Search

Aim: To examine the hypothesis that there would be ethnic differences in the relationship between ectopic fat and tissue‐specific insulin resistance (IR) across a spectrum of glucose tolerance in Black African (BA) and White European (WE) men. Materials and Methods: Fifty‐three WE men (23/10/20 normal glucose tolerance [NGT]/impaired glucose tolerance [IGT]/type 2 diabetes [T2D]) and 48 BA men (20/10/18, respectively) underwent a two‐step hyperinsulinaemic‐euglycaemic clamp with infusion of D‐[6,6‐2H2]‐glucose and [2H5]‐glycerol to assess hepatic, peripheral and adipose tissue IR. Magnetic resonance imaging was used to measure subcutaneous adipose tissue, visceral adipose tissue (VAT) and intrahepatic lipid (IHL). Associations between ectopic fat and IR were assessed using linear regression models. Results: There were no differences in tissue‐specific IR between ethnic groups at any stage of glucose tolerance. VAT level was consistently lower in the BA population; NGT (p = 0.013), IGT (p = 0.006) and T2D (p = 0.015). IHL was also lower in the BA compared with the WE men (p = 0.013). VAT and IHL levels were significantly associated with hepatic IR in the BA population (p = 0.001) and with peripheral IR in the WE population (p = 0.027). Conclusions: The present study suggests that BA and WE men exhibit the same degree of IR across a glucose tolerance continuum, but with lower VAT and IHL levels in the BA population, suggesting that IR may be driven by a mechanism other than increased ectopic fat accumulation in BA men. [ABSTRACT FROM AUTHOR]

Introduction Methods Results Conclusion In both highly industrialised and developing countries, obesity is reaching epidemic proportions and increasingly becoming a critical indicator of general morbidity, cardiovascular disease (CVD) and renal dysfunction. A promising trend in detection and management of obesity is the measurement of perirenal adipose tissue (PRAT), increasingly recognised as a metabolically active endocrine organ in itself. Its measurement by ultrasound is used increasingly to indicate visceral obesity and its clinical management. This review synthesises current techniques for measuring PRAT and its potential use as an indicator of CVD.We included clinical studies published between 2010 and 2023, investigating the current practice and use of specific ultrasonographic techniques and assessed the reliability and accuracy of included papers. The risk of bias was assessed using the Downs and Black Checklist, and the methodological quality examined using the Grade of Recommendations, Assessments, Development and Evaluation.It found, PRAT measures are predictive of CVD risk factors and the accuracy of ultrasound is comparable to CT and MRI, but there is no consistency in ultrasound technique. The lack of any randomised control trials and the use of 20 different non‐standardised ultrasound techniques across the 21 studies resulted in inconsistent and imprecise clinical observations and interpretations, which decreased the overall quality of the studies.This review found the inclusion of ultrasound measures in routine abdominal imaging potentially invaluable but demonstrates the need for standardisation of the perirenal fat ultrasound measuring technique to improve reproducibility and reliability. [ABSTRACT FROM AUTHOR]

Context Ectopic fat depots are related to the deregulation of energy homeostasis, leading to diseases related to obesity and metabolic syndrome (MetS). Despite significant changes in body composition over women's lifespans, little is known about the role of breast adipose tissue (BrAT) and its possible utilization as an ectopic fat depot in women of different menopausal statuses. Objective We aimed to assess the relationship between BrAT and metabolic glycemic and lipid profiles and body composition parameters in adult women. Methods In this cross-sectional study, we enrolled adult women undergoing routine mammograms and performed history and physical examination, body composition assessment, semi-automated assessment of breast adiposity (BA) from mammograms, and fasting blood collection for biochemical analysis. Correlations and multivariate regression analysis were used to examine associations of BA with metabolic and body composition parameters. Results Of the 101 participants included in the final analysis, 76.2% were in menopause, and 23.8% were in premenopause. The BA was positively related with fasting plasma glucose, glycated hemoglobin, homeostasis model assessment of insulin resistance, body mass index, waist circumference, body fat percentage, and abdominal visceral and subcutaneous fat when adjusted for age among women in postmenopause. Also, the BA was an independent predictor of hyperglycemia and MetS. These associations were not present among women in premenopause. Conclusion The BA was related to different adverse body composition and metabolic factors in women in postmenopause. The results suggest that there might be a relevant BrAT endocrine role during menopause, with mechanisms yet to be clarified, thus opening up research perspectives on the subject and potential clinical implications. [ABSTRACT FROM AUTHOR]

Obesity and sedentarism are associated with increased liver and pancreatic fat content (LFC and PFC, respectively) as well as impaired organ metabolism. Exercise training is known to decrease organ ectopic fat but its effects on organ metabolism are unclear. Genetic background affects susceptibility to obesity and the response to training. We studied the effects of regular exercise training on LFC, PFC, and metabolism in monozygotic twin pairs discordant for BMI. We recruited 12 BMI-discordant monozygotic twin pairs (age 40.4, SD 4.5 years; BMI 32.9, SD 7.6, 8 female pairs). Ten pairs completed six months of training intervention. We measured hepatic insulin-stimulated glucose uptake using [18F]FDG-PET and fat content using magnetic resonance spectroscopy before and after the intervention. At baseline LFC, PFC, gamma-glutamyl transferase (GT), and hepatic glucose uptake were significantly higher in the heavier twins compared to the leaner co-twins (p = 0.018, p = 0.02 and p = 0.01, respectively). Response to training in liver glucose uptake and GT differed between the twins (Time*group p = 0.04 and p = 0.004, respectively). Liver glucose uptake tended to decrease, and GT decreased only in the heavier twins (p = 0.032). In BMI-discordant twins, heavier twins showed higher LFC and PFC, which may underlie the observed increase in liver glucose uptake and GT. These alterations were mitigated by exercise. The small number of participants makes the results preliminary, and future research with a larger pool of participants is warranted. [ABSTRACT FROM AUTHOR]

This cardiometabolic imaging study was designed to document the adaptation of middle-aged recreational cyclists to a large exercise prescription not aiming at weight loss. Eleven middle-aged recreational male cyclists traveled 1,144 km over seven consecutive days. A comprehensive cardiometabolic profile including visceral and ectopic adiposity assessed by magnetic resonance imaging was obtained at baseline and following the exercise week. Cardiorespiratory fitness (CRF) was measured using maximal cardiopulmonary exercise testing. During the week, heart rate was monitored to calculate individual energy expenditure. Baseline characteristics of cyclists were compared with 86 healthy males in the same age range. Cyclists presented higher baseline CRF (+9.2 mL/kg/min, P < 0.0001) and lower subcutaneous (−56.2 mL, P < 0.05) and liver (−3.3%, P < 0.05) fat compared with the reference group. Despite the large energy expenditure during the cycling week, the increase in energy intake limited decreases in body weight (−0.8 ± 0.9 kg, P < 0.05) and body mass index (−0.3 ± 0.3 kg/m2, P < 0.05). Loss of fat mass (−1.5 ± 1.0 kg, P < 0.001) and a trend toward an increased lean mass (+0.8 ± 1.2 kg, P < 0.07) were observed. Visceral adiposity (−14.1 ± 14.2 mL, P < 0.01) and waist circumference (−3.2 ± 1.7 cm, P < 0.0001) decreased, whereas subcutaneous (−2.7 ± 5.1 mL, NS), liver (−0.5 ± 0.9%, NS), and cardiac (−0.3 ± 2.3 mL, NS) fat remained unchanged. This cardiometabolic imaging study documents middle-aged recreational cyclists' subcutaneous and visceral adiposity as well as cardiac and liver fat responses to a large volume of endurance exercise despite an increase in energy intake aimed at limiting weight loss. NEW & NOTEWORTHY: Even when being accompanied by a substantial increase in energy intake to compensate energy expenditure and limit weight loss, a large volume of endurance exercise performed within a short period of time is associated with a significant reduction in visceral adiposity. High cardiorespiratory fitness is associated with low levels of liver fat in middle-aged males. [ABSTRACT FROM AUTHOR]

Background/Objectives: The aim of the present study was to determine the effects of exercise training on ectopic and subcutaneous fat in patients with type 2 diabetes mellitus (T2DM). Methods: Web of Science, PubMed, and Scopus were searched for original articles published through November 2023 that included exercise versus control interventions on body mass (BM), liver fat percentage, visceral fat area (VFA), subcutaneous fat area (SFA), and intramuscular fat volume or mass (IMF) in patients with T2DM. Weighted mean differences (WMDs) for liver fat and BM, standardized mean differences (SMDs) for VFA, SFA, and IMF, and 95% confidence intervals (95% CIs) were determined using random-effects models. Results: Thirty-six studies comprising 2110 patients with T2DM were included in the present meta-analysis. Exercise training effectively reduced BM [WMD = −2.502 kg, p = 0.001], liver fat% [WMD = −1.559%, p = 0.030], VFA [SMD = −0.510, p = 0.001], and SFA [SMD = −0.413, p = 0.001] in comparison to the control. The IMF [SMD = 0.222, p = 0.118] remained unchanged compared to the controls. Subgroup analyses showed that the type of exercise, duration, and body mass index (BMI) of participants were sources of heterogeneity. Conclusions: The current meta-analysis provides strong evidence that exercise training, particularly aerobic and combined (aerobic and resistance) exercise programs, is effective for reducing BM, VFA, and SFA in patients with T2DM. However, aerobic exercise was more effective for reducing liver fat than combined exercise. The beneficial effects of exercise on VFA and SFA reduction, but not liver fat, are associated with weight loss. These findings highlight the importance of including consistent exercise as a key management component for T2DM and associated ectopic fat deposition, with potential long-term benefits for metabolic health. [ABSTRACT FROM AUTHOR]

Background The relationship between alcohol consumption and ectopic fat distribution, both known factors for cardiovascular disease, remains understudied. Therefore, we aimed to examine the association between alcohol consumption and ectopic adiposity in adults at risk for cardiovascular disease. Methods and Results In this cross-sectional analysis, we categorized alcohol intake among participants in MESA (Multi-Ethnic Study of Atherosclerosis) as follows (drinks/day): 2 (heavy drinking), former drinking, and lifetime abstention. Binge drinking was defined as consuming ≥5 drinks on 1 occasion in the past month. Visceral, subcutaneous, and intermuscular fat area, pericardial fat volume, and hepatic fat attenuation were measured using noncontrast computed tomography. Using multivariable linear regression, we examined the associations between categories of alcohol consumption and natural log-transformed fat in ectopic depots. We included 6756 MESA participants (62.1±10.2 years; 47.2% women), of whom 6734 and 1934 had chest computed tomography (pericardial and hepatic fat) and abdominal computed tomography (subcutaneous, intermuscular, and visceral fat), respectively. In adjusted analysis, heavy drinking, relative to lifetime abstention, was associated with a higher (relative percent difference) pericardial 15.1 [95% CI, 7.1-27.7], hepatic 3.4 [95% CI, 0.1-6.8], visceral 2.5 [95% CI, -10.4 to 17.2], and intermuscular 5.2 [95% CI, -6.6 to 18.4] fat but lower subcutaneous fat -3.5 [95% CI, -15.5 to 10.2]). The associations between alcohol consumption and ectopic adiposity exhibited a J-shaped pattern. Binge drinking, relative to light-to-moderate drinking, was also associated with higher ectopic fat. Conclusions Alcohol consumption had a J-shaped association with ectopic adiposity. Both heavy alcohol intake and binge alcohol drinking were associated with higher ectopic fat.

Ectopic fat accumulation in various organs and tissues, such as the liver, muscle, kidney, heart, and pancreas, is related to impaired capacity of adipose tissue to accumulate triglycerides, as a consequence of overnutrition and an unhealthy lifestyle. Ectopic fat promotes organ dysfunction and is a key factor in the development and progression of cardiometabolic diseases. Interest in intrapancreatic fat deposition (IPFD) has developed in the last few years, particularly in relation to improvement in methodological techniques for detection of fat in the pancreas, and to growing evidence for the role that IPFD might have in glucose metabolism disorders and cardiometabolic disease. Body weight reduction represents the main option for reducing fat, and the evidence consistently shows that hypocaloric diets are effective in reducing IPFD. Changes in diet composition, independently of changes in energy intake, might offer a more feasible and safe alternative treatment to energy restriction. This current narrative review focused particularly on the possible beneficial role of the diet and its nutrient content, in hypocaloric and isocaloric conditions, in reducing IPFD in individuals with high cardiometabolic risk, highlighting the possible effects of differences in calorie quantity and calorie quality. This review also describes plausible mechanisms by which the various dietary approaches could modulate IPFD. [ABSTRACT FROM AUTHOR]

Hepatic steatosis is known to be heritable, but its genetic basis is mostly uncharacterized. Steatosis is associated with metabolic and adiposity features; recent studies hypothesize that shared genetic effects between these traits could account for some of the unexplained heritability. This study aimed to quantify these genetic associations in a family-based sample of non-Hispanic white adults. 704 participants (18–95 years, 55.8% female) from the Fels Longitudinal Study with an MRI assessment of liver fat were included. Quantitative genetic analyses estimated the age- and sex-adjusted heritability of individual traits and the genetic correlations within trait pairs. Mean liver fat was 5.95% (SE = 0.23) and steatosis (liver fat >5.56%) was present in 29.8% of participants. Heritability (h2± SE) of steatosis was 0.72 ± 0.17 (p = 6.80e−6). All other traits including liver enzymes, fasting glucose, HOMA-IR, visceral and subcutaneous adipose tissue (VAT, SAT), body mass index, body fat percent, waist circumference, lipids and blood pressure were also heritable. Significant genetic correlations were found between liver fat and all traits except aspartate aminotransferase (AST), and among most trait pairs. Highest genetic correlations were between liver fat and HOMA-IR (0.85 ± 0.08, p = 1.73e−8), fasting glucose and ALT (0.89 ± 0.26, p = 6.68e−5), and HOMA-IR with: waist circumference (0.81 ± 0.12, p = 3.76e−6), body fat percent (0.78 ± 0.12 p = 2.42e−5) and VAT (0.73 ± 0.07, p = 6.37e−8). Common genes may exist between liver fat accumulation, metabolic features and adiposity phenotypes. • Steatosis and all other related phenotypes examined were significantly heritable. • Liver fat showed significant genetic correlation with various phenotypes. • The strongest genetic correlation of liver fat was with insulin resistance. • Glucose homeostasis phenotypes were also genetically correlated to adiposity traits. [ABSTRACT FROM AUTHOR]

This study aimed to compare fat accumulation in young and aged mice raised on a high-fat diet and to characterize the obesity-reducing effects of a Kampo medicine, bofutsushosan (BTS; fangfengtongshengsan in Chinese). Aged mice fed a high-fat diet containing 2% BTS extract for 28 days exhibited a significant reduction in weight gain and accumulation of visceral and subcutaneous fat, which were greater degree of reduction than those of the young mice. When the treatment period was extended to two months, the serum aspartate aminotransferase and alanine aminotransferase levels and the accumulation of fat droplets in the hepatocytes decreased. The mRNA expression of mitochondrial uncoupling protein 1 (UCP1) in the brown adipose tissue was significantly reduced in the aged mice compared to the young mice but increased by 2% in the BTS-treated aged mice. Additionally, the effect of BTS extract on oleic acid–albumin-induced triglyceride accumulation in hepatoblastoma-derived HepG2 cells was significantly inhibited in a concentration-dependent manner. Evaluation of the single crude drug extracts revealed that Forsythia Fruit, Schizonepeta Spike, and Rhubarb were the active components in BTS extract. These results suggest that BTS extract is effective against visceral, subcutaneous, and ectopic fats in the liver, which tend to accumulate with aging. Thus, BTS extract is useful in preventing and ameliorating the development of obesity and metabolic syndrome. [ABSTRACT FROM AUTHOR]

Resumen: Obesidad y diabetes mellitus tipo 2 (DM2) aumentan significativamente el riesgo de enfermedades cardiovasculares como enfermedad coronaria, fibrilación auricular, insuficiencia cardíaca y muerte súbita cardíaca. Este riesgo es proporcional al índice de masa corporal (IMC), se agrava con comorbilidades como la hipertensión y la dislipemia, e incluye factores de riesgo emergentes como la resistencia a la insulina, la inflamación crónica de bajo grado y la tendencia a la trombosis. La distribución del tejido adiposo, especialmente la grasa visceral y el depósito ectópico en el corazón, son otro factor clave en el desarrollo de enfermedades cardiovasculares en estos pacientes, junto con el remodelado auricular y ventricular. La cirugía bariátrica ha mostrado ser efectiva en reducir estos riesgos. La prevención y el tratamiento de las enfermedades cardiovasculares en obesidad y DM2 incluye cambios en el estilo de vida, tratamiento farmacológico específico y de las comorbilidades, y atención a los factores de riesgo cardiovascular. Abstract: Obesity and type 2 diabetes mellitus (T2D) significantly increase the risk of cardiovascular diseases such as coronary artery disease, atrial fibrillation, heart failure, and sudden cardiac death. This risk is proportional to body mass index (BMI), is exacerbated by comorbidities such as hypertension and dyslipidemia, and includes emerging risk factors like insulin resistance, low-grade chronic inflammation, and thrombosis tendency. The distribution of adipose tissue, especially visceral fat and ectopic deposition in the heart, is another key factor in the development of cardiovascular diseases in these patients, along with atrial and ventricular remodeling. Bariatric surgery has been shown to be effective in reducing these risks. The prevention and treatment of cardiovascular diseases in obesity and T2D include lifestyle changes, specific pharmacological treatment and management of comorbidities, and attention to cardiovascular risk factors.

The worldwide incidence of prediabetes/type 2 has continued to rise the last 40 years. In the same period, the mean daily energy intake has increased, and the quality of food has significantly changed. The chronic exposure of pancreatic β-cells to calorie excess (excessive energy intake) and food additives may increase pancreatic insulin secretion, decrease insulin pulses and/or reduce hepatic insulin clearance, thereby causing chronic hyperinsulinemia and peripheral insulin resistance. Chronic calorie excess and hyperinsulinemia may promote lipogenesis, inhibit lipolysis and increase lipid storage in adipocytes. In addition, calorie excess and hyperinsulinemia can induce insulin resistance and contribute to progressive and excessive ectopic fat accumulation in the liver and pancreas by the conversion of excess calories into fat. The personal fat threshold hypothesis proposes that in susceptible individuals, excessive ectopic fat accumulation may eventually lead to hepatic insulin receptor resistance, the loss of pancreatic insulin secretion, hyperglycemia and the development of frank type 2 diabetes. Thus, type 2 diabetes seems (partly) to be caused by hyperinsulinemia-induced excess ectopic fat accumulation in the liver and pancreas. Increasing evidence further shows that interventions (hypocaloric diet and/or bariatric surgery), which remove ectopic fat in the liver and pancreas by introducing a negative energy balance, can normalize insulin secretion and glucose tolerance and induce the sustained biochemical remission of type 2 diabetes. This pathophysiological insight may have major implications and may cause a paradigm shift in the management of type 2 diabetes: avoiding/reducing ectopic fat accumulation in the liver and pancreas may both be essential to prevent and cure type 2 diabetes. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the influence of vitamin D (VD) concentrations coupled with metabolic phenotypes preoperatively and 6 months after Roux-en-Y gastric bypass (RYGB) on body variables and weight loss. Materials and Methods: A longitudinal, retrospective, analytical study comprising 30 adult individuals assessed preoperatively (T0) and 6 months (T1) after undergoing Roux-en-Y gastric bypass. The participants were distributed preoperatively into metabolically healthy obese (MHO) and metabolically unhealthy obese individuals (MUHO) according to the HOMA-IR classification, as well as the adequacy and inadequacy of vitamin D concentrations in the form of 25(OH)D. All participants were assessed for weight, height, body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), visceral adiposity index (VAI), body circularity index (BCI), body adiposity index (BAI), weight loss, and assessment of 25(OH)D and 1,25(OH)2D concentrations using high-performance liquid chromatography with an ultraviolet detector (HPLC–UV). The statistical program used was SPSS version 21. Results: VD adequacy and a healthy phenotype in the preoperative period may play an important role concerning body fat distribution, as the body averages for WHtR (0.020*) and BCI (0.020*) were lower in MHO participants. In comparison, those with VD inadequacy and MUHOs had higher BAI averages (0.000*) in the postoperative period. Furthermore, it is possible that VD inadequacy before and after RYGB, even in the presence of an unhealthy phenotype, may contribute to the increase in VAI values (0.029*) after this surgery. Only those with inadequate VD and MUHOs had higher 25(OH)D concentrations. Besides, this unhealthy phenotype had a greater reduction in BMI in the early postoperative period (p < 0.001). Conclusion: This study suggests that VD adequacy and the presence of a healthy phenotype appear to have a positive impact on the reduction of visceral fat in the context of pre- and postoperative obesity. In addition, there was a greater weight reduction in those with VD inadequacy and in MUHO, which suggests that the volumetric dilution effect of VD and catabolism after bariatric surgery is more pronounced in this specific metabolic phenotype. [ABSTRACT FROM AUTHOR]

Introduction: The purpose of this study was to compare the difference in abdominal fat distribution between different metabolic groups and find the ectopic fat with the most risk significance. Methods: A total of 98 subjects were enrolled; there were 53 cases in the normal glucose metabolism group and 45 cases in the abnormal glucose metabolism group. Chemical shift-encoded magnetic resonance imaging was applied for quantification of pancreatic fat fraction (PFF) and hepatic fat fraction (HFF), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT). The correlation and the difference of fat distribution between different metabolism groups were analyzed. The receiver operating characteristic (ROC) curve was used to analyze the suggestive effect of different body fat fraction. Results: Correlation analysis showed that body mass index (BMI) had the strongest correlation with fasting insulin (r = 0.473, p < 0.001), HOMA-IR (r = 0.363, p < 0.001), and C-reactive protein (r = 0.245, p < 0.05). Pancreatic fat has a good correlation with fasting blood glucose (r = 0.247, p < 0.05) and HbA1c (r = 0.363, p < 0.001). With the increase of BMI, PFF, VAT, and SAT showed a clear upward trend, but liver fat was distributed relatively more randomly. The pancreatic fat content in the abnormal glucose metabolism group is significantly higher than that in the normal group, and pancreatic fat is also a reliable indicator of abnormal glucose metabolism, especially in the normal and overweight groups (the area under the curve was 0.859 and 0.864, respectively). Conclusion: MR-based fat quantification techniques can provide additional information on fat distribution. There are differences in fat distribution among people with different metabolic status. People with more severe pancreatic fat deposition have a higher risk of glucose metabolism disorders. [ABSTRACT FROM AUTHOR]

Abstract Background We aimed to explore the associations between thigh muscle fat density and vascular events. Methods A total of 3,595 adults (mean age, 57.2 years; women, 1,715 [47.7%]) without baseline cardiovascular events from the Korean Atherosclerosis Study-2 were included. Muscle and fat area at the mid-thigh level were measured by computed tomography (CT) using the following Hounsfield Unit range: 0–30 for low density muscle (LDM); 31–100 for normal density muscle (NDM); and − 250 to − 50 for fat. Results During a median follow-up period of 11.8 (4.3–13.9) years, vascular events occurred in 11.6% of men and 5.9% of women. Individuals with vascular events had a larger LDM area (men: 48.8 ± 15.5 cm2 vs. 44.6 ± 14.5 cm2; women: 39.4 ± 13.2 cm2 vs. 35.0 ± 11.8 cm2, both P < 0.001) compared with those who did not have vascular events during the follow-up of at least 5 years. The LDM/NDM ratio was also independently associated with vascular events after adjusting for cardiometabolic risk factors. Moreover, the LDM/NDM ratio improved the prognostic value for vascular events when added to conventional risk factors. Conclusions The current study suggests that a higher thigh muscle fat infiltration is associated with an increased risk of developing vascular events among Korean adults.

Introduction: The purpose of this study was to compare the difference in abdominal fat distribution between different metabolic groups and find the ectopic fat with the most risk significance. Methods: A total of 98 subjects were enrolled; there were 53 cases in the normal glucose metabolism group and 45 cases in the abnormal glucose metabolism group. Chemical shift-encoded magnetic resonance imaging was applied for quantification of pancreatic fat fraction (PFF) and hepatic fat fraction (HFF), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT). The correlation and the difference of fat distribution between different metabolism groups were analyzed. The receiver operating characteristic (ROC) curve was used to analyze the suggestive effect of different body fat fraction. Results: Correlation analysis showed that body mass index (BMI) had the strongest correlation with fasting insulin (r = 0.473, p < 0.001), HOMA-IR (r = 0.363, p < 0.001), and C-reactive protein (r = 0.245, p < 0.05). Pancreatic fat has a good correlation with fasting blood glucose (r = 0.247, p < 0.05) and HbA1c (r = 0.363, p < 0.001). With the increase of BMI, PFF, VAT, and SAT showed a clear upward trend, but liver fat was distributed relatively more randomly. The pancreatic fat content in the abnormal glucose metabolism group is significantly higher than that in the normal group, and pancreatic fat is also a reliable indicator of abnormal glucose metabolism, especially in the normal and overweight groups (the area under the curve was 0.859 and 0.864, respectively). Conclusion: MR-based fat quantification techniques can provide additional information on fat distribution. There are differences in fat distribution among people with different metabolic status. People with more severe pancreatic fat deposition have a higher risk of glucose metabolism disorders.

Background: We aimed to explore the associations between thigh muscle fat density and vascular events. Methods: A total of 3,595 adults (mean age, 57.2 years; women, 1,715 [47.7%]) without baseline cardiovascular events from the Korean Atherosclerosis Study-2 were included. Muscle and fat area at the mid-thigh level were measured by computed tomography (CT) using the following Hounsfield Unit range: 0–30 for low density muscle (LDM); 31–100 for normal density muscle (NDM); and − 250 to − 50 for fat. Results: During a median follow-up period of 11.8 (4.3–13.9) years, vascular events occurred in 11.6% of men and 5.9% of women. Individuals with vascular events had a larger LDM area (men: 48.8 ± 15.5 cm2 vs. 44.6 ± 14.5 cm2; women: 39.4 ± 13.2 cm2 vs. 35.0 ± 11.8 cm2, both P < 0.001) compared with those who did not have vascular events during the follow-up of at least 5 years. The LDM/NDM ratio was also independently associated with vascular events after adjusting for cardiometabolic risk factors. Moreover, the LDM/NDM ratio improved the prognostic value for vascular events when added to conventional risk factors. Conclusions: The current study suggests that a higher thigh muscle fat infiltration is associated with an increased risk of developing vascular events among Korean adults. [ABSTRACT FROM AUTHOR]

Obesity is a complex and multifactorial condition that poses significant health risks. Recent advancements in our understanding of obesity have highlighted the heterogeneity within this disorder. Identifying distinct subtypes of obesity is crucial for personalised treatment and intervention strategies. This review paper aims to examine studies that have utilised clinical biomarkers and genetic data to identify clusters or subtypes of obesity. The findings of these studies may provide valuable insights into the underlying mechanisms and potential targeted approaches for managing obesity‐related health issues such as type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: The accumulation of ectopic fats is related to metabolic syndromes with insulin resistance, which is considered as the first hit in obesity-related diseases. However, systematic understanding of the occurrence of ectopic fats is limited, since organisms are capable of orchestrating complicated intracellular signaling pathways to ensure that the correct nutritional components reach the tissues where they are needed. Interestingly, tissue-specific mechanisms lead to different consequences of fat metabolism with different insulin sensitivities. Aim of Review: To summarize the mechanisms of fat deposition in different tissues including adipose tissue, subcutis, liver, muscle and intestines, in an attempt to elucidate interactive mechanisms involving insulin actions and establish a potential reference for the rational uptake of fat. Key Scientific Concepts of Review: Tissue-specific fat metabolism serves as a trigger for developing abnormal fat metabolism or as a compensatory agent for regulating normal fat metabolism. Outcomes of de novo lipogenesis and adipogenesis differ in the subcutaneous adipose tissue (SAT), liver and muscle, with the participation of insulin actions. Overload of lipid metabolic capability results in SAT fat expansion, and ectopic fat accumulation implicates impaired lipo-/adipogenesis in SAT. Regulating insulin actions may be a key measure on fat deposition and metabolism in individuals.

Abstract Background Polycystic ovary syndrome (PCOS) is the most prevalent, chronic endocrine-metabolic disorder of adolescents and young women (AYAs), affecting 5–10% of AYAs worldwide. There is no approved pharmacological therapy for PCOS. Standard off-label treatment with oral contraceptives (OCs) reverts neither the underlying pathophysiology nor the associated co-morbidities. Pilot studies have generated new insights into the pathogenesis of PCOS, leading to the development of a new treatment consisting of a fixed, low-dose combination of two so-called insulin sensitisers [pioglitazone (PIO), metformin (MET)] and one mixed anti-androgen and anti-mineralocorticoid also acting as an activator of brown adipose tissue [spironolactone (SPI)], within a single tablet (SPIOMET). The present trial will evaluate the efficacy, tolerability and safety of SPIOMET, on top of lifestyle measures, for the treatment of PCOS in AYAs. Methods In this multicentre, randomised, double-blind, placebo-controlled, four-arm, parallel-group, phase II clinical trial, AYAs with PCOS will be recruited from 7 clinical centres across Europe. Intention is to randomise a total of 364 eligible patients into four arms (1:1:1:1): Placebo, PIO, SPI + PIO (SPIO) and SPI + PIO + MET (SPIOMET). Active treatment over 12 months will consist of lifestyle guidance plus the ingestion of one tablet daily (at dinner time); post-treatment follow-up will span 6 months. Primary endpoint is on- and post-treatment ovulation rate. Secondary endpoints are clinical features (hirsutism, menstrual regularity); endocrine-metabolic variables (androgens, lipids, insulin, inflammatory markers); epigenetic markers; imaging data (carotid intima-media thickness, body composition, abdominal fat partitioning, hepatic fat); safety profile; adherence, tolerability and acceptability of the medication; and quality of life in the study participants. Superiority (in this order) of SPIOMET, SPIO and PIO will be tested over placebo, and if present, subsequently the superiority of SPIOMET versus PIO, and if still present, finally versus SPIO. Discussion The present study will be the first to evaluate—in a randomised, double-blind, placebo-controlled way—the efficacy, tolerability and safety of SPIOMET treatment for early PCOS, on top of a lifestyle intervention. Trial registration EudraCT 2021–003177-58. Registered on 22 December 2021. https://www.clinicaltrialsregister.eu/ctr-search/search?query=%092021-003177-58 .

BackgroundWe have previously shown that the initiation of antiretroviral therapy (ART) is associated with a decrease in skeletal muscle density (greater fat accumulation), suggesting that gains in lean body mass seen in many ART studies may reflect gains in low quality, fatty muscle. Here, we explore whether skeletal muscle density and area are associated with markers of inflammation and immune activation.MethodsART-naïve people with HIV were randomized to raltegravir or ritonavir-boosted atazanavir or darunavir, each with tenofovir disoproxil fumarate/emtricitabine. Abdominal computed tomography scans from baseline and week 96 were reanalyzed for psoas density and area and correlations explored with inflammation [interleukin-6 (IL-6) and high-sensitivity C-reactive protein] and immune activation [soluble CD14 (sCD14), soluble CD163 (sCD163), and %CD38+HLADR+ on CD4+ or CD8+ T cells].ResultsTwo hundred twenty-two participants had available inflammation/immune activation markers and paired computed tomography scans. At baseline, lower psoas density (greater fat) correlated with higher IL-6 (r = -0.26, P < 0.001) and sCD163 (r -0.15, P = 0.03) and lower lean psoas area correlated with higher IL-6, high-sensitivity C-reactive protein, sCD14, sCD163, and %CD38+HLADR+ on CD4+ T cells (r = -0.30-0.13; all P ≤ 0.05). From baseline to week 96, greater percent decrease in total psoas density (more fat) correlated with greater increase in IL-6 (r = -0.14; P = 0.04); greater % decrease in lean psoas area correlated greater increases in IL-6, sCD14, sCD163, and %CD38+HLADR+ on CD8+ T cells (r = -0.15 to -0.18; all P < 0.04).ConclusionsGreater fat infiltration within the psoas muscle (lower density) and greater loss in lean psoas muscle area were associated with higher inflammation and immune activation, which may portend important effects on muscle function and cardiometabolic risk.

Obesity and sedentarism are associated with increased liver and pancreatic fat content (LFC and PFC, respectively) as well as impaired organ metabolism. Exercise training is known to decrease organ ectopic fat but its effects on organ metabolism are unclear. Genetic background affects susceptibility to obesity and the response to training. We studied the effects of regular exercise training on LFC, PFC, and metabolism in monozygotic twin pairs discordant for BMI. We recruited 12 BMI-discordant monozygotic twin pairs (age 40.4, SD 4.5 years; BMI 32.9, SD 7.6, 8 female pairs). Ten pairs completed six months of training intervention. We measured hepatic insulin-stimulated glucose uptake using [18F]FDG-PET and fat content using magnetic resonance spectroscopy before and after the intervention. At baseline LFC, PFC, gamma-glutamyl transferase (GT), and hepatic glucose uptake were significantly higher in the heavier twins compared to the leaner co-twins (p = 0.018, p = 0.02 and p = 0.01, respectively). Response to training in liver glucose uptake and GT differed between the twins (Time*group p = 0.04 and p = 0.004, respectively). Liver glucose uptake tended to decrease, and GT decreased only in the heavier twins (p = 0.032). In BMI-discordant twins, heavier twins showed higher LFC and PFC, which may underlie the observed increase in liver glucose uptake and GT. These alterations were mitigated by exercise. The small number of participants makes the results preliminary, and future research with a larger pool of participants is warranted.

Background: Polycystic ovary syndrome (PCOS) is the most prevalent, chronic endocrine-metabolic disorder of adolescents and young women (AYAs), affecting 5–10% of AYAs worldwide. There is no approved pharmacological therapy for PCOS. Standard off-label treatment with oral contraceptives (OCs) reverts neither the underlying pathophysiology nor the associated co-morbidities. Pilot studies have generated new insights into the pathogenesis of PCOS, leading to the development of a new treatment consisting of a fixed, low-dose combination of two so-called insulin sensitisers [pioglitazone (PIO), metformin (MET)] and one mixed anti-androgen and anti-mineralocorticoid also acting as an activator of brown adipose tissue [spironolactone (SPI)], within a single tablet (SPIOMET). The present trial will evaluate the efficacy, tolerability and safety of SPIOMET, on top of lifestyle measures, for the treatment of PCOS in AYAs. Methods: In this multicentre, randomised, double-blind, placebo-controlled, four-arm, parallel-group, phase II clinical trial, AYAs with PCOS will be recruited from 7 clinical centres across Europe. Intention is to randomise a total of 364 eligible patients into four arms (1:1:1:1): Placebo, PIO, SPI + PIO (SPIO) and SPI + PIO + MET (SPIOMET). Active treatment over 12 months will consist of lifestyle guidance plus the ingestion of one tablet daily (at dinner time); post-treatment follow-up will span 6 months. Primary endpoint is on- and post-treatment ovulation rate. Secondary endpoints are clinical features (hirsutism, menstrual regularity); endocrine-metabolic variables (androgens, lipids, insulin, inflammatory markers); epigenetic markers; imaging data (carotid intima-media thickness, body composition, abdominal fat partitioning, hepatic fat); safety profile; adherence, tolerability and acceptability of the medication; and quality of life in the study participants. Superiority (in this order) of SPIOMET, SPIO and PIO will be tested over placebo, and if present, subsequently the superiority of SPIOMET versus PIO, and if still present, finally versus SPIO. Discussion: The present study will be the first to evaluate—in a randomised, double-blind, placebo-controlled way—the efficacy, tolerability and safety of SPIOMET treatment for early PCOS, on top of a lifestyle intervention. Trial registration: EudraCT 2021–003177-58. Registered on 22 December 2021. https://www.clinicaltrialsregister.eu/ctr-search/search?query=%092021-003177-58. [ABSTRACT FROM AUTHOR]

AKT, serine/threonine protein kinase; AMPK, AMP-activated protein kinase; CD36, cluster of differentiation 36; CPT1, carnitine palmitoyltransferase-1; GLUTs, glucose transporters; GLUT4, glucose transporter 4; PGC-1α, PPARγ coactivator-1α; PTPN1 , protein tyrosine phosphatase nonreceptor type 1. [Display omitted] • Tissue-specific fat metabolism serves as a trigger for developing abnormal fat metabolism. • Tissue-specific fat metabolism is a compensatory agent for regulating normal fat metabolism. • Outcomes of de novo lipogenesis and adipogenesis differ in different tissues. • Insulin signaling pathways regulate lipo-/adipogenesis. • Regulating insulin actions may be a key measure on fat deposition and metabolism. The accumulation of ectopic fats is related to metabolic syndromes with insulin resistance, which is considered as the first hit in obesity-related diseases. However, systematic understanding of the occurrence of ectopic fats is limited, since organisms are capable of orchestrating complicated intracellular signaling pathways to ensure that the correct nutritional components reach the tissues where they are needed. Interestingly, tissue-specific mechanisms lead to different consequences of fat metabolism with different insulin sensitivities. To summarize the mechanisms of fat deposition in different tissues including adipose tissue, subcutis, liver, muscle and intestines, in an attempt to elucidate interactive mechanisms involving insulin actions and establish a potential reference for the rational uptake of fat. Tissue-specific fat metabolism serves as a trigger for developing abnormal fat metabolism or as a compensatory agent for regulating normal fat metabolism. Outcomes of de novo lipogenesis and adipogenesis differ in the subcutaneous adipose tissue (SAT), liver and muscle, with the participation of insulin actions. Overload of lipid metabolic capability results in SAT fat expansion, and ectopic fat accumulation implicates impaired lipo-/adipogenesis in SAT. Regulating insulin actions may be a key measure on fat deposition and metabolism in individuals. [ABSTRACT FROM AUTHOR]

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

Background: A "mismatch" sequence of less prenatal weight gain and more postnatal weight gain may lead to ectopic lipid accumulation, and trigger the development of early adrenarche/pubarche and the activation of the gonadotropic axis resulting in early puberty and ending up in full-blown adolescent polycystic ovary syndrome (PCOS). In the present study, we assess whether a low-dose combination of generics that collectively reduce ectopic fat through different pathways can slow down the accelerated maturation in "mismatch" girls with early puberty. Methods: Randomized, placebo-controlled, multicenter, phase 2a, study in 64 girls [age, 8.0–9.5 years; birthweight (BW) for gestational age: −2.5 < Z-score <0, body mass index (BMI): 0 < Z-score < +2.5 and early progressive puberty (Tanner B2 at 7.7–9.3 years)]. Pharmacological intervention will be with a half-dose version of SPIOMET (mini-spiomet), a combination that reverts the PCOS phenotype in "mismatch" adolescents; mini-spiomet will contain spironolactone (25 mg/day, to raise brown adipose tissue activity), pioglitazone (3.75 mg/day, to raise adiponectin and insulin sensitivity), and metformin (425 mg/day, to raise AMPK activity and GDF15). Recruitment: 1 year; double-blind treatment: 1 year; open follow-up: 1 year; analyses and reporting: 1 year. Interventions: randomization (1:1) for placebo vs mini-spiomet. Primary outcome: annualized bone age advancement (0–1 year) by BoneXpert; secondary outcomes: insulin, IGF-I, high-molecular-weight adiponectin (HMW-adip), sex hormone binding globulin (SHBG), ultra-sensitive C-reactive protein (usCRP), androgens, luteinizing hormone (LH), follicle-stimulating hormone (FSH), oestradiol, growth-and-differentiation factor 15 (GDF15), C-X-C motif chemokine ligand-14 (CXCL14), safety parameters, and quantification of hepato-visceral fat. Discussion: The present study, if successful, may provide a first proof of the concept that the rapid maturation of girls with an upward mismatch between pre- and post-natal weight gain can be slowed down with a fixed low-dose combination of old and safe generics jointly targeting a reduction of ectopic fat without necessarily lowering body weight. Trial registration: EudraCT 2021-006766-21. Registered on May 30, 2022. [ABSTRACT FROM AUTHOR]

Abstract Background Ectopic fat is fat that accumulates in or around specific organs or compartments of the body including myocardium. The clinical features of type 2 diabetes patients with high fat accumulation in the myocardium remain unknown. Moreover, little is known about the influence of myocardial fat accumulation in type 2 diabetes on coronary artery disease and cardiac dysfunction. We aimed to clarify the clinical features, including cardiac functions, of type 2 diabetes patients with myocardial fat accumulation. Methods We retrospectively enrolled type 2 diabetes patients who underwent ECG-gated coronary computed tomography angiography (CCTA) and abdominal computed tomography (CT) scan examinations within 1 year of CCTA from January 2000 to March 2021. High fat accumulation in the myocardium was defined as the low mean myocardial CT value of three regions of interest, and the associations between CT values and clinical characteristics or cardiac functions were assessed. Results In total, 124 patients were enrolled (72 males and 52 females). The mean age was 66.6 years, the mean BMI was 26.2 kg/m2, the mean ejection fraction (EF) was 67.6%, and the mean myocardial CT value was 47.7 Hounsfield unit. A significant positive correlation was found between myocardial CT value and EF (r = 0.3644, p = 0.0004). The multiple regression analyses also showed that myocardial CT value was independently associated with EF (estimate, 0.304; 95% confidence interval (CI) 0.092 to 0.517; p = 0.0056). Myocardial CT value showed significant negative correlations with BMI, visceral fat area and subcutaneous fat area (r = − 0.1923, − 0.2654, and -0.3569, respectively, p

Background The relationship between alcohol consumption and ectopic fat distribution, both known factors for cardiovascular disease, remains understudied. Therefore, we aimed to examine the association between alcohol consumption and ectopic adiposity in adults at risk for cardiovascular disease. Methods and Results In this cross‐sectional analysis, we categorized alcohol intake among participants in MESA (Multi‐Ethnic Study of Atherosclerosis) as follows (drinks/day): 2 (heavy drinking), former drinking, and lifetime abstention. Binge drinking was defined as consuming ≥5 drinks on 1 occasion in the past month. Visceral, subcutaneous, and intermuscular fat area, pericardial fat volume, and hepatic fat attenuation were measured using noncontrast computed tomography. Using multivariable linear regression, we examined the associations between categories of alcohol consumption and natural log‐transformed fat in ectopic depots. We included 6756 MESA participants (62.1±10.2 years; 47.2% women), of whom 6734 and 1934 had chest computed tomography (pericardial and hepatic fat) and abdominal computed tomography (subcutaneous, intermuscular, and visceral fat), respectively. In adjusted analysis, heavy drinking, relative to lifetime abstention, was associated with a higher (relative percent difference) pericardial 15.1 [95% CI, 7.1–27.7], hepatic 3.4 [95% CI, 0.1–6.8], visceral 2.5 [95% CI, −10.4 to 17.2], and intermuscular 5.2 [95% CI, −6.6 to 18.4] fat but lower subcutaneous fat −3.5 [95% CI, −15.5 to 10.2]). The associations between alcohol consumption and ectopic adiposity exhibited a J‐shaped pattern. Binge drinking, relative to light‐to‐moderate drinking, was also associated with higher ectopic fat. Conclusions Alcohol consumption had a J‐shaped association with ectopic adiposity. Both heavy alcohol intake and binge alcohol drinking were associated with higher ectopic fat.

Aims: The excess deposition of intra-pancreatic fat deposition (IPFD) has been reported to be associated with type 2 diabetes, chronic pancreatitis, and pancreatic ductal adenocarcinoma. In the current study, we aimed to identify a relationship between lifestyle factors and IPFD. Materials and methods: 99 patients admitted to the Osaka University Hospital who had undergone abdominal computed tomography were selected. We evaluated the mean computed tomography values of the pancreas and spleen and then calculated IPFD score. Multiple regression analyses were used to assess the associations between IPFD score and lifestyle factors. Results: Fast eating speed, late-night eating, and early morning awakening were significantly associated with a high IPFD score after adjusting for age, sex, diabetes status and Body Mass Index (p=0.04, 0.01, 0.01, respectively). Conclusion: The current study has elucidated the significant associations of fast eating speed, late-night eating, and early morning awakening with IPFD. [ABSTRACT FROM AUTHOR]

A short-term high-calorie high-fat diet (HCHFD) impairs insulin sensitivity in non-obese South Asian but not Caucasian men; however, the effect of short-term HCHFD on insulin sensitivity in East Asians is unknown. We recruited 21 healthy non-obese Japanese men to evaluate metabolic parameters and gut microbiota before and after 6-day HCHFD consisting of a regular diet plus a 45% energy excess with dairy fat supplementation. We evaluated tissue-specific insulin sensitivity and metabolic clearance rate of insulin (MCRI) using a two-step hyperinsulinemic euglycemic clamp, glucose tolerance using the glucose tolerance test, and measured ectopic fat in muscle and the liver using ¹H-magnetic resonance spectroscopy. The primary outcome of this study was insulin sensitivity measured by the clamp study. The secondary/exploratory outcomes were other metabolic changes. After HCHFD, levels of circulating lipopolysaccharide binding protein (LBP), a marker of endotoxemia, increased by 14%. In addition, intramyocellular lipid levels in the tibialis anterior and soleus and intrahepatic lipid levels increased by 47%, 31%, and 200%, respectively. Insulin sensitivity decreased by 4% in muscle and 8% in liver. However, even with reduced insulin sensitivity, glucose metabolism was maintained by increased serum insulin concentrations due to lower MCRI and higher endogenous insulin secretion during the clamp. Glucose levels during the meal tolerance test were comparable before and after HCHFD. In conclusion, short-term HCHFD impaired insulin sensitivity in the muscle and livers of non-obese Japanese men with increased LBP and ectopic fat accumulation. Elevated insulin levels from modulated insulin secretion and clearance might contribute to the maintenance of normal glucose metabolism during the clamp and meal tolerance test. [ABSTRACT FROM AUTHOR]

Abstract Background A “mismatch” sequence of less prenatal weight gain and more postnatal weight gain may lead to ectopic lipid accumulation, and trigger the development of early adrenarche/pubarche and the activation of the gonadotropic axis resulting in early puberty and ending up in full-blown adolescent polycystic ovary syndrome (PCOS). In the present study, we assess whether a low-dose combination of generics that collectively reduce ectopic fat through different pathways can slow down the accelerated maturation in “mismatch” girls with early puberty. Methods Randomized, placebo-controlled, multicenter, phase 2a, study in 64 girls [age, 8.0–9.5 years; birthweight (BW) for gestational age: −2.5 < Z-score

Abstract Objective Ectopic fat deposition within and around organs is a stronger predictor of cardiometabolic disease status than body mass index (BMI). Fat deposition within the lymphatic system is poorly understood. This study examined the association between the prevalence of cardiometabolic disease and ectopic fat deposition within axillary lymph nodes (LNs) visualized on screening mammograms. Methods A cross‐sectional study was conducted on 834 women presenting for full‐field digital screening mammography. The status of fat‐infiltrated LNs was assessed based on the size and morphology of axillary LNs from screening mammograms. The prevalence of cardiometabolic disease was retrieved from the electronic medical records, including type 2 diabetes mellitus (T2DM), hypertension, dyslipidemia, high blood glucose, cardiovascular disease, stroke, and non‐alcoholic fatty liver disease. Results Fat‐infiltrated axillary LNs were associated with a high prevalence of T2DM among all women (adjusted odds ratio: 3.92, 95% CI: [2.40, 6.60], p‐value < 0.001) and in subgroups of women with and without obesity. Utilizing the status of fatty LNs improved the classification of T2DM status in addition to age and BMI (1.4% improvement in the area under the receiver operating characteristic curve). Conclusion Fat‐infiltrated axillary LNs visualized on screening mammograms were associated with the prevalence of T2DM. If further validated, fat‐infiltrated axillary LNs may represent a novel imaging biomarker of T2DM in women undergoing screening mammography.

Adolescent polycystic ovary syndrome (PCOS) has long been thought to be a gynecological disorder. However, emerging evidence suggests that it is not a disorder but a reversible, endocrine mode in response to ectopic fat. A simple way of screening for ectopic fat is to verify whether there has been an upward percentile crossing from weight at birth to body mass index (BMI) in adolescence. Adolescent PCOS has so far been viewed as a disorder starting post menarche. The present view is that adolescent PCOS can only be understood by looking backward into early life: relatively high concentrations of circulating luteinizing hormone (LH), thyroid-stimulating hormone (TSH), free T3, testosterone, dehydroepiandrosterone sulfate (DHEAS), and/or fasting insulin are reminiscent of a childhood wherein the same adaptive responses to ectopic fat enabled girls to accelerate their growth and maturation (with early pubarche/puberty/menarche) to outgrow their ectopic fatness and generate evolutionary fitness. The definition of adolescent PCOS continues to be a matter of debate. We propose to merge the latest definitions of adolescent PCOS into a single set of diagnostic criteria. Traditional treatment of adolescent PCOS focuses on symptoms. There is now evidence that treatment should also target ectopic fat and ultimately aim for preconception health. Adolescent polycystic ovary syndrome (PCOS) is a highly prevalent, reversible, endocrine-metabolic mode essentially driven by ectopic fat, which, in turn, often results from a mismatch between early adipogenesis and later lipogenesis, or between prenatal and postnatal weight gain. The key features of adolescent PCOS are menstrual irregularity and androgen excess (hirsutism, acne, and/or high testosterone). Adolescent PCOS is frequently preceded by rapid maturation (early variants of adrenarche/pubarche and puberty/menarche, also accelerated by ectopic fat) and is diagnosed between 2 and 8 years after menarche, thus during late adolescence or early adulthood. Treatment of adolescent PCOS should not only focus on symptoms, but also reduce the amount of ectopic fat, thereby aiming for an overall state of preconception health. [ABSTRACT FROM AUTHOR]

Background: Ectopic fat is fat that accumulates in or around specific organs or compartments of the body including myocardium. The clinical features of type 2 diabetes patients with high fat accumulation in the myocardium remain unknown. Moreover, little is known about the influence of myocardial fat accumulation in type 2 diabetes on coronary artery disease and cardiac dysfunction. We aimed to clarify the clinical features, including cardiac functions, of type 2 diabetes patients with myocardial fat accumulation. Methods: We retrospectively enrolled type 2 diabetes patients who underwent ECG-gated coronary computed tomography angiography (CCTA) and abdominal computed tomography (CT) scan examinations within 1 year of CCTA from January 2000 to March 2021. High fat accumulation in the myocardium was defined as the low mean myocardial CT value of three regions of interest, and the associations between CT values and clinical characteristics or cardiac functions were assessed. Results: In total, 124 patients were enrolled (72 males and 52 females). The mean age was 66.6 years, the mean BMI was 26.2 kg/m2, the mean ejection fraction (EF) was 67.6%, and the mean myocardial CT value was 47.7 Hounsfield unit. A significant positive correlation was found between myocardial CT value and EF (r = 0.3644, p = 0.0004). The multiple regression analyses also showed that myocardial CT value was independently associated with EF (estimate, 0.304; 95% confidence interval (CI) 0.092 to 0.517; p = 0.0056). Myocardial CT value showed significant negative correlations with BMI, visceral fat area and subcutaneous fat area (r = − 0.1923, − 0.2654, and -0.3569, respectively, p < 0.05). In patients who were ≥ 65 years or female, myocardial CT value showed significant positive correlations with not only EF (r = 0.3542 and 0.4085, respectively, p < 0.01) but also early lateral annular tissue Doppler velocity (Lat e') (r = 0.5148 and 0.5361, respectively, p < 0.05). The multiple regression analyses showed that myocardial CT value was independently associated with EF and Lat e' in these subgroups (p < 0.05). Conclusions: Patients with type 2 diabetes, especially in elderly or female patients, who had more myocardial fat had more severe left ventricular systolic and diastolic dysfunctions. Reducing myocardial fat accumulation may be a therapeutic target for type 2 diabetes patients. [ABSTRACT FROM AUTHOR]

Aim: To assess the efficacy and safety of liraglutide to reduce visceral and ectopic fat in adults with or without type 2 diabetes mellitus (T2DM). Methods: Four databases were searched up to 6 May 2022 for randomized clinical trials assessing the effect of liraglutide on visceral and ectopic fat. The mean and standard deviation of the values of visceral fat, ectopic fat and body mass index were calculated. Subgroup analyses were performed based on the type of disease (T2DM or non‐T2DM), duration of intervention, dosage of liraglutide and whether life interventions were added to liraglutide therapy. We extracted and integrated the safety assessments reported in each article. Results: Sixteen randomized clinical trials with, in total, 845 participants were included in the meta‐analysis. Liraglutide could significantly decrease visceral fat [standard mean difference (SMD) = −0.72, 95% confidence interval (CI; −1.12, −0.33)], liver fat [SMD = −0.78, 95% CI (−1.24, −0.32)] and body mass index [weighted mean difference = −1.44, 95% CI (−1.95, −0.92)] in adult patients with or without T2DM when compared with the control group. However, reduction of epicardial fat by liraglutide [SMD = −0.74, 95% CI (−1.82, 0.34)] was not statistically significant. Subgroup analysis revealed that an adequate dosage (≥1.8 mg/day) and appropriate duration of treatment (ranging from 16 to 40 weeks) were the decisive factors for liraglutide to reduce visceral fat effectively. Mild gastrointestinal reactions were the main adverse event of liraglutide. Conclusions: Liraglutide significantly and safely reduces visceral and ectopic liver fat irrespective of T2DM status, and reduces visceral fat provided adequate dosage and duration of therapy are ensured. [ABSTRACT FROM AUTHOR]

AimsThe excess deposition of intra-pancreatic fat deposition (IPFD) has been reported to be associated with type 2 diabetes, chronic pancreatitis, and pancreatic ductal adenocarcinoma. In the current study, we aimed to identify a relationship between lifestyle factors and IPFD.Materials and methods99 patients admitted to the Osaka University Hospital who had undergone abdominal computed tomography were selected. We evaluated the mean computed tomography values of the pancreas and spleen and then calculated IPFD score. Multiple regression analyses were used to assess the associations between IPFD score and lifestyle factors.ResultsFast eating speed, late-night eating, and early morning awakening were significantly associated with a high IPFD score after adjusting for age, sex, diabetes status and Body Mass Index (p=0.04, 0.01, 0.01, respectively).ConclusionThe current study has elucidated the significant associations of fast eating speed, late-night eating, and early morning awakening with IPFD.

Objective: Obesity is a significant risk factor for adverse outcomes following coronavirus infection (COVID-19). However, BMI fails to capture differences in the body fat distribution, the critical driver of metabolic health. Conventional statistical methodologies lack functionality to investigate the causality between fat distribution and disease outcomes.Methods: We applied Bayesian network (BN) modelling to explore the mechanistic link between body fat deposition and hospitalisation risk in 459 participants with COVID-19 (395 non-hospitalised and 64 hospitalised). MRI-derived measures of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and liver fat were included. Conditional probability queries were performed to estimate the probability of hospitalisation after fixing the value of specific network variables.Results: The probability of hospitalisation was 18% higher in people living with obesity than those with normal weight, with elevated VAT being the primary determinant of obesity-related risk. Across all BMI categories, elevated VAT and liver fat (>10%) were associated with a 39% mean increase in the probability of hospitalisation. Among those with normal weight, reducing liver fat content from >10% to

Background: Renal 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. Methods: Participants 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. Results: No 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. Conclusions: Differential 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.

Over the past decades, adapted lifestyle and dietary habits in industrialized countries have led to a progress of obesity and associated metabolic disorders. Concomitant insulin resistance and derangements in lipid metabolism foster the deposition of excess lipids in organs and tissues with limited capacity of physiologic lipid storage. In organs pivotal for systemic metabolic homeostasis, this ectopic lipid content disturbs metabolic action, thereby promotes the progression of metabolic disease, and inherits a risk for cardiometabolic complications. Pituitary hormone syndromes are commonly associated with metabolic diseases. However, the impact on subcutaneous, visceral, and ectopic fat stores between disorders and their underlying hormonal axes is rather different, and the underlying pathophysiological pathways remain largely unknown. Pituitary disorders might influence ectopic lipid deposition indirectly by modulating lipid metabolism and insulin sensitivity, but also directly by organ specific hormonal effects on energy metabolism. In this review, we aim to I) provide information about the impact of pituitary disorders on ectopic fat stores, II) and to present upto-date knowledge on potential pathophysiological mechanisms of hormone action in ectopic lipid metabolism. [ABSTRACT FROM AUTHOR]

Effective nutrition therapy is a pressing issue in obesity and type 2 diabetes mellitus (T2DM) management. As such, this research aimed to determine the performance of a revised dietary strategy built on the protein-sparing diet in obesity and type 2 diabetes mellitus with regard to obtaining a rapid and stable improvement in glucometabolic control, body weight, body composition, and energy metabolism when applying the strategy in just twenty-one days. The revised protein-sparing diet differs from the traditional protein-sparing modified fast (PSMF) because it does not include foods. The daily calorie intake of this diet is exclusively derived from Isolate whey protein in addition to a formulation of Isolate whey protein enriched with essential amino acids in free form, with the addition of lipids such as extra virgin olive oil and coconut oil as a source of medium chain fatty acids, where the latter is taken for only the first four days of the diet, together with the use, for the same duration, of extended-release metformin, as the only antihyperglycemic allowed. Anthropometric measurements, bioimpedance analysis, indirect calorimetry, and blood chemistry assessments were conducted at the beginning of the study, time 0 (T0), and at the end, time 1 (T1), i.e., on the 21st day. The main outcomes of the revised protein-sparing diet after only twenty-one days were a reduction in body weight with the predominant loss of visceral atherogenic abdominal fat and, therefore, a possible contextual reduction in ectopic fat deposits together with a simultaneous reduction in insulin resistance and normalization of insulin levels, maintenance of free fat mass and basal metabolism, restoration of metabolic flexibility, and improvement of the glucometabolic and lipidic parameters. These results demonstrate the promising potential of the revised protein-sparing diet as an "etiologic tool" in the integrated nutritional treatment of metabolic diseases such as obesity and type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Objective: Ectopic fat deposition within and around organs is a stronger predictor of cardiometabolic disease status than body mass index (BMI). Fat deposition within the lymphatic system is poorly understood. This study examined the association between the prevalence of cardiometabolic disease and ectopic fat deposition within axillary lymph nodes (LNs) visualized on screening mammograms. Methods: A cross‐sectional study was conducted on 834 women presenting for full‐field digital screening mammography. The status of fat‐infiltrated LNs was assessed based on the size and morphology of axillary LNs from screening mammograms. The prevalence of cardiometabolic disease was retrieved from the electronic medical records, including type 2 diabetes mellitus (T2DM), hypertension, dyslipidemia, high blood glucose, cardiovascular disease, stroke, and non‐alcoholic fatty liver disease. Results: Fat‐infiltrated axillary LNs were associated with a high prevalence of T2DM among all women (adjusted odds ratio: 3.92, 95% CI: [2.40, 6.60], p‐value < 0.001) and in subgroups of women with and without obesity. Utilizing the status of fatty LNs improved the classification of T2DM status in addition to age and BMI (1.4% improvement in the area under the receiver operating characteristic curve). Conclusion: Fat‐infiltrated axillary LNs visualized on screening mammograms were associated with the prevalence of T2DM. If further validated, fat‐infiltrated axillary LNs may represent a novel imaging biomarker of T2DM in women undergoing screening mammography. [ABSTRACT FROM AUTHOR]

Over the past decades, adapted lifestyle and dietary habits in industrialized countries have led to a progress of obesity and associated metabolic disorders. Concomitant insulin resistance and derangements in lipid metabolism foster the deposition of excess lipids in organs and tissues with limited capacity of physiologic lipid storage. In organs pivotal for systemic metabolic homeostasis, this ectopic lipid content disturbs metabolic action, thereby promotes the progression of metabolic disease, and inherits a risk for cardiometabolic complications. Pituitary hormone syndromes are commonly associated with metabolic diseases. However, the impact on subcutaneous, visceral, and ectopic fat stores between disorders and their underlying hormonal axes is rather different, and the underlying pathophysiological pathways remain largely unknown. Pituitary disorders might influence ectopic lipid deposition indirectly by modulating lipid metabolism and insulin sensitivity, but also directly by organ specific hormonal effects on energy metabolism. In this review, we aim to I) provide information about the impact of pituitary disorders on ectopic fat stores, II) and to present up-to-date knowledge on potential pathophysiological mechanisms of hormone action in ectopic lipid metabolism.

Background Larger epicardial fat volume (EFV) has been associated with increased risks of cardiovascular disease and atrial fibrillation. Yet, evidence on the association of EFV with cardiac function and incident heart failure (HF) remains scarce. Methods and Results We included 2103 participants (mean age, 68 years; 54.4% women) from the prospective population‐based RS (Rotterdam Study) with computed tomography–based EFV and repeated echocardiography‐based assessment of left ventricular (LV) systolic and diastolic function. Linear mixed effects and Cox‐proportional hazard regression models, adjusted for cardiovascular risk factors, were used to assess the associations of EFV with repeated measurements of echocardiographic parameters and with incident HF. During a median follow‐up of 9.7 years, 124 HF events occurred (incidence rate, 6.37 per 1000 person‐years). For LV systolic function, 1‐SD larger EFV was associated with 0.76 (95% CI, 0.54–0.98) mm larger LV end‐diastolic dimension, 0.66 (95% CI, 0.47–0.85) mm larger LV end‐systolic dimension, and 0.56% (95% CI, −0.86% to −0.27%) lower LV ejection fraction. Interactions between EFV and time were small. For LV diastolic function, 1‐SD larger EFV was associated with 1.02 (95% CI, 0.78–1.27) mm larger left atrial diameter. Larger EFV was also associated with incident HF (hazard ratio per 1‐SD increase in EFV, 1.34 [95% CI, 1.07–1.68] per 1‐SD larger EFV). Conclusions We report an independent association between EFV with new‐onset HF in the general population. EFV seems to exert its influence on HF through different pathways contributing to deteriorations in systolic function and larger left atrial size in part, likely through mechanical restraint and hypertrophy.

BackgroundType 2 resistant starch (RS2) has been shown to improve glycemic control and some cardiovascular endpoints in rodent and human studies.ObjectiveThe aim of this study was to perform one of the first randomized clinical trials in adults with prediabetes and one of the longest trials to test whether RS2 can improve cardiometabolic health.Design68 overweight [body mass index (BMI) ≥27 kg/m2] adults aged 35-75 y with prediabetes were randomized to consume 45 g/d of high-amylose maize (RS2) or an isocaloric amount of the rapidly digestible starch amylopectin (control) for 12 wk. At baseline and postintervention, ectopic fat depots (visceral adipose tissue, intrahepatic lipids, and intramyocellular lipids) were measured by magnetic resonance imaging/spectroscopy, energy metabolism by respiratory chamber, and carbohydrate metabolism by glycated hemoglobin (HbA1c), an intravenous glucose tolerance test, and a meal tolerance test. Cardiovascular risk factors-serum lipids, blood pressure, heart rate, and inflammatory markers (high-sensitivity C-reactive protein [hs-CRP], interleukin-6, and tumor necrosis factor [TNF]-α)-were also measured. The primary endpoints were insulin sensitivity, insulin secretion, ectopic fat, and markers of inflammation. Data were primarily analyzed as treatment effects via a linear mixed model both with and without the addition of covariates.ResultsRelative to the control group, RS2 lowered HbA1c by a clinically insignificant 0.1 ± 0.2% (Δ = -1 ± 2 mmol/mol; P = 0.05) but did not affect insulin secretion, insulin sensitivity, the disposition index, or glucose or insulin areas under the curve relative to baseline (P ≥ 0.23). RS2 decreased heart rate by 5 ± 9 beats/min (P = 0.02) and TNF-α concentrations by 2.1 ± 2.7 pg/mL (P = 0.004), relative to the control group. Ectopic fat, energy expenditure, substrate oxidation, and all other cardiovascular risk factors were unaffected (P ≥ 0.06).Conclusions12 wk of supplementation with resistant starch reduced the inflammatory marker TNF-α and heart rate, but it did not significantly improve glycemic control and other cardiovascular disease risk factors, in adults with prediabetes. This trial was registered at clinicaltrials.gov as NCT01708694.