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1.
J Clin Endocrinol Metab ; 107(2): e836-e851, 2022 01 18.
Article in English | MEDLINE | ID: mdl-34448000

ABSTRACT

CONTEXT: MSCA1 (mesenchymal stem cell antigen 1) and CD36 (cluster of differentiation 36) have been described as novel adipocyte progenitor markers in adults with a potential relevance for obesity and adipocyte progenitor function. OBJECTIVE: With the early manifestation of obesity in children and formation of adipose tissue (AT) dysfunction, children provide the opportunity to characterize the function of MSCA1 and CD36 during physiological AT accumulation and with obesity and related disease. METHODS: We investigated MSCA1 and CD36 expression in adipocytes and stroma vascular fraction (SVF) cells from 133 children of the Leipzig AT Childhood cohort with regard to AT accumulation and biology. In a subsample we analyzed how MSCA1 and CD36 expression is related to adipose progenitor capacities in vitro (ie, proliferation, differentiation and mitochondrial function). RESULTS: Both MSCA1 and CD36 are differentially expressed in adipocytes and SVF cells of children. MSCA1 expression is positively correlated to obesity-associated AT dysfunction (ie, adipocyte hypertrophy and serum high-sensitivity C-reactive protein), and high SVF MSCA1 expression is associated with increased mitochondrial respiration in vitro. CD36 expression is not associated with AT dysfunction but SVF CD36 expression is downregulated in children with overweight and obesity and shows a positive association with the differentiation capacity of SVF cells ex vivo and in vitro. CONCLUSION: Both MSCA1 and CD36 are associated with obesity-related alterations in AT of children. In particular, CD36 expression predicts adipogenic potential of SVF cells, indicating a potential role in the regulation of adipocyte hyperplasia and hypertrophy with obesity development in children.


Subject(s)
Adipogenesis , Antigens, Surface/metabolism , Pediatric Obesity/physiopathology , Subcutaneous Fat/physiopathology , Adipocytes/metabolism , Adolescent , Antigens, Surface/analysis , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Infant , Male , Stromal Vascular Fraction/metabolism , Subcutaneous Fat/cytology , Subcutaneous Fat/metabolism
2.
Int J Obes (Lond) ; 45(9): 2083-2094, 2021 09.
Article in English | MEDLINE | ID: mdl-34103691

ABSTRACT

BACKGROUND/OBJECTIVES: The incidence of obesity continues to increase worldwide and while the underlying pathogenesis remains largely unknown, nutrient excess, manifested by "Westernization" of the diet and reduced physical activity have been proposed as key contributing factors. Western-style diets, in addition to higher caloric load, are characterized by excess of advanced glycation end products (AGEs), which have been linked to the pathophysiology of obesity and related cardiometabolic disorders. AGEs can be "trapped" in adipose tissue, even in the absence of diabetes, in part due to higher expression of the receptor for AGEs (RAGE) and/or decreased detoxification by the endogenous glyoxalase (GLO) system, where they may promote insulin resistance. It is unknown whether the expression levels of genes linked to the RAGE axis, including AGER (the gene encoding RAGE), Diaphanous 1 (DIAPH1), the cytoplasmic domain binding partner of RAGE that contributes to RAGE signaling, and GLO1 are differentially regulated by the degree of obesity and/or how these relate to inflammatory and adipocyte markers and their metabolic consequences. SUBJECTS/METHODS: We sought to answer this question by analyzing gene expression patterns of markers of the AGE/RAGE/DIAPH1 signaling axis in abdominal subcutaneous (SAT) and omental (OAT) adipose tissue from obese and morbidly obese subjects. RESULTS: In SAT, but not OAT, expression of AGER was significantly correlated with that of DIAPH1 (n = 16; [Formula: see text], [0.260, 1.177]; q = 0.008) and GLO1 (n = 16; [Formula: see text], [0.364, 1.182]; q = 0.004). Furthermore, in SAT, but not OAT, regression analyses revealed that the expression pattern of genes in the AGE/RAGE/DIAPH1 axis is strongly and positively associated with that of inflammatory and adipogenic markers. Remarkably, particularly in SAT, not OAT, the expression of AGER positively and significantly correlated with HOMA-IR (n = 14; [Formula: see text], [0.338, 1.249]; q = 0.018). CONCLUSIONS: These observations suggest associations of the AGE/RAGE/DIAPH1 axis in the immunometabolic pathophysiology of obesity and insulin resistance, driven, at least in part, through expression and activity of this axis in SAT.


Subject(s)
Insulin Resistance/physiology , Omentum/physiopathology , Subcutaneous Fat/physiopathology , Adipose Tissue/physiopathology , Adult , Antigens, Neoplasm/analysis , Antigens, Neoplasm/blood , Female , Formins/analysis , Formins/blood , Humans , Male , Middle Aged , Mitogen-Activated Protein Kinases/analysis , Mitogen-Activated Protein Kinases/blood , Obesity/blood , Obesity/physiopathology , Omentum/abnormalities , Receptor for Advanced Glycation End Products/analysis , Receptor for Advanced Glycation End Products/blood , Subcutaneous Fat/abnormalities
3.
Medicine (Baltimore) ; 100(21): e25947, 2021 May 28.
Article in English | MEDLINE | ID: mdl-34032704

ABSTRACT

ABSTRACT: To compare the speed of propagation of ultrasound (US) waves (SoS) of the lower leg with the clinical reference standard computed tomography (CT) at the level of lumbar vertebra 3 (L3) for muscle loss assessment. Both calf muscles of 50 patients scheduled for an abdominal CT were prospectively examined with ultrasound. A plexiglas-reflector located on the opposite side of the probe with the calf in between was used as a timing reference for SoS (m/s). CT measurements were performed at the level of L3 and included area (cm2) and attenuation (HU) of the psoas muscle, abdominal muscles, subcutaneous fat, visceral fat and abdominal area. Correlations between SoS, body mass index (BMI) and CT were determined using Pearson's correlation coefficient. Based on reported CT sarcopenia threshold values, receiver operating characteristic (ROC) analysis was performed for SoS. Inter-examiner agreement was assessed with the median difference, inter-quartile range (IQR) and intraclass correlation coefficients. SoS of the calf correlated moderately with abdominal muscle attenuation (r = 0.48; P < .001), psoas muscle attenuation (r = 0.40; P < .01), abdominal area (r = -0.44; P < .01) and weakly with subcutaneous fat area (r = -0.37; P < .01). BMI correlated weakly with psoas attenuation (r = -0.28; P < .05) and non-significantly with abdominal muscle attenuation. Normalization with abdominal area resulted in moderate correlations with abdominal muscle area for SoS (r = 0.43; P < .01) and BMI (r = -0.46; P < .001). Based on sarcopenia threshold values for skeletal muscle attenuation (SMRA), area under curve (AUC) for SoS was 0.724. Median difference between both examiners was -3.4 m/s with IQR = 15.1 m/s and intraclass correlation coefficient = 0.794. SoS measurements of the calf are moderately accurate based on CT sarcopenia threshold values, thus showing potential for muscle loss quantification.


Subject(s)
Leg/diagnostic imaging , Muscle, Skeletal/diagnostic imaging , Sarcopenia/diagnosis , Aged , Aged, 80 and over , Body Mass Index , Female , Humans , Intra-Abdominal Fat/diagnostic imaging , Intra-Abdominal Fat/physiopathology , Leg/physiopathology , Lumbar Vertebrae , Male , Middle Aged , Muscle, Skeletal/physiopathology , Prospective Studies , ROC Curve , Reference Values , Sarcopenia/physiopathology , Subcutaneous Fat/diagnostic imaging , Subcutaneous Fat/physiopathology , Time Factors , Tomography, X-Ray Computed , Ultrasonography
5.
Int J Obes (Lond) ; 45(8): 1811-1820, 2021 08.
Article in English | MEDLINE | ID: mdl-33993191

ABSTRACT

BACKGROUND: Excessive adiposity provides an inflammatory environment. However, in people with severe obesity, how systemic and local adipose tissue (AT)-derived cytokines contribute to worsening glucose tolerance is not clear. METHODS: Ninty-two severely obese (SO) individuals undergoing bariatric surgery were enrolled and subjected to detailed clinical phenotyping. Following an oral glucose tolerance test, participants were included in three groups, based on the presence of normal glucose tolerance (NGT), impaired glucose tolerance (IGT), or type 2 diabetes (T2D). Serum and subcutaneous AT (SAT) biopsies were obtained and mesenchymal stem cells (MSCs) were isolated, characterized, and differentiated in adipocytes in vitro. TNFA and PPARG mRNA levels were determined by qRT-PCR. Circulating, adipocyte- and MSC-released cytokines, chemokines, and growth factors were assessed by multiplex ELISA. RESULTS: Serum levels of IL-9, IL-13, and MIP-1ß were increased in SO individuals with T2D, as compared with those with either IGT or NGT. At variance, SAT samples obtained from SO individuals with IGT displayed levels of TNFA which were threefold higher compared to those with NGT, but not different from those with T2D. Elevated levels of TNFα were also found in differentiated adipocytes, isolated from the SAT specimens of individuals with IGT and T2D, compared to those with NGT. Consistent with the pro-inflammatory milieu, IL-1ß and IP-10 secretion was significantly higher in adipocytes from individuals with IGT and T2D. Moreover, increased levels of TNFα, both mRNA and secreted protein were detected in MSCs obtained from IGT and T2D, compared to NGT SO individuals. Exposure of T2D and IGT-derived MSCs to the anti-inflammatory flavonoid quercetin reduced TNFα levels and was paralleled by a significant decrease of the secretion of inflammatory cytokines. CONCLUSION: In severe obesity, enhanced SAT-derived inflammatory phenotype is an early step in the progression toward T2D and maybe, at least in part, attenuated by quercetin.


Subject(s)
Cytokines/metabolism , Glucose Intolerance/metabolism , Obesity, Morbid , Quercetin/pharmacology , Subcutaneous Fat , Adult , Blood Glucose/drug effects , Cells, Cultured , Female , Glucose Tolerance Test , Humans , Male , Middle Aged , Obesity, Morbid/metabolism , Obesity, Morbid/physiopathology , Subcutaneous Fat/cytology , Subcutaneous Fat/drug effects , Subcutaneous Fat/metabolism , Subcutaneous Fat/physiopathology , Young Adult
6.
Circ Res ; 128(7): 951-968, 2021 04 02.
Article in English | MEDLINE | ID: mdl-33793327

ABSTRACT

Cardiovascular diseases are the leading cause of death worldwide. Overweight and obesity are strongly associated with comorbidities such as hypertension and insulin resistance, which collectively contribute to the development of cardiovascular diseases and resultant morbidity and mortality. Forty-two percent of adults in the United States are obese, and a total of 1.9 billion adults worldwide are overweight or obese. These alarming numbers, which continue to climb, represent a major health and economic burden. Adipose tissue is a highly dynamic organ that can be classified based on the cellular composition of different depots and their distinct anatomical localization. Massive expansion and remodeling of adipose tissue during obesity differentially affects specific adipose tissue depots and significantly contributes to vascular dysfunction and cardiovascular diseases. Visceral adipose tissue accumulation results in increased immune cell infiltration and secretion of vasoconstrictor mediators, whereas expansion of subcutaneous adipose tissue is less harmful. Therefore, fat distribution more than overall body weight is a key determinant of the risk for cardiovascular diseases. Thermogenic brown and beige adipose tissue, in contrast to white adipose tissue, is associated with beneficial effects on the vasculature. The relationship between the type of adipose tissue and its influence on vascular function becomes particularly evident in the context of the heterogenous phenotype of perivascular adipose tissue that is strongly location dependent. In this review, we address the abnormal remodeling of specific adipose tissue depots during obesity and how this critically contributes to the development of hypertension, endothelial dysfunction, and vascular stiffness. We also discuss the local and systemic roles of adipose tissue derived secreted factors and increased systemic inflammation during obesity and highlight their detrimental impact on cardiovascular health.


Subject(s)
Adipose Tissue/physiopathology , Cardiovascular Diseases/etiology , Obesity/physiopathology , Adipose Tissue/metabolism , Adipose Tissue/pathology , Adiposity/physiology , Animals , Blood Pressure/physiology , Blood Vessels/pathology , Heart Disease Risk Factors , Homeostasis/physiology , Humans , Hypertension , Inflammation/etiology , Insulin Resistance , Intra-Abdominal Fat/physiopathology , Mice , Overweight , Subcutaneous Fat/physiopathology , Vascular Diseases/etiology , Vascular Stiffness/physiology , Vasoconstriction/physiology
7.
J Hum Nutr Diet ; 34(3): 585-594, 2021 06.
Article in English | MEDLINE | ID: mdl-33491826

ABSTRACT

BACKGROUND: The influence of body composition changes during neoadjuvant treatment (NT) on long-term survival in patients with gastric cancer (GC) undergoing radical gastrectomy remains unclear. The present study aimed to explore the association between changes in body composition during NT and survival in patients with GC. METHODS: GC patients treated with NT and radical gastrectomy between 2015 and 2018 were included in this retrospective study. Skeletal muscle mass, visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were measured by computer tomography before and after NT. Body composition changes during NT were compared with Kaplan-Meier curves. Univariate and multivariate regression analyses were applied to determine the predictors of overall survival (OS) and disease-free survival (DFS). RESULTS: In total, 157 GC patients were studied. A marked loss of adipose tissue was associated with poor nutritional status. The median follow-up time for all patients was 25 months. Patients with marked VAT loss (≥ 35.7%) during NT had significantly shorter OS (p = 0.028) and DFS (p = 0.03). Similarly, poorer OS (p = 0.033) and DFS (p = 0.003) were observed in patients with marked SAT loss (≥ 30.1%) during NT. Changes in skeletal muscle mass and body weight during NT were not associated with survival. Marked VAT loss accompanied by marked SAT loss was an independent predictor of OS (hazards ratio = 2.447; p = 0.045) and DFS (hazards ratio = 2.674; p = 0.018). CONCLUSIONS: Patients with locally advanced GC have a worse survival when they experienced marked loss of adipose tissue during NT.


Subject(s)
Adenocarcinoma/therapy , Adipose Tissue/physiopathology , Body Composition , Neoadjuvant Therapy/adverse effects , Stomach Neoplasms/therapy , Aged , China/epidemiology , Cohort Studies , Female , Gastrectomy/adverse effects , Humans , Intra-Abdominal Fat/physiopathology , Male , Middle Aged , Nutritional Status , Prognosis , Retrospective Studies , Subcutaneous Fat/physiopathology , Survival Analysis
8.
Ther Apher Dial ; 25(3): 290-295, 2021 Jun.
Article in English | MEDLINE | ID: mdl-32681687

ABSTRACT

We examined the effects of age and sex on the relationship between body fat area and kidney events. We included 367 chronic kidney disease patients between 2011 and 2017. Patients' median age was 73.0 years; 262 (71.4%) patients were male. The median estimated glomerular filtration rate was 20.2 mL/min/1.73 m2 . During the observation period, 187 patients developed kidney events. In males aged <75 years, high subcutaneous fat area was a risk factor for kidney events (hazard ratio: 1.06, 95% CI: 1.02-1.11). In females aged <75 years, high visceral fat area reduced kidney events (hazard ratio: 0.83, 95% CI: 0.71-0.97). In males and females ≥75 years, visceral fat area and subcutaneous fat area were not associated with kidney events. Body fat area was not a risk factor for chronic kidney disease progression in elderly patients. Opposite effects, in sex-related body fat and kidney events, were shown in young patients.


Subject(s)
Intra-Abdominal Fat/physiopathology , Renal Insufficiency, Chronic/physiopathology , Subcutaneous Fat/physiopathology , Age Factors , Aged , Aged, 80 and over , Female , Glomerular Filtration Rate/physiology , Humans , Kidney/physiopathology , Male , Middle Aged , Retrospective Studies , Risk Assessment , Sex Factors
9.
J Urol ; 205(1): 122-128, 2021 Jan.
Article in English | MEDLINE | ID: mdl-32718204

ABSTRACT

PURPOSE: Evidence suggests that visceral fat quantity may be associated with post-prostatectomy outcomes and risk of prostate cancer related death. We evaluated whether increased fat volume, normalized to prostate size, is associated with decreased risk of disease progression. MATERIALS AND METHODS: Patients enrolled on a prospective active surveillance trial for at least 6 months who had magnetic resonance imaging within 2 years of enrollment were eligible. The surveillance protocol included a standardized followup regimen consisting of biennial prostate specific antigen and examination and yearly biopsy. Clinicopathological characteristics were collected at baseline. Three fat measurements were taken using prostate magnetic resonance imaging, including subcutaneous, linear periprostatic (pubic symphysis to prostate) and volumetrically defined periprostatic. Progression was defined as increase in Gleason grade group. Multivariable Cox proportional hazards models were used to evaluate fat volumes normalized by prostate size (stratified into tertiles). RESULTS: A total of 175 patients were included in the study. Average age was 62.5 years (SD 7.4) and average prostate specific antigen was 5.4 ng/dl (SD 3.9). Median followup was 42 months (IQR 18-60) and 50 patients (28.6%) had progression. Compared to the lowest tertile, the highest tertile of volumetric periprostatic fat measurement (HR 2.63, 95% CI 1.23-5.60, p=0.01) and linear periprostatic fat measurement (HR 2.30, 95% CI 1.01-5.22, p=0.05) were associated with worsened progression-free survival, while subcutaneous fat measurement (p=0.97) was not. Importantly, the model did not substantively change when accounting for patient body mass index and other factors. CONCLUSIONS: Increased periprostatic fat volume, normalized to prostate size, may be associated with shortened progression-free survival in men with prostate cancer on active surveillance.


Subject(s)
Adiposity/physiology , Intra-Abdominal Fat/physiopathology , Prostate/pathology , Prostatic Neoplasms/mortality , Watchful Waiting/statistics & numerical data , Aged , Biopsy/statistics & numerical data , Disease Progression , Follow-Up Studies , Humans , Intra-Abdominal Fat/diagnostic imaging , Kallikreins/blood , Magnetic Resonance Imaging/statistics & numerical data , Male , Middle Aged , Neoplasm Grading , Organ Size , Progression-Free Survival , Prospective Studies , Prostate/diagnostic imaging , Prostate-Specific Antigen/blood , Prostatic Neoplasms/blood , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/pathology , Risk Assessment/methods , Risk Assessment/statistics & numerical data , Subcutaneous Fat/diagnostic imaging , Subcutaneous Fat/physiopathology
10.
Nutr Metab Cardiovasc Dis ; 31(2): 532-539, 2021 02 08.
Article in English | MEDLINE | ID: mdl-33153859

ABSTRACT

BACKGROUND AND AIMS: An increased amount of visceral adipose tissues has been related to atherosclerosis and future cardiovascular events. The present study aims to investigate how the abdominal fat distribution links to plasma levels of cardiovascular-related proteins. METHOD AND RESULTS: In the Prospective investigation of Obesity, Energy and Metabolism (POEM) study (n = 326, all aged 50 years), abdominal visceral (VAT) and subcutaneous (SAT) adipose tissue volumes were quantified by MRI. Eighty-six cardiovascular-related proteins were measured by the proximity extension assay (PEA). Similar investigations were carried out in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (n = 400, all aged 75 years). In the discovery dataset (POEM), 10 proteins were related to the VAT/SAT-ratio using false discovery rate <.05. Of those, Cathepsin D (CTSD), Interleukin-1 receptor antagonist protein (IL-1RA) and Growth hormone (GH) (inversely) were related to the VAT/SAT-ratio in the validation in PIVUS following adjustment for sex, BMI, smoking, education level and exercise habits (p < 0.05). In a secondary analysis, a meta-analysis of the two samples suggested that 15 proteins could be linked to the VAT/SAT-ratio following adjustment as above and Bonferroni-correction of the p-value. CONCLUSION: Three cardiovascular-related proteins, cathepsin D, IL-1RA and growth hormone, were being associated with the distribution of abdominal adipose tissue using a discovery/validation approach. A meta-analysis of the two samples suggested that also a number of other cardiovascular-related proteins could be associated with an unfavorable abdominal fat distribution.


Subject(s)
Abdominal Fat/physiopathology , Adiposity , Cardiovascular Diseases/blood , Cathepsin D/blood , Human Growth Hormone/blood , Interleukin 1 Receptor Antagonist Protein/blood , Obesity, Abdominal/physiopathology , Subcutaneous Fat/physiopathology , Abdominal Fat/diagnostic imaging , Aged , Biomarkers/blood , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Female , Heart Disease Risk Factors , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Obesity, Abdominal/diagnostic imaging , Obesity, Abdominal/epidemiology , Prognosis , Prospective Studies , Risk Assessment , Subcutaneous Fat/diagnostic imaging , Sweden/epidemiology
11.
Clin Nutr ; 40(3): 956-965, 2021 03.
Article in English | MEDLINE | ID: mdl-32665100

ABSTRACT

BACKGROUND & AIMS: Blood loss during liver transplantation (LT) is one of the major concerns of the transplant team, given the potential negative post-transplant outcomes related to it. Blood loss was reported to be higher in certain body compositions, such as obese patients, undergoing LT. Therefore, we aimed to study the risk factors for high blood loss (HBL) during adult living donor liver transplant (ALDLT) including the body composition markers; visceral-to-subcutaneous adipose tissue area ratio (VSR), skeletal muscle index and intramuscular adipose tissue content. In June 2015, an aggressive perioperative rehabilitation and nutritional therapy (APRNT) program was prescribed in our institute for the patients with abnormal body composition. METHODS: We retrospectively analyzed 394 patients who had undergone their first ALDLT between 2006 and 2019. Risk factors for HBL were analyzed in the total cohort. Differences in blood loss and risk factors were analyzed in relation to the APRNT. RESULTS: Multivariate risk factor analysis in the total cohort showed that a high VSR (odds ratio (OR): 1.98, 95% confidence interval (CI): 1.19-3.29, P = 0.009), was an independent risk factor for HBL during ALDLT, as well as a history of upper abdominal surgery, simultaneous splenectomy and the presence of a large amount of ascites. After the introduction of the APRNT, a significantly lower blood loss was observed during the ALDLT recipient operation (P = 0.003). Moreover, the significant difference in blood loss observed between normal and high VSR groups before the application of the APRNT (P < 0.001), was not observed with the APRNT (P = 0.85). Likewise, before the APRNT, only high VSR was a risk factor for HBL by multivariate analysis (OR: 2.34, CI: 1.33-4.09, P = 0.003). Whereas with the APRNT, high VSR was no longer a significant risk factor for HBL even by univariate analysis (OR: 0.89, CI: 0.26-3.12, P = 0.86). CONCLUSION: Increased visceral adiposity was an independent risk factor for high intraoperative blood loss during ALDLT recipient operation. With APRNT, high VSR was not associated with high blood loss. Therefore, APRNT might have mitigated the risk of high blood loss related to high visceral adiposity.


Subject(s)
Adiposity , Blood Loss, Surgical/prevention & control , Intra-Abdominal Fat/physiopathology , Liver Transplantation/adverse effects , Nutrition Therapy/methods , Preoperative Care/methods , Adolescent , Adult , Aged , Blood Loss, Surgical/physiopathology , Body Composition , Female , Humans , Liver Transplantation/methods , Living Donors , Male , Middle Aged , Muscle, Skeletal/physiopathology , Odds Ratio , Preoperative Exercise , Retrospective Studies , Risk Factors , Subcutaneous Fat/physiopathology , Treatment Outcome , Young Adult
12.
J Cell Physiol ; 236(2): 900-910, 2021 02.
Article in English | MEDLINE | ID: mdl-32617979

ABSTRACT

This study investigated whether regulation of the renin-angiotensin system (RAS) by enalapril and/or aerobic exercise training (AET) causes browning of the subcutaneous white adipose tissue (sWAT). C57BL/6 mice were fed either a standard chow or a high-fat (HF) diet for 16 weeks. At Week 8, HF-fed animals were divided into sedentary (HF), enalapril (HF-E), AET (HF-T), and enalapril plus AET (HF-ET) groups. Subsequently, sWAT was extracted for morphometry, determination of RAS expression, and biomarkers of WAT browning. The HF group displayed adipocyte hypertrophy and induction of the classical RAS axis. Conversely, all interventions reduced adiposity and induced the counterregulatory RAS axis. However, only AET raised plasma irisin, increased peroxisome proliferator-activated receptor-γ coactivator-1α, and uncoupling protein-1 levels, and the expression of PR-domain containing 16 in sWAT. Therefore, we concluded that AET-induced sWAT browning was independent of the counterregulatory axis shifting of RAS in HF diet-induced obesity.


Subject(s)
Adipose Tissue, Brown/drug effects , Adipose Tissue, Brown/physiopathology , Adiposity/drug effects , Enalapril/pharmacology , Physical Conditioning, Animal/physiology , Running/physiology , Subcutaneous Fat/drug effects , Adipose Tissue, Brown/metabolism , Adipose Tissue, White/metabolism , Adipose Tissue, White/physiopathology , Animals , Biomarkers/metabolism , Diet, High-Fat/adverse effects , Male , Mice , Mice, Inbred C57BL , Obesity/metabolism , Obesity/physiopathology , Renin-Angiotensin System/drug effects , Subcutaneous Fat/metabolism , Subcutaneous Fat/physiopathology
13.
PLoS One ; 15(11): e0242582, 2020.
Article in English | MEDLINE | ID: mdl-33201936

ABSTRACT

In alcoholic liver cirrhosis (LC) patients, obesity has become a problem that progresses into liver dysfunction. Herein, we investigated the relationship between the prognosis of steatohepatitis and body weight, along with fat accumulation in patients with alcoholic LC. We conducted a single-center retrospective study, enrolled 104 alcoholic LC patients without hepatocellular carcinoma (HCC) based on histological and clinical evidence, and investigated factors related to poor prognosis using multivariate Cox regression and cluster analyses. Cox regression analysis revealed three independent relevant factors: subcutaneous adipose tissue (SAT) index (median 34.8 cm2/m2, P = 0.009, hazard ratio [HR] 1.017, 95% confidence interval [CI] 1.004-1.030), total bilirubin level (median 1.7 mg/dL, P = 0.003, HR 1.129, 95% CI 1.042-1.223), and prothrombin time value (median 64%, P = 0.007, HR 0.967, 95% CI 0.943-0.991). In the cluster analysis, we categorized the patients into three groups: no adipose tissue accumulation (NAT group), SAT prior accumulation (SAT group), and visceral adipose tissue prior accumulation (VAT group). The results of the three groups revealed that the SAT group displayed a significantly poor prognosis of the Kaplan-Meier curve (67.1 vs 21.2 vs 65.3, P<0.001) of a 5-year survival rate. Propensity score matching analysis of the SAT and VAT groups was performed to adjust the patient's background, but no significant differences were found between them; however, the prognosis was poorer (21.2 vs 66.3, P<0.001), and hemostatic factors were still at a lower level in the SAT group. These findings suggest that SAT accumulation type of obesity is a poor prognostic factor in alcoholic LC patients without HCC, and the hemorrhagic tendency might worsen the poor prognosis in such cases.


Subject(s)
Liver Cirrhosis, Alcoholic/mortality , Obesity/physiopathology , Subcutaneous Fat/physiopathology , Adipose Tissue/metabolism , Adult , Female , Humans , Intra-Abdominal Fat/metabolism , Liver Cirrhosis, Alcoholic/physiopathology , Male , Middle Aged , Obesity/complications , Prognosis , Proportional Hazards Models , Retrospective Studies , Risk Factors
14.
Cell Rep ; 33(1): 108223, 2020 10 06.
Article in English | MEDLINE | ID: mdl-33027655

ABSTRACT

Overweight and obesity are associated with type 2 diabetes, non-alcoholic fatty liver disease, cardiovascular disease and cancer, but all fat is not equal, as storing excess lipid in subcutaneous white adipose tissue (SWAT) is more metabolically favorable than in visceral fat. Here, we uncover a critical role for mTORC2 in setting SWAT lipid handling capacity. We find that subcutaneous white preadipocytes differentiating without the essential mTORC2 subunit Rictor upregulate mature adipocyte markers but develop a striking lipid storage defect resulting in smaller adipocytes, reduced tissue size, lipid re-distribution to visceral and brown fat, and sex-distinct effects on systemic metabolic fitness. Mechanistically, mTORC2 promotes transcriptional upregulation of select lipid metabolism genes controlled by PPARγ and ChREBP, including genes that control lipid uptake, synthesis, and degradation pathways as well as Akt2, which encodes a major mTORC2 substrate and insulin effector. Further exploring this pathway may uncover new strategies to improve insulin sensitivity.


Subject(s)
Adipose Tissue, White/physiopathology , Lipid Metabolism/physiology , Mechanistic Target of Rapamycin Complex 2/metabolism , Obesity/physiopathology , Subcutaneous Fat/physiopathology , Animals , Humans , Mice
15.
Pediatr Surg Int ; 36(12): 1465-1469, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33125551

ABSTRACT

PURPOSE: We report effects of treatment for pectus excavatum (PE) with a Vacuum Bell (VB). MATERIALS AND METHODS: Fifteen patients (13 males and 2 females) undergoing VB therapy over 6 years, aged 6-17 years (mean: 11.1 years), were divided into two Groups: Group 1 (G1), preteenagers (< 13 years); Group 2 (G2), teenagers (≧ 13 years). We retrospectively recorded changes in depth of depression and the Haller index. RESULTS: The depth of depression reduced in 93.3% of 15 patients (mean; 8.7 mm). Minimal change occurred in the Haller index but the subcutaneous fat thickened significantly (11/15 patients). The improvement rate on elevation of the chest wall was better in G1 than G2 (G1: 54.0% vs G2: 51.3%). CONCLUSION: The maximum depth of depression improved in PE patients as a result of thickening of subcutaneous fat. VB is most effective in preteenagers with PE.


Subject(s)
Funnel Chest/physiopathology , Funnel Chest/therapy , Subcutaneous Fat/physiopathology , Adolescent , Child , Female , Humans , Male , Retrospective Studies , Thoracic Wall/physiopathology , Treatment Outcome , Vacuum
16.
Dermatol Surg ; 46 Suppl 1: S77-S85, 2020 10.
Article in English | MEDLINE | ID: mdl-32976174

ABSTRACT

BACKGROUND: The etiology of cellulite is unclear. Treatment of cellulite has targeted adipose tissue, dermis, and fibrous septae with varying degrees of success and durability of response. OBJECTIVE: Results from clinical trials that target different anatomical aspects of cellulite can provide insights into the underlying pathophysiology of cellulite. MATERIALS AND METHODS: A search of the PubMed database and ClinicalTrials.gov website was conducted to identify clinical trials that have investigated treatments for cellulite. RESULTS: A lack of trial protocol standardization, objective means for quantification of improvement and reported cellulite severity, and short-term follow-up, as well as variation in assessment methods have made comparisons among efficacy studies challenging. However, the lack of durable efficacy and inconsistency seen in clinical results suggest that dermal or adipose tissue changes are not the primary etiologies of cellulite. Clinical studies targeting the collagen-rich fibrous septae in cellulite dimples through mechanical, surgical, or enzymatic approaches suggest that targeting fibrous septae is the strategy most likely to provide durable improvement of skin topography and the appearance of cellulite. CONCLUSION: The etiology of cellulite has not been completely elucidated. However, there is compelling clinical evidence that fibrous septae play a central role in the pathophysiology of cellulite.


Subject(s)
Aponeurosis/physiopathology , Cellulite/etiology , Cellulite/therapy , Buttocks , Cellulite/physiopathology , Clinical Trials as Topic , Extracorporeal Shockwave Therapy , Humans , Lipectomy , Massage , Microbial Collagenase/administration & dosage , Muscle, Skeletal/physiopathology , Phototherapy/methods , Radiofrequency Therapy , Skin/physiopathology , Skin Cream/administration & dosage , Subcutaneous Fat/physiopathology , Thigh , Treatment Outcome
17.
Exp Clin Transplant ; 18(6): 682-688, 2020 11.
Article in English | MEDLINE | ID: mdl-32799787

ABSTRACT

OBJECTIVES: Our aim was to investigate effects of surgery on living donors' body composition and clarify factors related to it. MATERIALS AND METHODS: We evaluated preoperative computed tomography images of 335 living kidney donors (127 men, 209 women) to calculate 3 body composition parameters and changes with aging by sex: (1) skeletal muscle mass, quantified by skeletal muscle index; (2) fat distribution, calculated by visceral adipose tissue/subcutaneous adipose tissue ratio; and (3) muscle quality, quantified by intramuscular adipose tissue content. Thereafter, with pre- and postoperative computed tomography images from 75 living kidney donors (25 men, 50 women) after hand-assisted laparoscopic donor nephrectomy, we compared pre- and postoperative body composition changes. RESULTS: Annual change in intramuscular adipose tissue content with age was 0.0049 in men and 0.0091 in women. Of 75 patients, 49 had lower quality of muscle, intramuscular adipose tissue content was significantly higher after nephrectomy (P < .001), and median change in intramuscular adipose tissue content was 0.061 (range, 0.018-0.11) in men and 0.052 (range, 0.017-0.18) in women. Univariate analysis revealed that skeletal mass index and visceral adipose tissue/subcutaneous adipose tissue ratio changes were significantly different between the intramuscular adipose tissue content improvement and deterioration groups. Multivariate analysis revealed skeletal mass index change was an independent factor for intramuscular adipose tissue content change (P = .0019). Intramuscular adipose tissue content change was negatively correlated with skeletal mass index change (r = -0.40). CONCLUSIONS: Although muscle quality deteriorates after nephrectomy, maintaining muscle mass is important to retaining muscle quality.


Subject(s)
Adiposity , Hand-Assisted Laparoscopy/adverse effects , Intra-Abdominal Fat/physiopathology , Kidney Transplantation/adverse effects , Living Donors , Muscle, Skeletal/physiopathology , Nephrectomy/adverse effects , Postoperative Complications/physiopathology , Subcutaneous Fat/physiopathology , Adult , Aged , Female , Humans , Intra-Abdominal Fat/diagnostic imaging , Male , Middle Aged , Muscle, Skeletal/diagnostic imaging , Postoperative Complications/diagnostic imaging , Postoperative Complications/etiology , Retrospective Studies , Risk Factors , Subcutaneous Fat/diagnostic imaging , Time Factors , Tomography, X-Ray Computed , Treatment Outcome
18.
Obesity (Silver Spring) ; 28(11): 2040-2048, 2020 11.
Article in English | MEDLINE | ID: mdl-32677752

ABSTRACT

OBJECTIVE: This study aimed to assess the association between adipose tissue distribution and severity of clinical course in patients with severe acute respiratory syndrome coronavirus 2. METHODS: For this retrospective study, 143 hospitalized patients with confirmed coronavirus disease 2019 (COVID-19) who underwent an unenhanced abdominal computed tomography (CT) scan between January 1, 2020, and March 30, 2020, were included. Univariate and multivariate logistic regression analyses were performed to identify the risk factors associated with the severity of COVID-19 infection. RESULTS: There were 45 patients who were identified as critically ill. High visceral to subcutaneous adipose tissue area ratio (called visceral adiposity) (odds ratio: 2.47; 95% CI: 1.05-5.98, P = 0.040) and low mean attenuation of skeletal muscle (called high intramuscular fat [IMF] deposition) (odds ratio: 11.90; 95% CI: 4.50-36.14; P < 0.001) were independent risk factors for critical illness. Furthermore, visceral adiposity or high IMF deposition increased the risk of mechanical ventilation (P = 0.013, P < 0.001, respectively). High IMF deposition increased the risk of death (P = 0.012). CONCLUSIONS: COVID-19 patients with visceral adiposity or high IMF deposition have higher risk for critical illness. Therefore, patients with abdominal obesity should be monitored more carefully when hospitalized.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/complications , Obesity, Abdominal/complications , Pneumonia, Viral/complications , Subcutaneous Fat/physiopathology , Adiposity/physiology , Aged , COVID-19 , Critical Illness , Female , Humans , Male , Middle Aged , Pandemics , Retrospective Studies , Risk Factors , SARS-CoV-2
19.
Nutr Metab Cardiovasc Dis ; 30(8): 1306-1314, 2020 07 24.
Article in English | MEDLINE | ID: mdl-32507340

ABSTRACT

BACKGROUND AND AIMS: In the present study, we assessed the extent of mediation by low-grade systemic inflammation and adipokines in the association between abdominal adiposity and insulin resistance. METHODS AND RESULTS: In this cross-sectional analysis of baseline measurements of the Netherlands Epidemiology of Obesity study, total body fat (TBF) was measured in all (n = 5772) participants who did not have missing data and neither used glucose-lowering medication, and abdominal subcutaneous adipose tissue (aSAT) and visceral adipose tissue (VAT) were assessed by MRI in a random subgroup (n = 2448). C-reactive protein (CRP), adiponectin, and leptin were considered as potential mediators, and insulin resistance was assessed by Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Mediation by CRP, adiponectin, and leptin was studied by including the mediators to the fully adjusted linear regression model. Participants had a mean (SD) age of 56 (6) years, TBF of 36 (9) %, VAT of 119 (61) cm2 and aSAT of 300 (111) cm2. Per SD of TBF, VAT and aSAT, HOMA-IR was 64% (95% confidence interval [CI]: 59-70), 33% (95%CI: 28-42) and 20% (95%CI: 14-26) higher, respectively. The association between aSAT and HOMA-IR fully disappeared after adjustment for leptin; the association between VAT and HOMA-IR attenuated after adjustment for leptin (22%) and adiponectin (15%). No mediation was observed by CRP, and mediation estimates were similar in men and women. CONCLUSION: Where leptin fully explained the aSAT-HOMA-IR association, the VAT-HOMA-IR association was only partly explained by leptin and adiponectin similarly in men and women.


Subject(s)
Adiponectin/blood , C-Reactive Protein/metabolism , Insulin Resistance , Intra-Abdominal Fat/metabolism , Leptin/blood , Obesity, Abdominal/blood , Subcutaneous Fat/metabolism , Adiposity , Age Factors , Biomarkers/blood , Cross-Sectional Studies , Female , Humans , Intra-Abdominal Fat/diagnostic imaging , Intra-Abdominal Fat/physiopathology , Magnetic Resonance Imaging , Male , Middle Aged , Netherlands/epidemiology , Obesity, Abdominal/diagnosis , Obesity, Abdominal/epidemiology , Obesity, Abdominal/physiopathology , Prospective Studies , Risk Factors , Subcutaneous Fat/diagnostic imaging , Subcutaneous Fat/physiopathology
20.
Nutrients ; 12(5)2020 May 12.
Article in English | MEDLINE | ID: mdl-32408709

ABSTRACT

Protein Energy Wasting (PEW) in hemodialysis (HD) patients is a multifactorial condition due to specific pathology-related pathogenetic mechanisms, leading to loss of skeletal muscle mass in HD patients. Computed Tomography and Magnetic Resonance Imaging still represent the gold standard techniques for body composition assessment. However, their widespread application in clinical practice is difficult and body composition evaluation in HD patients is mainly based on conventional anthropometric nutritional indexes and bioelectrical impedance vector analysis (BIVA). Little data is currently available on ultrasound (US)-based measurements of muscle mass and fat tissue in this clinical setting. The purpose of our study is to ascertain: (1) if there are differences between quadriceps rectus femoris muscle (QRFM) thickness and abdominal/thigh subcutaneous fat tissue (SFT) measured by US between HD patients and healthy subjects; (2) if there is any correlation between QRFM and abdominal/thigh SFT thickness by US, and BIVA/conventional nutritional indexes in HD patients. We enrolled 65 consecutive HD patients and 33 healthy subjects. Demographic and laboratory were collected. The malnutrition inflammation score (MIS) was calculated. Using B-mode US system, the QRFM and SFT thicknesses were measured at the level of three landmarks in both thighs (superior anterior iliac spine, upper pole of the patella, the midpoint of the tract included between the previous points). SFT was also measured at the level of the periumbilical point. The mono frequency (50 KHz) BIVA was conducted using bioelectrical measurements (Rz, resistance; Xc, reactance; adjusted for height, Rz/H and Xc/H; PA, phase angle). 58.5% were men and the mean age was 69 (SD 13.7) years. QRFM and thigh SFT thicknesses were reduced in HD patients as compared to healthy subjects (p < 0.01). Similarly, also BIVA parameters, expression of lean body mass, were lower (p < 0.001), except for Rz and Rz/H in HD patients. The average QRFM thickness of both thighs at top, mid, lower landmarks were positively correlated with PA and body cell mass (BCM) by BIVA, while negatively correlated with Rz/H (p < 0.05). Abdominal SFT was positively correlated with PA, BCM and basal metabolic rate (BMR) (p < 0.05). Our study shows that ultrasound QRFM and thigh SFT thicknesses were reduced in HD patients and that muscle ultrasound measurements were significantly correlated with BIVA parameters.


Subject(s)
Kidney Failure, Chronic/diagnostic imaging , Quadriceps Muscle/diagnostic imaging , Renal Dialysis/adverse effects , Subcutaneous Fat/diagnostic imaging , Ultrasonography/statistics & numerical data , Aged , Body Composition , Cross-Sectional Studies , Electric Impedance , Female , Humans , Kidney Failure, Chronic/physiopathology , Kidney Failure, Chronic/therapy , Male , Middle Aged , Quadriceps Muscle/physiopathology , Reproducibility of Results , Subcutaneous Fat/physiopathology
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