Role of visceral adipose tissue in aging

Abstract

Background: Visceral fat (VF) accretion is a hallmark of aging in humans. Epidemiologic studies have implicated abdominal obesity as a major risk factor for insulin resistance, type 2 diabetes, cardiovascular disease, metabolic syndrome and death.

Methods: Studies utilizing novel rodent models of visceral obesity and surgical strategies in humans have been undertaken to determine if subcutaneous (SC) abdominal or VF are causally linked to age-related diseases.

Results: Specific depletion or expansion of the VF depot using genetic or surgical tools in rodents has been shown to have direct effects on disease risk. In contrast, surgically removing large quantities of SC fat does not consistently improve metabolic parameters in humans or rodents, while benefits were observed with SC fat expansion in mice, suggesting that SC fat accrual is not an important contributor to metabolic decline. There is also compelling evidence in humans that abdominal obesity is a stronger risk factor for mortality risk than general obesity. Likewise, we have shown that surgical removal of VF improves mean and maximum lifespan in rats, providing the first causal evidence that VF depletion may be an important underlying cause of improved lifespan with caloric restriction.

General significance: This review provides both corollary and causal evidence for the importance of accounting for body fat distribution, and specifically VF, when assessing disease and mortality risk. Given the hazards of VF accumulation on health, treatment strategies aimed at selectively depleting VF should be considered as a viable tool to effectively reduce disease risk in humans.

Figure 1

Survival curve of the three groups of rats (AL-fed, dashed line; VF-removed, dotted line; and CR, solid line). CR rats had the greatest mean and maximum lifespan but VF removal only was sufficient to extend lifespan as compared to AL controls and accounted for nearly 20% of the CR effect on lifespan. Figure is from Muzumdar et al. [82] and is presented with permission from Aging Cell.

Figure 2

The proposed link among VF, age-related diseases and lifespan. The accumulation of VF, which is a hallmark of aging, is hypothesized to pose a greater risk for the development of insulin resistance and other features of the metabolic syndrome than other fat depots due to its anatomical location, high lipolytic rate and secretion of inflammatory adipokines. Some specific perturbations to tissues by increased VF include hepatic insulin resistance, impaired glucose uptake by skeletal muscle and increased basal lipolytic rate and FFA release by adipose tissue. The long-term consequence of VF-induced metabolic decline includes enhanced risk for several age-related diseases such as CVD, T2DM, Alzheimer’s disease and certain cancers. Therefore, VF accretion would be expected to increase mortality risk and reduce lifespan.