Intra-abdominal Adipose Tissue Research Articles

Association between metabolic score of visceral fat and carotid atherosclerosis in Chinese health screening population: a cross-sectional study

BackgroundThe metabolic score for visceral fat (METS-VF) quantifies the cumulative burden of visceral and intra-abdominal adipose tissues. However, the relationship between the METS-VF and carotid atherosclerosis (CAS) has not been extensively explored. Therefore, this study aimed to investigate the association between the METS-VF and CAS.MethodsThis cross-sectional study enrolled 7089 Chinese adults who underwent physical examinations at the Zhenhai Lianhua Hospital, Zhejiang, China, in 2020. Multivariable logistic regression analysis was used to explore the linear relationship between METS-VF and CAS. Generalised additive models (GAM) were employed to evaluate potential nonlinear associations. The inflection points of METS-VF were determined using segmented logistic regression analysis optimised for maximum likelihood ratios and recursive algorithms.ResultsMultivariable logistic regression analysis revealed a positive correlation between METS-VF and CAS (odds ratio [OR]: 1.824, 95% confidence interval [CI]: 1.753–1.899; P < 0.001). The GAM analysis confirmed a nonlinear association between them [effective degrees of freedom: 4.803, χ2: 876.7, P < 0.001], with an inflection point at a METS-VF of 8.09 (P < 0.001 for log-likelihood ratio test). Below this inflection point, METS-VF exhibited a significant positive association with CAS risk (OR: 1.874, 95% CI: 1.796–1.954; P < 0.001). Conversely, no significant association was observed when METS-VF ≥ 8.09 (OR: 0.998, 95% CI: 0.786–1.268; P = 0.989).ConclusionsMETS-VF and CAS demonstrated a positive non-linear correlation, with the curve indicating a saturation effect at METS-VF = 8.09.

Fecal transplant from vaginally seeded infants decreases intraabdominal adiposity in mice

ABSTRACT Exposing C-section infants to the maternal vaginal microbiome, coined “vaginal seeding”, partially restores microbial colonization. However, whether vaginal seeding decreases metabolic disease risk is unknown. Therefore, we assessed the effect of vaginal seeding of human infants on adiposity in a murine model. Germ-free mice were colonized with transitional stool from human infants who received vaginal seeding or control (placebo) seeding in a double-blind randomized trial. There was a reduction in intraabdominal adipose tissue (IAAT) volume in male mice that received stool from vaginally seeded infants compared to control infants. Higher levels of isoleucine and lower levels of nucleic acid metabolites were observed in controls and correlated with increased IAAT. This suggests that early changes in the gut microbiome and metabolome caused by vaginal seeding have a positive impact on metabolic health.

Deletion of SGK1 in Smooth Muscle Cells Induces Sex-specific Differences in Obesity-mediated Metabolic Dysfunction and Adipose Tissue Remodeling

Objectives: Obesity, characterized by an excess of adipose tissue, is an important risk factor for the development of metabolic diseases such as type 2 diabetes. In obesity, poor metabolic health is partly due to glucose intolerance, a condition in which whole-body glucose regulation is impaired. Adipose tissue is an endocrine organ central for optimal metabolic health and its expansion by excessive fat intake induces metabolic dysfunction. The molecular mechanisms that promote metabolic dysfunction in obesity are not fully understood. Adipose tissue function is dependent on the presence of new vascular networks capable of supplying nutrients and oxygen during adipose tissue expansion. Thus, pathological vascular remodeling may promote adipose tissue expansion and dysfunction in obesity. In this regard, our previous studies have shown that serum and glucocorticoid-inducible kinase 1 (SGK1) in vascular smooth muscle cells (vSMCs) mediates pathological vascular remodeling in obesity. SGK1 is a serine/threonine kinase that becomes elevated in the vasculature during obesity and is implicated in the development of metabolic syndrome. Therefore, we hypothesize that smooth muscle cell derived-SGK1 promotes pathological adipose tissue remodeling and metabolic dysfunction during obesity by perturbing adipose tissue vascularization. Methods: To test this hypothesis, these studies utilized our novel SMC-specific SGK1 knockout (smSGK1KO) mouse model to study the influence of SMC-derived SGK1 on adipose tissue remodeling and overall metabolic health in vivo. Male and female 8-week-old smSGK1WT and smSGK1KO mice were subjected to either a 10% low-fat diet (LF) or a high-fat diet (HF) for 8 weeks with weekly body weight measurements. Upon completion of respective diets, mice were subjected to glucose tolerance tests (GTT) to assess glucose tolerance and metabolic health. Adipose tissues from the subcutaneous (inguinal) and intra-abdominal (epididymal/gonadal) white adipose tissue (WAT) depots were harvested to assess overall adiposity and vascularization. Results: Our data show sexual dimorphism exists in the way smSGK1KO mice respond to a chronic high-fat diet. When fed a HF diet, female smSGK1KO mice gained approximately 60% more weight than their female smSGK1WT counterparts. In contrast, weight gain was about 50% lower in male smSGK1KO compared to male smSGK1WT mice on the same HF diet. Despite the differences in weight gain, inguinal and epididymal/gonadal WAT were reduced in male and female smSGK1KO mice fed a HF diet. Surprisingly, GTT was similar between female smSGK1KO and smSGK1WT mice, despite the increased weight gain, while male smSGK1KO mice displayed improvement in glucose tolerance in comparison to their wildtype counterparts. Moreover, male smSGK1KO mice appear to have enhanced vascularization in WAT depots as evidenced by increased vascular branching in fat pads. Conclusions: These studies suggest that SGK1 in smooth muscle cells contributes to adipose tissue remodeling and metabolic dysfunction under obesogenic conditions. Additionally, these studies indicate a need to understand the mechanisms by which crosstalk between the vasculature and adipose tissue modulates obesity and overall metabolic health. This research is supported in part by grant number 5U24DK132733-02 from the National Institute of Health, NIH. This research is supported in part by grant number 5T32HL007609-36 from the National Institute of Health, NIH. This research is supported in part by grant number 2100832 from the National Science Foundation, NSF. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Anti-Obesity Effects of the Larval Powder of Steamed and Lyophilized Mature Silkworms in a Newly Designed Adult Mouse Model.

Recently, "mature" silkworms (MS) of Bombix mori have been considered a potential nutraceutical, with a number of health benefits reported for steamed and lyophilized MS powder (SMSP). However, no obesity-related effects have been reported for SMSP. In the present study, anti-obesity effects of SMSP were investigated in adult mice in vivo, aged 12 weeks at the onset of SMSP treatment, fed a normal diet (ND) and a high-fat diet (HFD), respectively, for 12 weeks. SMSP significantly suppressed body weight gain, intra-abdominal adipose tissue, and food efficiency in both ND-fed and HFD-fed adult mice. In addition, SMSP significantly decreased food intake and liver weight in HFD-fed mice, indicating that SMSP suppressed appetite and simultaneously reduced the conversion of feed into body weight in HFD-fed mice. SMSP also significantly lowered the serum levels of glucose, triglyceride, total cholesterol, low-density lipoprotein cholesterol, asparagine transaminase, alanine transaminase, and alkaline phosphatase. However, SMSP had no significant effect on the weights of the kidney, spleen, or thymus or the serum levels of blood urea nitrogen and creatinine. Taken together, the above results suggest that SMSP has potent anti-obesity effects and is safe for long-term use as a potential therapeutic and/or nutraceutical in both obese patients and non-obese individuals.

Higher Intra-Abdominal Visceral Adipose Tissue Mass Is Associated With Lower Rates of Clinical and Endoscopic Remission in Patients With Inflammatory Bowel Diseases Initiating Biologic Therapy: Results of the Constellation Study

We sought to assess the association between intra-abdominal visceral adipose tissue (IA-VAT) and response to 3 different biologic drugs in patients with inflammatory bowel disease (IBD) and to investigate its effects on inflammatory cytokine expression, pharmacokinetics, and intestinal microbiota. We prospectively enrolled subjects with active IBD initiating infliximab, vedolizumab, or ustekinumab and a healthy control group. Baseline body composition (including IA-VAT as percent of total body mass [IA-VAT%]) was measured using GE iDXA scan. Primary outcome was corticosteroid- free deep remission at weeks 14-16, defined as Harvey Bradshaw Index <5 for Crohn's disease and partial Mayo score <2 for ulcerative colitis, with a normal C-reactive protein and fecal calprotectin. Secondary outcomes were corticosteroid-free deep remission and endoscopic remission (Endoscopic Mayo Score ≤1 in ulcerative colitis or Simple Endoscopic Score for Crohn's disease ≤2) at weeks 30-46. A total of 141 patients with IBD and 51 healthy controls were included. No differences in body composition parameters were seen between the IBD and healthy control cohorts. Patients with higher IA-VAT% were less likely to achieve corticosteroid-free deep remission (P < .001) or endoscopic remission (P= .02) vs those with lower IA-VAT%. Furthermore, nonresponders with high IA-VAT% had significantly higher serum interleukin-6 and tumor necrosis factor at baseline compared with responders and patients with low IA-VAT%. Drug pharmacokinetic properties and microbiota diversity were similar when comparing high and low IA-VAT% groups. Higher IA-VAT% was independently associated with worse outcomes. This association could be driven at least partially by discrete differences in inflammatory cytokine expression.

Effect of Simultaneous Intake of Medium-Chain Triglyceride and d-Allulose on Body Fat Accumulation in Rats Fed a High-Fat Diet

Medium-chain triglycerides, lipids containing three 6−12 carbon medium-chain fatty acids, have antiobesity effects because they do not promote lipogenesis. d-Allulose, a low-calorie epimer of fructose commercially used as a low-calorie sweetener, suppresses hepatic lipogenesis and enhances postprandial fat oxidation. Therefore, we have explored whether a simultaneous intake of medium-chain fatty acids and d-allulose may exhibit a greater reduction in de novo lipogenesis and increase their antiobesity effects. To this end, 32 male Wistar rats were divided into four treatment groups of equal sizes: control, 3% d-allulose-treated, 5% medium-chain triglycerides-treated, and 3% d-allulose + 5% medium-chain triglycerides-treated. After 8 weeks of ad libitum exposure to these diets, d-allulose significantly decreased intra-abdominal adipose tissue and total body fat weight, with or without medium-chain triglyceride supplementation. The antiobesity effect of d-allulose was observed with or without dietary medium-chain triglyceride supplementation in high-fat diet-induced obese rats, but no synergistic effect was detected between d-allulose and medium-chain triglycerides.

Heterogeneity in the effect of marked weight loss on metabolic function in women with obesity.

BACKGROUNDThere is considerable heterogeneity in the effect of weight loss on metabolic function in people with obesity.METHODSWe evaluated muscle and liver insulin sensitivity, body composition, and circulating factors associated with insulin action before and after approximately 20% weight loss in women identified as "Responders" (n = 11) or "Non-responders" (n = 11), defined as the top (>75% increase) and bottom (<5% increase) quartiles of the weight loss-induced increase in glucose disposal rate (GDR) during a hyperinsulinemic-euglycemic clamp procedure, among 43 women with obesity (BMI: 44.1 ± 7.9 kg/m2).RESULTSAt baseline, GDR, which provides an index of muscle insulin sensitivity, and the hepatic insulin sensitivity index were more than 50% lower in Responders than Non-responders, but both increased much more after weight loss in Responders than Non-responders, which eliminated the differences between groups. Weight loss also caused greater decreases in intrahepatic triglyceride content and plasma adiponectin and PAI-1 concentrations in Responders than Non-responders and greater insulin-mediated suppression of plasma free fatty acids, branched-chain amino acids, and C3/C5 acylcarnitines in Non-responders than Responders, so that differences between groups at baseline were no longer present after weight loss. The effect of weight loss on total body fat mass, intra-abdominal adipose tissue volume, adipocyte size, and circulating inflammatory markers were not different between groups.CONCLUSIONThe results from our study demonstrate that the heterogeneity in the effects of marked weight loss on muscle and hepatic insulin sensitivity in people with obesity is determined by baseline insulin action, and reaches a ceiling when "normal" insulin action is achieved.TRIAL REGISTRATIONNCT00981500, NCT01299519, NCT02207777.FUNDINGNIH grants P30 DK056341, P30 DK020579, P30 DK052574, UL1 TR002345, and T32 HL13035, the American Diabetes Association (1-18-ICTS-119), the Longer Life Foundation (2019-011), and the Atkins Philanthropic Trust.

Role of Melatonin in the Onset of Metabolic Syndrome in Women.

Metabolic syndrome (MetS) is a constellation of several associated cardiometabolic risk factors that increase the risk of developing type 2 diabetes mellitus (T2DM), cardiovascular diseases, and mortality. The role of hormonal factors in the development of MetS is assumed. In women, an insulin-resistant state that is associated with polycystic ovarian syndrome and increased deposition of intra-abdominal adipose tissue promotes the development of MetS and increases cardiovascular risk. The neuroendocrine hormone melatonin is secreted mainly at night under the regulatory action of the suprachiasmatic nucleus in the hypothalamus. Melatonin secretion is influenced by exogenous factors such as light and seasons and endogenous factors such as age, sex, and body weight. At present, the role of melatonin in metabolic disorders in humans is not fully understood. In this review, we set out to analyze the relationship of melatonin with the main features of MetS in women. Data from experimental and clinical studies on the role of melatonin in glucose metabolism and on the involvement of melatonin in lipid disturbances in MetS are reviewed. The complex influence of melatonin on hypertension is discussed. The changes in melatonin, leptin, and ghrelin and their relation to various metabolic processes and vascular dysfunction are discussed.

The Link between NAFLD and Metabolic Syndrome.

Metabolic syndrome (MetS) is characterized by an association of cardiovascular and diabetes mellitus type 2 risk factors. Although the definition of MetS slightly differs depending on the society that described it, its central diagnostic criteria include impaired fasting glucose, low HDL-cholesterol, elevated triglycerides levels and high blood pressure. Insulin resistance (IR) is believed to be the main cause of MetS and is connected to the level of visceral or intra-abdominal adipose tissue, which could be assessed either by calculating body mass index or by measuring waist circumference. Most recent studies revealed that IR may also be present in non-obese patients, and considered visceral adiposity to be the main effector of MetS' pathology. Visceral adiposity is strongly linked with hepatic fatty infiltration also known as non-alcoholic fatty liver disease (NAFLD), therefore, the level of fatty acids in the hepatic parenchyma is indirectly linked with MetS, being both a cause and a consequence of this syndrome. Taking into consideration the present pandemic of obesity and its tendency to drift towards a progressively earlier onset due to the Western lifestyle, it leads to an increased NAFLD incidence. Novel therapeutic resources are lifestyle intervention with physical activity, Mediterranean diet, or therapeutic surgical respective metabolic and bariatric surgery or drugs such as SGLT-2i, GLP-1 Ra or vitamin E. NAFLD early diagnosis is important due to its easily available diagnostic tools such as non-invasive tools: clinical and laboratory variables (serum biomarkers): AST to platelet ratio index, fibrosis-4, NAFLD Fibrosis Score, BARD Score, fibro test, enhanced liver fibrosis; imaging-based biomarkers: Controlled attenuation parameter, magnetic resonance imaging proton-density fat fraction, transient elastography (TE) or vibration controlled TE, acoustic radiation force impulse imaging, shear wave elastography, magnetic resonance elastography; and the possibility to prevent its complications, respectively, fibrosis, hepato-cellular carcinoma or liver cirrhosis which can develop into end-stage liver disease.

Effects of acute exercise and exercise training on plasma GDF15 concentrations and associations with appetite and cardiometabolic health in individuals with overweight or obesity – A secondary analysis of a randomized controlled trial

Growth Differentiation Factor 15 (GDF15) is seemingly involved in appetite control. Acute exercise increases GDF15 concentrations in lean humans, but acute and long-term effects of exercise on GDF15 in individuals with overweight/obesity are unknown. We investigated the effects of acute exercise and exercise training on GDF15 concentrations in individuals with overweight/obesity and associations with appetite and cardiometabolic markers. 90 physically inactive adults (20–45 years) with overweight/obesity were randomized to 6-months habitual lifestyle (CON, n=16), or isocaloric exercise of moderate (MOD, n=37) or vigorous intensity (VIG, n=37), 5 days/week. Testing was performed at baseline, 3, and 6 months. Plasma GDF15 concentrations, other metabolic markers, and subjective appetite were assessed fasted and in response to acute exercise before an ad libitum meal. Cardiorespiratory fitness, body composition, insulin sensitivity, and intraabdominal adipose tissue were measured. At baseline, GDF15 increased 18% (95%CI: 4; 34) immediately after acute exercise and 32% (16; 50) 60 min post-exercise. Fasting GDF15 increased 21% (0; 46) in VIG after 3 months (p=0.045), but this attenuated at 6 months (13% (−11; 43), p=0.316) and was unchanged in MOD (11% (−6; 32), p=0.224, across 3 and 6 months). Post-exercise GDF15 did not change in MOD or VIG. GDF15 was not associated with appetite or energy intake. Higher GDF15 was associated with lower cardiorespiratory fitness, central obesity, dyslipidemia, and poorer glycemic control. In conclusion, GDF15 increased in response to acute exercise but was unaffected by exercise training. Higher GDF15 concentrations were associated with a less favorable cardiometabolic profile but not with markers of appetite. This suggests that GDF15 increases in response to acute exercise independent of training state. Whether this has an impact on free-living energy intake and body weight management needs investigation.

Associations of renal sinus fat with blood pressure and ectopic fat in a diverse cohort of adults

BackgroundRenal sinus fat (RSF) is an ectopic fat depot shown to be associated with visceral adiposity and hypertension in predominantly white populations. The purpose of this analysis is to investigate RSF and associations between RSF and blood pressure in a cohort of African American (AA) and European American (EA) adults. A secondary purpose was to explore risk factors associated with RSF. MethodsParticipants were 116 A A and EA adult men and women. Ectopic fat depots were assessed with MRI: RSF, intraabdominal adipose tissue (IAAT), intermuscular adipose tissue (IMAT), perimuscular adipose tissue (PMAT), and liver fat. Cardiovascular measures included diastolic blood pressure (DBP), systolic blood pressure (SBP), pulse pressure, mean arterial pressure, and flow mediated dilation. Matsuda index was calculated for insulin sensitivity. Pearson correlations were used to investigate associations of RSF with cardiovascular measures. Multiple linear regression was used to evaluate contributions of RSF on SBP and DBP and to explore factors associated with RSF. ResultsNo difference was observed in RSF between AA and EA participants. RSF was positively associated with DBP in AA participants, but this was not independent of age and sex. Age, male sex, and total body fat were positively associated with RSF in AA participants. Insulin sensitivity was inversely and IAAT and PMAT were positively associated with RSF in EA participants. ConclusionsDifferential associations of RSF with age, insulin sensitivity, and adipose depots among AA and EA adults suggest unique pathophysiological mechanisms influence RSF deposition, which may contribute to chronic disease etiology and progression.

Effects of Dietary Allitol on Body Fat Accumulation in Rats.

Allitol is a rare sugar alcohol obtained by reducing d-allulose (d-psicose). However, information on the effects of long-term dietary allitol intake is limited. This study aimed to investigate the effect of allitol supplementation, as a sugar substitute, on body fat accumulation in rats compared with sucrose, rare sugar d-allulose, or erythritol. Thirty-two male Wistar rats (3 wk old) were fed experimental diets including 5% sucrose, allitol, erythritol, or d-allulose for 8 wk ad libitum. Weight gain, food intake, and food efficiency did not differ among the groups. The total body fat mass and percentage, and intra-abdominal adipose tissue weights were significantly lower in rats fed with the allitol diet than in those fed with the sucrose diet. These body fat indicators tended to be lower in rats fed with the erythritol and d-allulose diets than in those fed with the sucrose diet, but there was no significant difference. The serum glucose-lowering effect obtained in rats fed with the d-allulose diet did not appear in rats fed with the allitol diet. These results suggest that the anti-obesity effect of allitol may be equal to or greater than that of d-allulose.

Redistribution of adipose tissue is associated with left atrial remodeling and dysfunction in patients with atrial fibrillation.

ObjectiveAdipose tissue is recognized as a crucial regulator of atrial fibrillation (AF). However, the effect of epicardial adipose tissue (EAT) on the pathophysiology of AF might be different from that of other adipose tissues. The purpose of this study was to explore the distribution features of different adipose tissues in AF patients and their relationships with left atrial (LA) remodeling and function.MethodsA total of 205 participants (including 112 AF and 93 non-AF patients) were recruited. Color doppler ultrasound was used to measure the thickness of subcutaneous, extraperitoneal, and intra-abdominal adipose tissue. Cardiac CT scan was performed to measure the mean thickness of EAT surrounding the whole heart (total-EAT) and specific regions, including left atrium (LA-EAT), left ventricle, right ventricle, interventricular groove, and atrioventricular groove. LA anatomical remodeling and function were measured by echocardiography, while electrical remodeling was evaluated by P-wave duration and dispersion using Electrocardiography (obtained after cardioversion or ablation in AF patients). Relationship between the thickness of different adipose tissues and LA remodeling and function was analyzed.ResultsThe thickness of subcutaneous, extraperitoneal, and intra-abdominal adipose tissue was similar between AF and non-AF patients, and had no or only weak association with LA remodeling and dysfunction. However, compared to non-AF participants, total-EAT thickness significantly increased in both paroxysmal and persistent AF patients (non-AF vs. paroxysmal AF vs. persistent AF: 6.31 ± 0.63 mm vs. 6.76 ± 0.79 mm vs. 7.01 ± 1.18 mm, P < 0.001), which was positively correlated with the LA size and P-wave duration and dispersion, and negatively correlated with LA ejection fraction and peak strain rate. More interestingly, EAT thickness in AF patients did not increase uniformly in different regions of the heart. Compared to EAT surrounding the other regions, LA-EAT was found to accumulate more greatly, and had a closer relationship to LA remodeling and dysfunction. Multivariate logistic regression analysis also showed that LA-EAT was significantly correlated with the presence of AF (OR = 4.781; 95% CI 2.589–8.831, P < 0.001).ConclusionRather than other adipose tissues, accumulation and redistribution of EAT, especially surrounding the LA, is associated with LA remodeling and dysfunction in AF patients.

High prevalence of abdominal obesities and metabolically unhealthy individuals in a highly urbanized district of India: findings of a cross-sectional survey in Puducherry.

Abdominal obesities are better markers for predicting cardiovascular abnormalities than risk stratification based only on body mass index (BMI). We aimed to estimate the prevalence of abdominal adiposities using predictive equations for Asian Indian adults and to determine the prevalence of metabolically healthy subjects among those overweight/obese and with normal BMI. A community-based survey was conducted among those aged 18-69 years in the district of Puducherry between February 2019 and February 2020. We surveyed 2,560 individuals selected through multi-stage cluster random sampling from urban and rural areas (50 wards and 50 villages, respectively) of the district. Anthropometric measurements, such as height, weight, waist circumference, and blood pressure were recorded from each participant. Fasting blood sample was collected from each alternate participant to estimate metabolic risk factors. Over four-fifths (85.6%; 95% CI: 84.2-86.9) and two-thirds (69.7%; 95% CI: 67.9-71.6) of the population in the district had high levels of intra-abdominal adipose tissue (IAAT) and total abdominal fat (TAF), respectively. Both the risk factors were significantly higher among women and urban population. About 43% (95% CI: 41-44.9) of the population had high abdominal subcutaneous adipose tissue (SCAT) with a significantly higher prevalence among the urban population. Among those overweight/obese (n = 773), almost all 99.4% (95% CI: 98.7-99.9) were metabolically unhealthy. Among subjects with normal BMI (n = 314), only about 2.9% (95% CI: 1.3-4.8) were metabolically healthy. We highlight the substantially high prevalence of IAAT, TAF, and SCAT in the district of Puducherry. Almost all the study population was metabolically unhealthy irrespective of their BMI levels.

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

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

Association between non-alcoholic fatty liver disease and epicardial adipose tissue volume with cardiometabolic risk in coronary heart disease

BackgroundRegional adiposity has a significant impact on the formation of adverse metabolic and cardiovascular risk profiles. While much of the attention was directed to the importance of intra-abdominal adipose tissue, there were several new investigations about mediastinal and epicardial regions’ visceral adiposity. Our study aimed to determine the association between non-alcoholic fatty liver and increased epicardial adipose tissue mass with coronary artery disease severity.MethodsThis study was conducted on sixty patients who presented with symptoms of coronary artery disease and attended elective coronary angiography to rule out coronary artery disease. All patients have been subjected to full hepatic profile, noninvasive scoring system such as Fibrosis-4 and non-alcoholic fatty liver disease fibrosis score and abdominal ultrasound for diagnosis of non-alcoholic fatty liver disease and trans-thoracic echocardiography for measurement of average epicardial adipose tissue thickness. Student T test, analysis of variance test, chi-square test, and Fisher’s exact test were used for statistical analysis.ResultsAccording to the severity of coronary artery disease, patients with significant coronary stenosis had statistically significant higher degree of hepatic steatosis in abdominal ultrasound (P value < 0.001) while regarding the non-alcoholic fatty liver disease fibrosis score and Fibrosis-4 for non-alcoholic fatty liver disease diagnosis, there was no significance between both groups. Also, the epicardial adipose tissue mean thickness was found to be statistically significantly higher among those with significant coronary stenosis than those without [7.859 ± 0.691 mm versus 5.600 ± 0.386 mm]. Moreover, statistically significant higher epicardial adipose tissue thickness values were found among grade 3 hepatic steatosis than in grades 2, 1, or 0 (P value < 0.001). At a cutoff > 6.1 mm, epicardial adipose tissue thickness was a valuable tool in discrimination between significant and non-significant coronary artery disease with specificity and sensitivity of 100%.ConclusionHigh epicardial adipose tissue thickness may represent a marker of severity of non-alcoholic fatty liver disease as well as an independent predictor of coronary artery disease risk.

Red Rice Bran Extract Attenuates Adipogenesis and Inflammation on White Adipose Tissues in High-Fat Diet-Induced Obese Mice.

Red rice bran extract (RRBE) has been reported to have the potential for in vitro metabolic modulation and anti-inflammatory properties. However, little is known about the molecular mechanisms of these potentials in adipose tissue. This study aimed to evaluate the in vivo anti-adipogenic, anti-hypertrophic, and anti-inflammatory activities of RRBE and its major bioactive compounds in mice. After six weeks of consuming either a low-fat diet or a high-fat diet (HFD), 32 mice with initial body weights of 20.76 ± 0.24 g were randomly divided into four groups; the four groups were fed a low-fat diet, a HFD, a HFD plus 0.5 g/kg of RRBE, or a HFD plus 1 g/kg of RRBE, respectively. The 6-week treatment using RRBE reduced HFD-induced adipocyte hypertrophy, lipid accumulation, and inflammation in intra-abdominal epididymal white adipose tissue (p < 0.05) without causing significant changes in body and adipose tissue weight, which reductions were accompanied by the down-regulated expression of adipogenic and lipid metabolism genes, including CCAAT/enhancer-binding protein-alpha, sterol regulatory element-binding protein-1c, and hormone-sensitive lipase (p < 0.05), as well as inflammatory genes, including macrophage marker F4/80, nuclear factor-kappa B p65, monocyte chemoattractant protein-1, tumor necrosis factor-alpha, and inducible nitric oxide synthase (p < 0.05), in adipose tissue. Furthermore, RRBE significantly decreased serum tumor necrosis factor-alpha levels (p < 0.05). Bioactive compound analyses revealed the presence of phenolics, flavonoids, anthocyanins, and proanthocyanidins in these extracts. Collectively, this study demonstrates that RRBE effectively attenuates HFD-induced pathological adipose tissue remodeling by suppressing adipogenesis, lipid dysmetabolism, and inflammation. Therefore, RRBE may emerge as one of the alternative food products to be used against obesity-associated adipose tissue dysfunction.

Role of the Steroid Sulfate Uptake Transporter Soat (Slc10a6) in Adipose Tissue and 3T3-L1 Adipocytes.

In addition to the endocrine and paracrine systems, peripheral tissues such as gonads, skin, and adipose tissue are involved in the intracrine mechanisms responsible for the formation of sex steroids via the transformation of dehydroepiandrosterone and dehydroepiandrosterone sulfate (DHEA/DHEAS) into potent androgenic and estrogenic hormones. Numerous studies have examined the relationship between overweight, central obesity, and plasma levels of DHEA and DHEAS. The sodium-dependent organic anion transporter Soat (Slc10a6) is a plasma membrane uptake transporter for sulfated steroids. Significantly increased expression of Slc10a6 mRNA has been previously described in organs and tissues of lipopolysaccharide (LPS)-treated mice, including white adipose tissue. These findings suggest that Soat plays a role in the supply of steroids in peripheral target tissues. The present study aimed to investigate the expression of Soat in adipocytes and its role in adipogenesis. Soat expression was analyzed in mouse white intra-abdominal (WAT), subcutaneous (SAT), and brown (BAT) adipose tissue samples and in murine 3T3-L1 adipocytes. In addition, adipose tissue mass and size of the adipocytes were analyzed in wild-type and Slc10a6 −/− knockout mice. Soat expression was detected in mouse WAT, SAT, and BAT using immunofluorescence. The expression of Slc10a6 mRNA was significantly higher in 3T3-L1 adipocytes than that of preadipocytes and was significantly upregulated by exposure to lipopolysaccharide (LPS). Slc10a6 mRNA levels were also upregulated in the adipose tissue of LPS-treated mice. In Slc10a6 −/− knockout mice, adipocytes increased in size in the WAT and SAT of female mice and in the BAT of male mice, suggesting adipocyte hypertrophy. The serum levels of adiponectin, resistin, and leptin were comparable in wild-type and Slc10a6 −/− knockout mice. The treatment of 3T3-L1 adipocytes with DHEA significantly reduced lipid accumulation, while DHEAS did not have a significant effect. However, following LPS-induced Soat upregulation, DHEAS also significantly inhibited lipid accumulation in adipocytes. In conclusion, Soat-mediated import of DHEAS and other sulfated steroids could contribute to the complex pathways of sex steroid intracrinology in adipose tissues. Although in cell cultures the Soat-mediated uptake of DHEAS appears to reduce lipid accumulation, in Slc10a6 −/− knockout mice, the Soat deletion induced adipocyte hyperplasia through hitherto unknown mechanisms.

Adipose Tissue Compartments, Inflammation, and Cardiovascular Risk in the Context of Depression.

The neurobiological and behavioral underpinnings linking mental disorders, in particular, major depressive disorder (MDD), with cardiovascular disorders are a matter of debate. Recent research focuses on visceral (intra-abdominal and epicardial) adipose tissue and inflammation and their impact on the development of cardiometabolic disorders. Intra-abdominal adipose tissue is defined as an endocrine active fat compartment surrounding inner organs and is associated with type 2 diabetes mellitus, a risk factor for the later development of cardiovascular disorders. Epicardial (pericardial) adipose tissue is a fat compartment surrounding the heart with close proximity to the arteries supporting the heart. Visceral adipose tissue (VAT) is an important source of inflammatory mediators that, in concert with other risk factors, plays a leading role in cardiovascular diseases. In conjunction with the behavioral (physical inactivity, sedentary lifestyle), psychological (adherence problems), and hormonal (dysfunction of the hypothalamus–pituitary–adrenal axis with subsequent hypercortisolism) alterations frequently accompanying MDD, an enhanced risk for cardiovascular disorders results.

Intra-abdominal adipose depot variation in adipogenesis, lipogenesis, angiogenesis, and fibrosis gene expression and relationships with insulin resistance and inflammation in premenopausal women with severe obesity.

Although severe obesity is associated with insulin resistance (IR) and inflammation, secretory function of intra-abdominal adipose tissues and their relationships with IR and inflammation markers remain poorly understood. Aims were to measure gene expression of adipogenic (C/EBPα/β, PPARγ-1/2, SREBP-1c, LXRα), lipogenic (SCD1, DGAT-1/2), angiogenic (VEGFα, leptin), and fibrotic (LOX, COL6A3) factors in the round ligament (RL), omental (OM), and mesenteric (ME) fat depots and to evaluate their relationships with IR and inflammation markers in 48 women with severe obesity undergoing bariatric surgery. Gene expression was assessed by RT-qPCR, and plasma glucose and insulin (HOMA-IR calculated), PAI-1, IL-6, TNFα, adiponectin, and leptin levels were determined. C/EBPβ and PPARγ-1/2 mRNA levels were more expressed in the OM (0.001<p<0.05). ME showed the highest expression of C/EBPα, SREBP-1c, DGAT-2, and leptin and the lowest of SCD1, LXRα, VEGFα, and LOX (0.001<p<0.05). COL6A3 expression was higher in the ME and RL (p<0.001). COL6A3 expression was negatively associated with IR indices in the RL (0.01<p<0.05) and with fasting glycemia and HOMA-IR in the OM (0.001<p<0.05). VEGFα expression was positively related to TNFα and PAI-1 in the RL (0.001<p<0.05) and to PAI-1 in the OM (p<0.05) and negatively to PAI-1 in the ME (p<0.001). Fibrosis gene expression correlated negatively with inflammation in RL and OM (0.001<p<0.05) and positively with PAI-1 in the ME (0.001<p<0.05). The varying relationships of gene expression profiles with selected IR indices and inflammation biomarkers further suggest these fat depots have distinct contributions to overall health in premenopausal women with severe obesity.