 to 3.22 cm. This variation results in inconsistent resting muscle temperature profiles and muscle temperature kinetics during and after an exercise or environmental thermal stress interventions (hot or cold). Hence, one fixed size does not fit all. Standardization and consistency in muscle temperature assessment procedures across studies are required to allow a better understanding and translation of the influence of a given stressor (exercise or thermal) on muscle temperature kinetics. This methodological manuscript i) summarizes the differences in muscle temperature assessment procedures and techniques used across different studies, ii) discusses current concerns related to variations in intramuscular needle depth, and subcutaneous fat and muscle thickness when assessing muscle temperature, and iii) suggests a systematic and more robust approach, based on individual body composition characteristics, to be considered when assessing intramuscular temperature.


Subject(s)
Muscle, Skeletal , Humans , Muscle, Skeletal/physiology , Body Temperature , Exercise/physiology , Subcutaneous Fat/physiology , Body Composition
6.
Anim Biotechnol ; 35(1): 2400212, 2024 Nov.
Article in English | MEDLINE | ID: mdl-39287159

ABSTRACT

Previous studies have shown that subcutaneous adipose tissue is an important energy supply organ for chicks before and after birth, except yolk. So far, the significance of large deposits of subcutaneous adipose tissue in chicks is unclear. Therefore, this study takes the information interaction between adipocytes and macrophages as the starting point to explore whether adipocytes and macrophages could participate in adipose tissue fibrosis, angiogenesis, adaptive thermogenesis and other related functions in a specific metabolic environment. Under cold stress, the expression levels of genes related to lipidolysis, lipid transport and fatty acid oxidation in adipose tissue of chicks were significantly increased, but the expression levels of genes related to mitochondrial uncoupling were not significantly changed. Through Masson staining of adipose tissue of chicks under cold stress, it was found that the level of vascularization in adipose tissue of chicks was significantly increased. We found that the interaction between adipocyte and macrophage could participate in the angiogenesis related process of adipocytes in chicks through the HIF1A-VEGFA pathway. The analysis of lipid metabolism in subcutaneous adipose tissue of chicks from the perspective of cell heterogeneity will expand the understanding of lipid metabolism in chicks and provide a theoretical basis for chick rearing.


Subject(s)
Adipocytes , Chickens , Lipid Metabolism , Macrophages , Neovascularization, Physiologic , Subcutaneous Fat , Animals , Macrophages/metabolism , Macrophages/physiology , Adipocytes/physiology , Adipocytes/metabolism , Subcutaneous Fat/blood supply , Subcutaneous Fat/metabolism , Neovascularization, Physiologic/physiology , Cold-Shock Response/physiology , Cold Temperature , Male , Angiogenesis
7.
Sci Rep ; 14(1): 20836, 2024 09 06.
Article in English | MEDLINE | ID: mdl-39242580

ABSTRACT

Recent reports have shown that pre-treatment low muscle mass may lead to poorer outcomes for cancer patients. We explored the correlation between Visceral Adipose Tissue (VAT), Subcutaneous Adipose Tissue (SAT), and Muscle Mass (MM) as measured by CT scans, and overall survival (OS) following diagnosis of colorectal cancer (CRC). We conducted a retrospective review of medical records and CT scans of patients diagnosed with CRC between 2007 and 2018. Demographics, pathology, and clinical parameters were collected. Using Image-J software, we measured VAT, SAT, and MM. Survival rates were analyzed using Kaplan-Meier curves, and prognostic factors were assessed using multivariate Cox regression. Analysis included 408 patients with a mean age of 56.9 years and a median follow-up of 93.3 months. Colon and rectum/rectosigmoid colon cancers were equally distributed. The 5-year OS rate was 67.8%. There was no significant difference in OS rates based on SAT or VAT. However, higher MM was associated with a improved 5-year OS rate. Factors such as age, stage, grade, and surgery were also associated to OS rates. These findings suggest that higher muscle mass may lead to better outcomes for CRC patients, highlighting the potential impact of exercise and nutritional interventions on patient outcomes.


Subject(s)
Colorectal Neoplasms , Humans , Male , Middle Aged , Female , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Retrospective Studies , Aged , Prognosis , Intra-Abdominal Fat/pathology , Adult , Tertiary Care Centers , Tomography, X-Ray Computed , Survival Rate , Subcutaneous Fat/pathology , Subcutaneous Fat/diagnostic imaging , Kaplan-Meier Estimate , Muscle, Skeletal/pathology , Muscle, Skeletal/diagnostic imaging
8.
Obes Res Clin Pract ; 18(4): 263-268, 2024.
Article in English | MEDLINE | ID: mdl-39277538

ABSTRACT

AIMS: Visceral fat predicts the development of metabolic syndrome (MetS), but it is not known whether the visceral to subcutaneous fat area ratio (VSR) measured using imaging predicts MetS risk as well or better. Thus, we aimed to examine if VSR predicted future risk of MetS over 10-years. METHODS: We followed 329 participants in the longitudinal Japanese American Community Diabetes Study without MetS at baseline for its development over 10 years. Intra-abdominal (VFA) and subcutaneous abdominal (SFA) fat areas were measured at baseline and 10-years and used to calculate VSR. Logistic regression was used to estimate the odds of incident MetS by baseline and 10-year change in VSR and other adipose depots with and without adjustment for baseline MetS features. Areas under ROC curves were calculated in predicting the development of MetS. RESULTS: 99 participants developed MetS over 10-years. Logistic regression models showed a higher odds of incident MetS with greater VSR and 10-year VSR change (OR = 1.67, 95 % CI 1.11-2.51; OR = 1.46, 95 % CI 1.06-2.01, respectively) adjusting for age, sex, and MetS features at baseline. However, VSR alone performed poorly at discriminating (AUROC 0.5807) compared to VFA (AUROC 0.6970, p < 0.001) or a logistic model incorporating VFA and SFA (AUROC 0.7221, p = 0.001). CONCLUSIONS: VSR and VFA predict 10-year MetS risk in Japanese Americans, confirming the importance of relatively greater fat distribution in the visceral depot in the development of MetS. However, VSR is a weaker predictor of MetS development and provides less information compared to VFA alone, and its further use in predicting metabolic abnormalities is not recommended.


Subject(s)
Asian , Intra-Abdominal Fat , Metabolic Syndrome , Subcutaneous Fat , Humans , Metabolic Syndrome/epidemiology , Female , Male , Middle Aged , Subcutaneous Fat/diagnostic imaging , Prospective Studies , Asian/statistics & numerical data , Risk Factors , Aged , Longitudinal Studies , Logistic Models , Adult , Japan/epidemiology
9.
Sci Rep ; 14(1): 20896, 2024 09 08.
Article in English | MEDLINE | ID: mdl-39245685

ABSTRACT

The purpose of this study is to evaluate whether the periprostatic adipose tissue thickness (PPATT) is an independent prognostic factor for prostate cancer patients after laparoscopic radical prostatectomy (LRP). This retrospective cohort study included consecutive prostate cancer patients who underwent LRP treatment at Wuhan Union Hospital from June 2, 2016, to September 7, 2023. PPATT was defined as the thickness of periprostatic fat and was obtained by measuring the shortest vertical distance from the pubic symphysis to the prostate on the midsagittal T2-weighted MR images. Subcutaneous adipose tissue thickness (SATT) was obtained by measuring the shortest vertical distance from the pubic symphysis to the skin at the same slice with PPATT. The primary outcome of the study was biochemical recurrence (BCR), and the secondary outcome was overall survival (OS). Multivariable Cox regression analysis was used to identify independent prognostic factors for prostate cancer survival and prognosis. Based on the optimal cutoff value, 162 patients were divided into a low PPATT/SATT group (n = 82) and a high PPATT/SATT group (n = 80). During the entire follow-up period (median 23.5 months), 26 patients in the high PPATT/SATT group experienced BCR (32.5%), compared to 18 in the low PPATT/SATT group (22.0%). Kaplan-Meier curve analysis indicated that the interval to BCR was significantly shorter in the high PPATT/SATT group (P = 0.037). Multivariable Cox regression analysis revealed that an increase in the PPATT/SATT ratio was associated with BCR (hazard ratio: 1.90, 95% CI, 1.03-3.51; P = 0.040). The PPATT/SATT ratio is a significant independent risk factor for BCR after LRP for prostate cancer patients.


Subject(s)
Magnetic Resonance Imaging , Prostate , Prostatectomy , Prostatic Neoplasms , Subcutaneous Fat , Humans , Male , Prostatic Neoplasms/surgery , Prostatic Neoplasms/pathology , Prostatic Neoplasms/diagnostic imaging , Middle Aged , Aged , Subcutaneous Fat/diagnostic imaging , Subcutaneous Fat/pathology , Magnetic Resonance Imaging/methods , Risk Factors , Retrospective Studies , Prostate/pathology , Prostate/surgery , Prostate/diagnostic imaging , Prognosis , Neoplasm Recurrence, Local/diagnostic imaging , Neoplasm Recurrence, Local/pathology
10.
Int J Mol Sci ; 25(16)2024 Aug 19.
Article in English | MEDLINE | ID: mdl-39201693

ABSTRACT

In adipose tissue, reduced expression of the glycerol channel aquaporin 7 (AQP7) has been associated with increased accumulation of triglyceride. The present study determines the relative protein abundances of lipolytic enzymes, AQP7, and cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) in paired mesenteric and omental visceral adipose tissue (VAT) and abdominal and femoral subcutaneous adipose tissue (SAT) in women with either normal weight or upper-body obesity. No differences in the expression of hormone-sensitive lipase (HSL) or AQP7 were found between the two groups in the four depots. The expression of adipocyte triglyceride lipase (ATGL) and HSL were higher in omental VAT and femoral SAT than in mesenteric VAT in both groups of women. Similarly, AQP7 expression was higher in omental VAT than in mesenteric VAT. The expression of PEPCK-C was lower in omental VAT than in femoral SAT. No correlation between the expression of AQP7 and the mean adipocyte size was observed; however, the expression of PEPCK-C positively correlated with the mean adipocyte size. In conclusion, a depot-specific protein expression pattern was found for ATGL, HSL, AQP7, and PEPCK-C. The expression pattern supports that the regulation of AQP7 protein expression is at least in part linked to the lipolytic rate. Furthermore, the results support that the synthesis of glycerol-3-phosphate via glyceroneogenesis contributes to regulating triglyceride accumulation in white adipose tissue in women.


Subject(s)
Aquaporins , Glycerol , Intra-Abdominal Fat , Obesity , Subcutaneous Fat , Humans , Female , Subcutaneous Fat/metabolism , Aquaporins/metabolism , Aquaporins/genetics , Glycerol/metabolism , Intra-Abdominal Fat/metabolism , Obesity/metabolism , Obesity/pathology , Adult , Middle Aged , Lipolysis , Sterol Esterase/metabolism , Sterol Esterase/genetics , Lipase/metabolism , Lipase/genetics , Phosphoenolpyruvate Carboxykinase (ATP)/metabolism , Phosphoenolpyruvate Carboxykinase (ATP)/genetics , Adipocytes/metabolism , Triglycerides/metabolism , Acyltransferases
11.
Ann Plast Surg ; 93(2S Suppl 1): S64-S68, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39101851

ABSTRACT

BACKGROUND: Temporal concavities result from reduced subcutaneous fat and bone structure variations, impacting facial aesthetics. Filling treatments, including autologous fat grafts, synthetic fillers, and biological materials, are used for enhancement. Autologous fat grafting is promising but limited by unpredictable fat absorption and nonstandardized procedures. This study aims to assess the clinical effectiveness of mechanical micronized fat in combination with autologous granular fat grafting for lipofilling in the correction of temporal deformities. METHODS: Patients (n = 37, mean age = 37.48) with temporal concavity caused by aging and Inherently inadequate capacity were enrolled and divided into control group (n = 10) and study group (n = 9) according to different fat grafts. Control group received pure autologous granular fat, with an average volume of approximately 19.30 mL. In contrast, the study group used mechanical micronized fat along with autologous granular fat co-injection through an 18G needle with an average injection volume of about 18.89 mL. All autologous fat collected from patients' abdominal and thighs. Information, including postoperative clinical efficacy scored by various plastic surgeons for the comparison of preoperative and postoperative photos of patients, patient satisfaction, and complications between the two groups, was documented. Additionally, changes in patients' quality of life were evaluated using the FACE-Q scale. RESULTS: Six months after surgery, the efficacy of temporal filling in the study group (6.69 ± 0.64) was higher than the control group (6.37 ± 0.67) (P = 0.0048). The patient satisfaction was more prominent in the study group (6.28 ± 0.87) than in the control group (5.80 ± 0.71) (P = 0.0449). Differences between above two observation indicators were statistically significant (P < 0.05). The FACE-Q scale items, which assess psychological health, social functioning, and early life impact, showed higher scores in the study group both before the surgery (psychological health: 59.22 ± 3.53, social functioning: 64.75 ± 3.15) and 6 months after the surgery (psychological health: 69.44 ± 4.50, social functioning: 75.33 ± 3.81, early life impact: 74.21 ± 0.70) (P > 0.05). Notably, only one micronodule formation was detected among all patients. CONCLUSION: Mechanical micronized fat combined with autologous granular fat improve the clinical effect of treating concavity in temporal region, which is worthy of further promotion and application.


Subject(s)
Adipose Tissue , Humans , Female , Adult , Male , Adipose Tissue/transplantation , Middle Aged , Treatment Outcome , Transplantation, Autologous , Patient Satisfaction , Esthetics , Quality of Life , Subcutaneous Fat/transplantation
12.
Obesity (Silver Spring) ; 32(10): 1870-1884, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39210585

ABSTRACT

OBJECTIVE: The objective was to study metabolic characteristics and transcriptome of renal sinus adipose tissue (RSAT) located around renal arteries and veins. METHODS: Adipose tissue biopsies from RSAT, omental (OAT), and subcutaneous (SAT) depots were obtained from healthy kidney donors (20 female, 20 male). Adipocyte glucose uptake rate and cell size were measured, and gene expression analyses using transcriptomics were performed. RESULTS: RSAT adipocytes were significantly smaller, with a higher basal glucose uptake rate, than adipocytes from SAT and OAT. Transcriptomic analyses revealed 29 differentially expressed genes between RSAT and OAT (RSAT: 23 lower, 6 higher) and 1214 differentially expressed genes between RSAT and SAT (RSAT: 859 lower, 355 higher). RSAT demonstrated molecular resemblance to OAT, both exhibiting lower metabolic gene expression and higher expression of immune-related pathways, including IL-17, TNFα, and NF-κB signaling than SAT. Weighted gene coexpression network analysis associated RSAT with immune response and nucleic acid transport processes. Despite its location near the renal hilum, RSAT closely resembled OAT and there was a lack of expression in the classical brown adipose tissue genes. Gene enrichment analyses suggest an inflammatory environment in RSAT compared with SAT and, to some extent, OAT. CONCLUSIONS: The findings suggest specific RSAT functions that could impact renal function and, possibly, the development of renal and cardiometabolic disorders.


Subject(s)
Omentum , Subcutaneous Fat , Transcriptome , Humans , Female , Male , Omentum/metabolism , Subcutaneous Fat/metabolism , Adult , Middle Aged , Adipocytes/metabolism , Adipose Tissue/metabolism , Kidney/metabolism , Gene Expression Profiling , Glucose/metabolism
13.
J Cosmet Dermatol ; 23(10): 3133-3143, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39166716

ABSTRACT

BACKGROUND: Obesity and localized fat accumulation continue to drive the demand for minimally invasive body contouring technologies including injectable compounds for local fat reduction. siRNA offers a potential for an injectable to specifically target and silence genes involved in adipogenesis with minimal inflammatory side effects. AIMS: This study evaluates the efficacy of STP705, an injectable containing siRNA encapsulated within histidine-lysine polypeptide (HKP) nanoparticles targeting transforming growth factor ß1 (TGF-ß1) and cyclooxygenase-2 (COX-2), crucial mediators in adipocyte differentiation and fat retention, using in vitro, porcine, and murine models. METHODS: In vitro experiments on mouse preadipocytes and in vivo trials using Diet Induced Obese (DIO) mice and Yucatan minipigs were conducted to assess the gene silencing efficiency, tissue localization, pharmacodynamics, and safety profile of STP705. RESULTS: STP705 effectively reduced the expression of TGF-ß1 and COX-2, with a notable decrease in adipocyte volume and lipid content without adverse systemic effects. In DIO mice, the HKP-siRNA complex demonstrated precise localization to injected adipose tissue, maintaining significant gene silencing, and detectable levels of siRNA for up to 14 days post-administration. Similar results in minipigs showed a significant reduction in subcutaneous adipose tissue thickness. CONCLUSION: The results of these studies support the use of targeted siRNA therapy specifically targeting TGF-ß1 and COX-2, for localized fat reduction, offering a potential minimally invasive alternative to current fat reduction methods.


Subject(s)
Adipocytes , Cyclooxygenase 2 , Nanoparticles , Peptides , RNA, Small Interfering , Swine, Miniature , Transforming Growth Factor beta1 , Animals , RNA, Small Interfering/administration & dosage , RNA, Small Interfering/pharmacology , Transforming Growth Factor beta1/metabolism , Transforming Growth Factor beta1/genetics , Nanoparticles/administration & dosage , Swine , Cyclooxygenase 2/metabolism , Cyclooxygenase 2/genetics , Mice , Peptides/administration & dosage , Adipocytes/drug effects , Obesity/metabolism , Obesity/therapy , Adipogenesis/drug effects , Disease Models, Animal , Gene Silencing/drug effects , Subcutaneous Fat/drug effects , Subcutaneous Fat/metabolism
14.
Nutrients ; 16(16)2024 Aug 06.
Article in English | MEDLINE | ID: mdl-39203715

ABSTRACT

The present study aimed to (a) assess normal-weight obesity (NWO) and general obesity prevalence among women of different ages residing in urban areas, (b) evaluate subcutaneous fat thickness (SFT) in women with NWO, (c) establish SFT cutoff points for distinguishing NWO, and (d) explore eating habits linked to NWO. This cross-sectional study with 184 women aged 18-65 with NWO, normal weight without obesity (NWNO), overweight and general obesity included evaluation of body composition, SFT assessment using 2.5 MHz A-mode ultrasound (ISAK protocol, 7 sites) and lifestyle inquiries. The curvilinear relationship between body fat and BMI rendered BMI an unreliable indicator of adiposity in women with normal weight (BMI < 25 kg/m2). Almost 30% of women with a high body fat percentage (BFP ≥ 30%) were misclassified when BMI was used to measure adiposity. The overall obesity prevalence defined by BFP was almost four times higher than that defined by BMI (56.0 vs. 18.0%, p = 1 × 10-4). Women with NWO, overweight and general obesity shared a similar SFT profile and eating habits, setting them apart from those with NWNO. The mean SFT was the most reliable NWO predictor, with a threshold set at 12 mm equal to the 66th percentile. Mean SFT accurately classified 85% of women with NWO. While age did not significantly affect subcutaneous fat accumulation, total fat levels increased with age (R2 = 0.07 and R2 = 0.19, padj = 0.1 and padj = 9 × 10-4). Higher NWO prevalence in middle-aged women was linked to age-related increase in fat mass and decrease in fat-free mass. Engaging in regular physical activity and reducing snack consumption effectively countered age-related changes in body composition (padj < 0.05). Women under 45 years who consumed sweet bakery items, fast food, and snacks more frequently showed higher BFP and NWO status (padj < 0.05). Prevention strategies should focus on monitoring body composition and promoting healthy behaviors, particularly among young women transitioning into adulthood and women over 45 years.


Subject(s)
Body Mass Index , Obesity , Humans , Female , Adult , Middle Aged , Prevalence , Obesity/epidemiology , Cross-Sectional Studies , Young Adult , Adolescent , Aged , Adiposity , Feeding Behavior , Body Composition , Subcutaneous Fat/diagnostic imaging , Body Weight , Life Style
15.
Nat Commun ; 15(1): 7013, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-39147741

ABSTRACT

Molecular effects of lifestyle interventions are typically studied in a single tissue. Here, we perform a secondary analysis on the sex-specific effects of the Growing Old TOgether trial (GOTO, trial registration number GOT NL3301 ( https://onderzoekmetmensen.nl/nl/trial/27183 ), NL-OMON27183 , primary outcomes have been previously reported in ref. 1), a moderate 13-week combined lifestyle intervention on the transcriptomes of postprandial blood, subcutaneous adipose tissue (SAT) and muscle tissue in healthy older adults, the overlap in effect between tissues and their relation to whole-body parameters of metabolic health. The GOTO intervention has virtually no effect on the postprandial blood transcriptome, while the SAT and muscle transcriptomes respond significantly. In SAT, pathways involved in HDL remodeling, O2/CO2 exchange and signaling are overrepresented, while in muscle, collagen and extracellular matrix pathways are significantly overexpressed. Additionally, we find that the effects of the SAT transcriptome closest associates with gains in metabolic health. Lastly, in males, we identify a shared variation between the transcriptomes of the three tissues. We conclude that the GOTO intervention has a significant effect on metabolic and muscle fibre pathways in the SAT and muscle transcriptome, respectively. Aligning the response in the three tissues revealed a blood transcriptome component which may act as an integrated health marker for metabolic intervention effects across tissues.


Subject(s)
Life Style , Subcutaneous Fat , Transcriptome , Humans , Male , Female , Aged , Subcutaneous Fat/metabolism , Muscle, Skeletal/metabolism , Postprandial Period , Middle Aged
16.
Sci Rep ; 14(1): 19063, 2024 08 17.
Article in English | MEDLINE | ID: mdl-39154084

ABSTRACT

Abdominal adhesions manifests following abdominal infections triggered by intestinal fistulas. The severity of such adhesions depends on the extent of fiber deposition and peritoneal fibrinolysis following peritoneal injury, which may be influenced by sustained inflammation within the abdominal cavity. In this regard, the visceral-to-subcutaneous fat area (VFA/SFA) ratio has been implicated as a potential marker of inflammation. This study aimed to explore the relationship between VFA/SFA and abdominal adhesions. This multicenter study was conducted across four tertiary institutions and involved patients who had undergone definitive surgery (DS) for intestinal fistula from January 2009 and October 2023. The presence of abdominal adhesions was determined intraoperatively. VFA/SFA was investigated as a potential risk factor for severe adhesions. The study comprised 414 patients with a median age of 50 [interquartile range (IQR) 35-66] years and a median body mass index of 20.0 (IQR 19.2-22.4) kg/m2, including 231 males with a median VFA/SFA of 1.0 (IQR 0.7-1.2) and 183 females a median VFA/SFA of 0.8 (0.6-1.1). VFA/SFA was associated with severe abdominal adhesions in males [odds ratio (OR) = 3.34, 95% CI 1.14-9.80, p = 0.03] and females (OR = 2.99, 95% CI 1.05-8.53, p = 0.04). J-shaped association between VFA/SFA ratio and severe adhesions was revealed in both sex. The increasing trend can be revealed when OR more than 0.8, and 0.6 in males and females respectively. Preoperative VFA/SFA demonstrates predictive value for statues of severe abdominal adhesions in DS for anastomotic fistula after small intestine resection.


Subject(s)
Intestinal Fistula , Intestine, Small , Intra-Abdominal Fat , Subcutaneous Fat , Humans , Male , Female , Tissue Adhesions/etiology , Tissue Adhesions/pathology , Middle Aged , Aged , Adult , Intestine, Small/surgery , Intestine, Small/pathology , Subcutaneous Fat/pathology , Intestinal Fistula/etiology , Intestinal Fistula/surgery , Postoperative Complications/etiology , Risk Factors
17.
Nutrients ; 16(15)2024 Aug 03.
Article in English | MEDLINE | ID: mdl-39125437

ABSTRACT

In humans, α-tocopherol (α-TOC) is mainly stored in adipose tissue, where it participates in preventing damages induced by inflammation and reactive oxygen species. Factors, including genetic ones, that explain adipose tissue α-TOC concentration remain poorly understood. This study, therefore, aimed to characterize the interindividual variability of adipose tissue α-TOC concentration in healthy individuals and to identify single nucleotide polymorphisms (SNPs) associated with it. The study used a randomized cross-over design with 42 healthy adult males. α-TOC concentration was measured in fasting plasma and periumbilical adipose tissue samples, both at fast and 8 h after consumption of three standard meals. Partial least squares (PLS) regression was performed to identify SNPs associated with the interindividual variability of adipose tissue α-TOC concentration. Adipose tissue α-TOC concentration was not associated with fasting plasma concentration (Pearson's r = 0.24, 95% CI: [-0.08, 0.51]). There was a high interindividual variability of adipose tissue α-TOC concentration (CV = 61%). A PLS regression model comprising 10 SNPs in five genes (PPARG, ABCA1, BUD13, CD36, and MGLL) explained 60% (adjusted R2) of the variability of this concentration. The interindividual variability of adipose tissue α-TOC concentration in humans is due, at least partly, to SNPs in genes involved in α-TOC and triglyceride metabolism.


Subject(s)
Cross-Over Studies , Polymorphism, Single Nucleotide , Subcutaneous Fat , alpha-Tocopherol , Humans , Male , alpha-Tocopherol/blood , alpha-Tocopherol/metabolism , Adult , Subcutaneous Fat/metabolism , Young Adult , Fasting , ATP Binding Cassette Transporter 1/genetics , ATP Binding Cassette Transporter 1/metabolism , CD36 Antigens/genetics , CD36 Antigens/metabolism , Healthy Volunteers
18.
Cells ; 13(15)2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39120271

ABSTRACT

Adipose tissue is a dynamic regulatory organ that has profound effects on the overall health of patients. Unfortunately, inconsistencies in human adipose tissues are extensive and multifactorial, including large variability in cellular sizes, lipid content, inflammation, extracellular matrix components, mechanics, and cytokines secreted. Given the high human variability, and since much of what is known about adipose tissue is from animal models, we sought to establish correlations and patterns between biological, mechanical, and epidemiological properties of human adipose tissues. To do this, twenty-six independent variables were cataloged for twenty patients, which included patient demographics and factors that drive health, obesity, and fibrosis. A factorial analysis for mixed data (FAMD) was used to analyze patterns in the dataset (with BMI > 25), and a correlation matrix was used to identify interactions between quantitative variables. Vascular endothelial growth factor A (VEGFA) and actin alpha 2, smooth muscle (ACTA2) gene expression were the highest loadings in the first two dimensions of the FAMD. The number of adipocytes was also a key driver of patient-related differences, where a decrease in the density of adipocytes was associated with aging. Aging was also correlated with a decrease in overall lipid percentage of subcutaneous tissue, with lipid deposition being favored extracellularly, an increase in transforming growth factor-ß1 (TGFß1), and an increase in M1 macrophage polarization. An important finding was that self-identified race contributed to variance between patients in this study, where Black patients had significantly lower gene expression levels of TGFß1 and ACTA2. This finding supports the urgent need to account for patient ancestry in biomedical research to develop better therapeutic strategies for all patients. Another important finding was that TGFß induced factor homeobox 1 (TGIF1), an understudied signaling molecule, which is highly correlated with leptin signaling, was correlated with metabolic inflammation. Furthermore, this study draws attention to what we define as "extracellular lipid droplets", which were consistently found in collagen-rich regions of the obese adipose tissues evaluated here. Reduced levels of TGIF1 were correlated with higher numbers of extracellular lipid droplets and an inability to suppress fibrotic changes in adipose tissue. Finally, this study indicated that M1 and M2 macrophage markers were correlated with each other and leptin in patients with a BMI > 25. This finding supports growing evidence that macrophage polarization in obesity involves a complex, interconnecting network system rather than a full switch in activation patterns from M2 to M1 with increasing body mass. Overall, this study reinforces key findings in animal studies and identifies important areas for future research, where human and animal studies are divergent. Understanding key drivers of human patient variability is required to unravel the complex metabolic health of unique patients.


Subject(s)
Subcutaneous Fat , Humans , Subcutaneous Fat/metabolism , Male , Female , Middle Aged , Adult , Adipocytes/metabolism , Obesity/metabolism , Obesity/pathology , Actins/metabolism , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor A/genetics , Aged
19.
Endocrinol Metab (Seoul) ; 39(4): 632-640, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39015029

ABSTRACT

BACKGRUOUND: Osteoporosis and fragility fractures are crucial musculoskeletal complications in long-term survivors of gastric cancer. However, the relationship between changes in body composition after gastrectomy and bone loss has not been investigated. Therefore, this study aimed to explore whether computed tomography (CT)-derived body composition parameters are associated with bone loss after gastrectomy in patients with gastric cancer. METHODS: We retrospectively reviewed medical records and abdomen CT scans of patients who underwent gastrectomy at Yonsei University Severance Hospital between 2009 and 2018. Patients with non-metastatic gastric adenocarcinoma and preoperative and postoperative non-contrast CT scans were analyzed. Section area of skeletal muscle (SMA), visceral fat (VFA), and subcutaneous fat (SFA) were assessed using semi-automatic segmentation software. Changes in trabecular bone attenuation of L1 mid-vertebra level (L1 Hounsfield units [HU]) were measured. RESULTS: Fifty-seven patients (mean age, 65.5±10.6; 70.2% males) were analyzed, and the median duration was 31 months. Fortyseven patients (82.5%) lost weight after gastrectomy. Baseline SMA and VFA did not differ between the bone loss and preserved groups; however, baseline SFA was significantly higher in the bone preserved group than in the bone loss group (P=0.020). In a multivariable linear regression model adjusted for confounding factors, one standard deviation higher VFA at baseline was associated with greater annualized L1 HU loss (%) (P=0.034). However, higher preoperative SFA was associated with protection against bone loss after gastrectomy (P=0.025). CONCLUSION: Higher preoperative SFA exhibited a protective effect against bone loss after gastrectomy in patients with non-metastatic gastric cancer, whereas VFA exhibited a negative effect.


Subject(s)
Gastrectomy , Intra-Abdominal Fat , Osteoporosis , Stomach Neoplasms , Subcutaneous Fat , Tomography, X-Ray Computed , Humans , Gastrectomy/adverse effects , Male , Female , Subcutaneous Fat/diagnostic imaging , Intra-Abdominal Fat/diagnostic imaging , Aged , Retrospective Studies , Stomach Neoplasms/surgery , Middle Aged , Osteoporosis/etiology , Osteoporosis/diagnostic imaging , Body Composition , Bone Density , Adenocarcinoma/surgery
20.
J Anesth ; 38(5): 674-680, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38990343

ABSTRACT

PURPOSE: The causes of epidural catheter migration beneath the skin have not been previously investigated. We hypothesized that greater subcutaneous fat thickness might be associated with increased catheter migration beneath the skin. METHODS: We conducted a retrospective cross-sectional study of patients who had undergone combined general and epidural anesthesia, selecting individuals who received thoracic and abdominal CT scans within the first 5 postoperative days. Needle depth was defined as the distance from the needle tip to the skin surface when the anesthesiologist determined that the needle tip had reached the epidural space. We measured the length of the epidural catheter from the skin surface to the epidural space (catheter length), and subcutaneous fat thickness (fat thickness) using CT imaging. Migration distance was calculated by subtracting needle depth from catheter length. RESULTS: We analyzed 127 patients (72 males), all undergoing epidural catheter insertion in the left lateral decubitus position via a paramedian approach. The median age of the patients was 71 years. Epidural catheters were postoperatively found to substantially curve beneath the skin. Regression analysis revealed no significant influence of fat thickness on catheter length (regression coefficient 0.10, 95% confidence interval [CI]: - 0.17, 0.38). However, it indicated a positive correlation between fat thickness and needle depth (regression coefficient 0.50, 95% CI: 0.30, 0.70), and a negative correlation between fat thickness and migration distance (regression coefficient - 0.40, 95% CI: - 0.65, - 0.14). CONCLUSION: We found a negative correlation between epidural catheter migration beneath the skin and subcutaneous fat thickness. Anesthesiologists should be aware of the possibility of substantial subcutaneous curving of the catheter, especially in patients with scant subcutaneous fat.


Subject(s)
Anesthesia, Epidural , Epidural Space , Foreign-Body Migration , Skin , Subcutaneous Fat , Tomography, X-Ray Computed , Humans , Male , Cross-Sectional Studies , Retrospective Studies , Female , Aged , Subcutaneous Fat/diagnostic imaging , Tomography, X-Ray Computed/methods , Anesthesia, Epidural/methods , Anesthesia, Epidural/adverse effects , Middle Aged , Foreign-Body Migration/diagnostic imaging , Foreign-Body Migration/etiology , Epidural Space/diagnostic imaging , Skin/diagnostic imaging , Catheters , Aged, 80 and over , Postoperative Period , Adult
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