Visceral Adipose Tissue (VAT)

Visceral Adipose Tissue (VAT)

Subcutaneous fat is the adipose (fat) tissue just under the skin that can be pinched and felt. Visceral adipose tissue (VAT) is belly fat deeper in the abdominal cavity that wraps around the internal organs. VAT is independently associated with cardiovascular disease (CVD), type 2 diabetes (T2D), Metabolic Syndrome, and multiple cancers. The association for these conditions is stronger for VAT than it is for subcutaneous fat, body mass index (BMI), or total fat mass and evidence increasingly supports VAT being a direct cause of these conditions. VAT is metabolically active tissue that creates a pro-inflammatory, insulin resistant state by releasing free fatty acids, dysregulated adipokines, and inflammatory cytokines.(1,2,3)

Cardiovascular Disease

There is a strong, dose-dependent association between VAT and CVD. In the Mutli-Ethnic Study of Atherosclerosis, 1,910 individuals with CT measured VAT showed that VAT, but not subcutaneous fat, was significantly associated with CVD risk regardless of age, sex, race, or ethnicity.(4) In the Framingham cohorts, each standard deviation increase in CT-quantified VAT was associated with about a 40% higher risk of subsequent CVD.(5) The American Heart Association (AHA) scientific statement concludes that at any BMI, individuals with excess VAT represent the subgroup at the highest CVD risk, and that VAT “serves as a clear health hazard”.(1)

Type 2 Diabetes and Metabolic Syndrome

Increased VAT is associated with increased risk of T2D, insulin resistance, and atherogenic dyslipidemia regardless of BMI (7,9), an association not seen with gluteofemoral (hip and thigh) fat or subcutaneous fat, demonstrating that fat distribution more than total fat is the main driver of risk.(10) Studies quantifying VAT using DXA (7,8) suggest VAT ≥ 100 cm2 is predictive of Metabolic Syndrome, T2D, and insulin resistance.(8) Waist circumference and waist-to-height ratio were similarly predictive as DXA (8) and does not require specialized equipment or radiation exposure, making it a good proxy for assessing VAT and associated risks.

Cancer

Increased VAT is associated with increased risk of getting, and dying from, obesity-related cancers. (11,12,13) Each additional 100 cm2 of VAT corresponds to a 32% higher risk of obesity-related cancers, with a nearly two-fold increase in the highest quartile. (11) Mendelian randomization supports a causal effect of VAT with pancreatic cancer and lung squamous-cell carcinoma. (14) An integrative review concluded that VAT increases the risk of colorectal, pancreatic, and gastro-esophageal cancers, with sex- and menopause-specific effects for breast, endometrial, and renal cancers. (15)

Mechanism

The underlying driver of disease risk with regards to VAT is through chronic low-grade inflammation (“metainflammation”) with macrophage infiltration and elevated inflammatory markers (TNF-ɑ, IL-6), reduced adiponectin and altered adipokine secretion, increased free-fatty-acids promoting insulin resistance and fat deposition, insulin resistance resulting in hyperinsulinemia and IGF-1 axis stimulation (relevant to cancer), and endothelial dysfunction/oxidized LDL formation promoting atherosclerosis (relevant to heart disease). (2,3,7,9,16)

Interventions to Reduce VAT

Exercise, calorie restriction, GLP-1 receptor agonists, SGLT2 inhibitors, and bariatric surgery all reduce VAT and translate to improved cardiometabolic outcomes through improved insulin sensitivity, glycemic control, lipids, and inflammatory markers. (17,18,19)

Exercise

Aerobic exercise is the most consistently effective lifestyle modality for VAT reduction. (18,20) Aerobic exercise reduces VAT even without weight loss, and relative to the weight lost, exercise removes more VAT than diet or pharmacotherapy. (1,19) The AHA notes that aerobic interventions are the most beneficial and meeting 150 min/week of activity may be sufficient to reduce VAT (1) but aerobic exercise shows a dose-dependent effect, where more aerobic exercise translates to greater loss. (18,20)

Caloric Restriction

Hypocaloric diets are effective at reducing VAT (21) as well as improving glucose tolerance and insulin sensitivity. (22) Combining exercise with a hypocaloric diet is generally recommended for the most sustainable cardiometabolic benefit. (19)

GLP-1 receptor agonists (GLP-1 RAs)

GLP-1 RAs preferentially reduce VAT and also improve glycemic and cardiovascular risk. A meta-analysis of 10 randomized controlled trials (RCTs) in T2D found GLP-1 RAs preferentially reduced VAT (~11.2%) versus subcutaneous fat (~8.3%) (23) while also reducing liver fat content, (24) improving liver enzymes (24) and reducing major adverse cardiac events (MACE). (9,25)

SGLT2 inhibitors

SGLT2 inhibitors reduce VAT, epicardial (around the heart), and intrahepatic (within the liver) fat and are superior to GLP-1 RAs in reducing epicardial adipose tissue (26) making them the drug of choice in people with T2D and heart or kidney disease. (9)

Bariatric Surgery

Surgery produces the largest sustained reductions in VAT and ectopic fat. (19,27) This is accompanied by cardiometabolic improvements in markers of insulin sensitivity (HOMA-IR, HbA1c), lipid profile (HDL), and inflammatory markers ( IL-6, CRP). (28)

Conclusion

Excess VAT is associated with several disease outcomes and is a health hazard. Pharmacotherapy and surgery reduce VAT more than exercise but exercise removes the most VAT relative to total weight loss. Combining a hypocaloric diet and exercise with pharmacotherapy or surgery yields the greatest and most long-lasting cardiometabolic benefit.

Disclaimer: this article is for educational purposes only, is not medical advice, and does not create a patient-physician relationship.

References:

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