Visceral and ectopic fat, atherosclerosis, and cardiometabolic disease: a position statement

The prevalence of obesity in the United States and the world has risen to epidemic/pandemic proportions. This increase has occurred despite great efforts by healthcare providers and consumers alike to improve the health-related behaviors of the population and a tremendous push from the scientific community to better understand the pathophysiology of obesity. This epidemic is all the more concerning given the clear association between excess adiposity and adverse health consequences such as cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). The risks associated with overweight/obesity are primarily related to the deposition of adipose tissue, which leads to excess adiposity or body fatness. Furthermore, weight loss, specifically loss of body fat, is associated with improvement in obesity-related comorbidities. Before weight loss interventions can be recommended, however, patients must be assessed for their adiposity-related risk. Unfortunately, healthcare providers and systems have not done a good job of assessing for excess adiposity even in its simplest form, such as measuring body mass index (BMI). It is for these reasons that we must emphasize the importance of assessing adiposity in clinical practices. Although it can be argued that the entire population should be targeted as an important public health issue with a goal of prevention of weight gain and obesity, there are currently so many “at risk” individuals that simple strategies to identify and treat those individuals are necessary. We must identify those individuals at highest risk of comorbidities in order to identify those who might benefit the most from aggressive weight management. This scientific statement will first briefly review the epidemiology of obesity and its related comorbidities, supporting the need for improved assessment of adiposity in daily clinical practice. This will be followed by a discussion of some of the challenges and issues associated with assessing adiposity and then by a review …

The regional distribution of adipose tissue (AT) is a major determinant of metabolic and cardiovascular diseases. The mass of fat in the visceral area associates independently of obesity with the development and progression of cardiovascular diseases in a series of clinical and epidemiological studies.1 This led to the concept of a pathophysiological link between abdominal obesity and metabolic syndrome. More recently, fat depots localized around the heart, highly variable among individuals, were proposed to contribute to the pathogenesis of coronaropathy independently of other visceral depots (ie, in the omental and mesenteric area).2,3 The study by Greif et al3a in this issue of Arteriosclerosis, Thrombosis, and Vascular Biology highlights the association between pericardial adipose tissue (PAT) and the number of atherosclerotic plaques evaluated concomitantly by Dual source CT scan. This measurement was qualitatively interpretable in 264 consecutive patients with a large range of age, a normal or moderately increased body mass index (BMI), and no a priori coronary disease. An estimated volume of pericardial fat more than 300 cm3 provided an incremental value for the presence of coronary atherosclerosis (odds ratio 4.1) independently of well known risk factors (hyperglycemia or diabetes, hypercholesterolemia, hypertension, and smoking). Ninety-five percent of patients with PAT volume >300 cm3 had one or more atherosclerotic plaques by ROC estimation. In univariate statistical analysis, PAT …

the physiological roles of human epicardial adipose tissue (EAT) are not well defined because this strategically located white adipose tissue (WAT) depot is difficult to access and study, and most of the information about it comes from humans with severe cardiac diseases undergoing open heart

To assess the efficacy and safety of liraglutide to reduce visceral and ectopic fat in adults with or without type 2 diabetes mellitus (T2DM). 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. 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 (≥1.8mg/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. 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.

This study investigates the clinical significance of ectopic fat and iron deposition in the liver and pancreas for glucose metabolism in elderly obese patients, with a focus on their potential for early diabetes screening and intervention. We conducted a cross-sectional study of 140 elderly obese patients (aged 65-80 years, BMI ≥28 kg/m²) who underwent MRI quantification of hepatic and pancreatic fat (MRI-PDFF) and iron content (R2* values), along with measurements of visceral and subcutaneous fat via T2-weighted imaging. Glucose metabolism was assessed through oral glucose tolerance testing and related biomarkers. Compared to normal glucose tolerance (NGT) and impaired glucose regulation (IGR) groups, elderly obese patients with type 2 diabetes mellitus (T2DM) showed significantly higher ectopic fat in the liver (16.6% vs 6.9-13.4%) and pancreas (13.5% vs 8.5-9.0%), as well as increased visceral fat area (198.0cm² vs 137.8-163.9cm²). Liver fat percentage >11.8% was identified as an independent risk factor for abnormal glucose metabolism (OR=2.05, 95% CI 1.22-3.14), with a 2.05-fold increased risk compared to lower levels. The optimal diagnostic thresholds were determined as 11.8% for liver fat (sensitivity 83.2%, specificity 56.1%; AUC = 0.823) and 6.9% for pancreatic fat (sensitivity 72.2%, specificity 50.2%; AUC = 0.688), highlighting their clinical utility for early risk stratification. Ectopic fat deposition in the liver, particularly when exceeding 11.8%, is a significant independent risk factor for glucose metabolism abnormalities in elderly obese patients. Our findings demonstrate that MRI-based quantification of hepatic fat provides a valuable tool for early identification of diabetes risk, enabling targeted interventions to prevent disease progression. This study highlights the clinical importance of monitoring ectopic fat deposition in clinical practice for elderly obese populations.

Visceral and ectopic fat accumulation might have an impact on the atherosclerotic calcification of abdominal arteries. The pattern of calcification of the abdominal aorta and its branches is not fully investigated. We retrospectively analyzed the abdominopelvic MSCT images and calculated calcification volumes of the abdominal aorta, celiac trunk, superior and inferior mesenteric arteries, and both common and external iliac arteries. On the same MSCT scans, a visceral fat volume and ectopic fat deposits (liver-to-spleen ratio (L/S) and pancreas-to-spleen (P/S) ratio) were also measured. The results showed that calcifications of the abdominal aorta and its branches were associated with visceral fat volume, less strongly associated with L/S, and not associated with the P/S ratio. The abdominal aorta, the common iliac and external iliac arteries were more calcified arteries compared to the celiac trunk and superior and mesenterial arteries. In conclusion, visceral fat has a stronger effect on abdominopelvic arteries' calcification than ectopic fat. Visceral aortic branches are generally less calcified than iliac arteries.

This Month in Gastroenterology

The role of ectopic fat, insulin secretion and clearance in the preservation ofβ-cell function in black African women with obesity who typically present with hyperinsulinaemia is not clear. We aim to examine the associations between disposition index (DI, an estimate of β-cell function), insulin secretion and clearance and ectopic fat deposition. This is a cross-sectional study of 43 black South African women (age 20–35 years) with obesity (BMI 30–40 kg/m2) and without type 2 diabetes that measured the following: DI, insulin sensitivity (SI), acute insulin response (AIRg), insulin secretion rate (ISR), hepatic insulin extraction and peripheral insulin clearance (frequently sampled i.v. glucose tolerance test); pancreatic and hepatic fat, visceral adipose tissue (VAT) and abdominal s.c. adipose tissue (aSAT) volume (MRI), intra-myocellular (IMCL) and extra-myocellular fat content (EMCL) (magnetic resonance spectroscopy). DI correlated positively with peripheral insulin clearance (β 55.80, P = 0.002). Higher DI was associated with lower VAT, pancreatic fat and soleus fat, but VAT explained most of the variance in DI (32%). Additionally, higher first phase ISR (P = 0.033) and lower hepatic insulin extraction (P = 0.022) were associated with lower VAT, independent from SI, rather than with ectopic fat. In conclusion, peripheral insulin clearance emerged as an important correlate of DI. However, VAT was the main determinant of a lower DI above ectopic fat depots. Importantly, VAT, but not ectopic fat, is associated with both lower insulin secretion and higher hepatic insulin extraction. Prevention of VAT accumulation in young black African women should, therefore, be an important target for beta cell preservation.

Visceral Adipose Tissue Attacks Beyond the Liver: Esophagogastric Junction as a New Target

With obesity assuming pandemic proportion, cardiometabolic diseases are also increasing across the globe. Obesity defined as excess and dysfunctional adipose tissue that is detrimental to health, is very heterogeneous with many subtypes based on the distribution of body fat. These subtypes vary in their risk of cardiometabolic diseases. The adipose tissue comprises of visceral adipose tissue (VAT) and subcutaneous adipose tissue, which differ not only in their anatomical location but also in their cellular composition, molecular structure, physiological function, and pathological consequences. VAT is a metabolically active component with several physiological functions and pathophysiological links to cardiometabolic diseases. VAT has unique adipocytes with various paracrine and endocrine functions. It not only stores lipids but also contributes significantly to energy homeostasis. Sexual dimorphism in relation to VAT and cardiometabolic health has been described. VAT is metabolically active, with higher insulin resistance and increased sensitivity to lipolysis. Excess accumulation of VAT termed visceral obesity, leads to the secretion of adipocytokines, ectopic fat storage, and an alteration in the immune landscape of the VAT, resulting in the clustering of the cardiometabolic risk factors. Visceral obesity is correlated with cardiometabolic diseases and higher mortality. Many epidemiological studies have shown the link between visceral adiposity and cardiometabolic diseases such as diabetes, hypertension, dyslipidemia, cerebrovascular disease, heart failure, and unexpected cardiac death. Obesity phenotypes describing body composition and adipose density distribution are better at defining the cardiometabolic risk profile. Several imaging modalities with advancements in technology, such as dual-energy X-ray absorptiometry, computed tomography, MRI, and Bioimpedance, have explored the link between visceral fat and cardiometabolic risk. Calorie restriction, structured exercise, pharmacotherapy, and metabolic surgeries have shown beneficial effects in reducing VAT. Preferential VAT loss has been shown to have a favorable effect on cardiometabolic diseases.

Adipose tissue is a recognized endocrine organ that acts not only as a fuel storage but also is able to secrete adipokines that can modulate inflammation. Most of the fat is composed of white adipocytes (WAT), although also brown/beige adipocytes (BAT/BeAT) have been found in humans. BAT is located close to the neck but also among WAT in the epicardial fat and perivascular fat. Adipocyte hypertrophy and infiltration of macrophages impair adipose tissue metabolism determining "adiposopathy" (i.e., sick fat) and increasing the risk to develop metabolic and cardiovascular diseases. The purpose of this review was to search and discuss the available literature on the impact of different types of fat and fat distribution on cardiometabolic risk. Visceral fat, but also ectopic fat, either in liver, muscle and heart, can increase the risk to develop insulin resistance, type 2 diabetes and cardiovascular diseases. Results recently published showed that BAT could have an impact on cardiometabolic risk, not only because it is implicated in energy metabolism but also because it can modulate glucose and lipid metabolism. Therapeutical interventions that can increase energy expenditure, successfully change fat distribution and reduce ectopic fat, also through BAT activation, were discussed.

The Effects of Dietary Soybean Oil on Liver Fat and Visceral Adipose Tissue in Adults With Nonalcoholic Fatty Liver Disease: Study Protocol for a Randomized Control Trial

Implications of Elevated Serum Alanine Aminotransferase Levels: Think Outside the Liver

Introduction: Patients with coronary artery diseases (CAD) are often characterized by impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or type 2 diabetes (T2D), conditions which have also been related to high levels of visceral adipose tissue (VAT) and ectopic fat. Secondary prevention intervention involving physical activity should therefore also target VAT/ectopic fat to improve the cardiometabolic risk (CMR) profile. Objectives: The objective of the present pilot study was to compare the response of CMR variables in recent post coronary bypass graft patients with either normal glucose tolerance (NGT), IFG/IGT, and T2D to a 1-year intervention targeting the improvement of lifestyle habits. Methods: Anthropometric measurements, assessment of lipid profile, magnetic resonance imaging of the heart and the abdomen, an oral glucose tolerance test and a maximal exercise treadmill test were performed before and after the intervention (n=44). Results: No significant difference was found in baseline characteristics of the three subgroups, except that patients with IFG/IGT and T2D had significant higher levels of VAT than NGT patients. In response to the lifestyle intervention, patients with IFG/IGT and T2D improved their CMR profile with decreases in waist circumference (Δ=-5.1cm, p<0.01), abdominal visceral (Δ=-41.1ml/5mm, p<0.01) and subcutaneous adipose tissue volumes (Δ=-32.7ml/5mm, p<0.01) as well as in their intrathoracic epicardial (Δ=-3.5ml/5mm, p<0.0001) and pericardial (Δ=-7.7ml/5mm p<0.0001) adipose tissue volumes. They also improved their lipid/lipoprotein profile with decreases in apolipoproteins B (Δ=-0.02mmol/l, p<0.05), triglycerides (Δ=-0.17mmol/l, p<0.01) and total cholesterol/HDL ratio (Δ=-0.49mmol/l, p<0.0001), while HDL (Δ=+0.20mmol/l, p<0.01) and apolipoproteins A1 (Δ=+0.12mmol/l, p<0.01) increased. Cardiorespiratory fitness (CRF) was also improved as reflected by an increase in VO2peak (Δ=+5.06 mlO2/kg/min, p<0.0001) and by a reduced heart rate assessed at a standardized workload (1.7 mph, 5% slope) (Δ=-10bpm, p<0.0001). Patients with IFG/IG also improved significantly their glucose and insulin homeostasis with decreases in fasting glucose (Δ=-0.12mmol/l, p<0.05) and insulin levels (Δ=-15.53mmol/l, p<0.05), 2h-glucose (Δ=-1.50mmol/l, p<0.01) and insulin levels (Δ=-40.41mmol/l, p<0.05) and glucose area under the curve (Δ=-0.17 ρmolx10-3, p<0.01). Nine of seventeen patients with IFG/IGT normalized their glucose tolerance and two of nine patients with T2D reversed to IGT/IFG. Improvements of CMR variables were significantly correlated with changes in CRF. Conclusion: Results of this pilot study suggest that increasing CRF is a relevant target to mobilize VAT/ectopic fat in order to improve the CMR profile including plasma glucose homeostasis in CAD patients, irrespective of their glucose tolerance status.

Bariatric surgery induces a fast loss of weight and a remission duration of metabolic diseases, but the distribution of fat loss in the regions that causes such changes is still not adequately described. The magnetic resonance imaging (MRI) technique allows the accurate quantification of the location of abdominal fat and ectopic fat deposits. Objective: To analyze dynamic changes in abdominal fat distribution during rapid weight loss after bariatric surgery using MRI and to evaluate their association with metabolic improvement.Methodology: It was a prospective longitudinal research that involved 72 patients who have bariatric surgery between June 2024 and June 2025 at Jinnah Hospital, Lahore. Premoperative and post-operative recorded anthropometric parameters and laboratory investigations of metabolism. The baseline, 3 months and 6 months of postoperative were used to conduct MRI in order to quantify visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), hepatic fat fraction, and pancreatic fat fraction. Repeated-measures ANOVA and Pearson correlation tests were used to test the statistical significance.Results: Significant reductions were observed in body weight, BMI, and waist circumference at all follow-up intervals (p<0.001). MRI demonstrated a marked decline in visceral fat compared with subcutaneous fat, resulting in a decreased VAT/SAT ratio. Hepatic and pancreatic fat fractions also showed substantial reduction. Decrease in visceral fat strongly correlated with improvement in HbA1c and fasting glucose, while reduction in liver fat correlated with triglyceride improvement. Conclusion: Rapid metabolic recovery after bariatric surgery is primarily driven by preferential reduction of visceral and ectopic fat rather than total weight loss alone. MRI-based fat quantification serves as a valuable tool for assessing metabolic response following bariatric procedures.