Respective Roles of Visceral Fat and Liver Fat

The portal theory links fatty liver to visceral fat [1]. Visceral fat is known to be both highly metabolically active [2] and to be drained by the portal vein [1], which connects to the liver. The portal theory suggests that high rates of lipolysis from the large visceral adipose depot cause excess free fatty acid (FFA) flux to the liver via the portal vein. This in turn leads to hepatic insulin resistance, triglyceride accumulation in the hepatocytes, and increased synthesis and secretion of atherogenic lipoproteins (see Liver Fat) (Figure 1). Supporting this theory is evidence of a moderate association between amount of visceral fat and degree of liver fat deposition [3-5]. Recent evidence also suggests that a high-fat diet increases lipid turnover from the visceral fat depot (due to enhanced gene expression of major regulators of FFA release). This may affect gene expression at the liver, causing more fat to be stored in hepatic tissue [6] and decreasing hepatic insulin clearance [7]. Further, it has been argued that the central nervous system may play a key role in the development of cardiometabolic risk and may link visceral adiposity to dysregulation of hepatic function [8]. Accordingly, it has been proposed that in a high-fat fed state, the adrenergic nervous system induces rhythmic lipolysis of visceral fat (which peaks during sleep), exposing the liver to excess FFA on an ongoing basis and possibly contributing to hepatic insulin resistance [8].

While some argue in favour of the portal theory or a link between visceral fat and liver fat [9], additional findings have failed to support this theory [10,11]. In addition, as scientific testing of the portal theory would require in vivo sampling of the portal vein, a difficult procedure, direct evidence supporting this hypothesis is hard to come by [12]. Moreover, new techniques have shown that of the FFA delivered to the liver via the portal vein, only approximately 5 to 20% of these come from visceral adipose tissue, with the remainder coming from the much larger subcutaneous fat depot [13]. The relationship between visceral fat and liver fat therefore remains largely theoretical and debatable [12].

Although fatty liver is commonly associated with obesity [14], excess visceral fat in particular [3-5], many researchers have found that liver fat and metabolic complications are strongly linked, independent of total and abdominal obesity [4,5,11,15]. However, while both visceral fat and liver fat are clearly related to metabolic risk factors [5,16], exactly how these two fat depots are independently related to metabolic risk is difficult to detangle, and further evidence is needed. For example, several studies have reported that liver fat content is linked to metabolic risk independent of visceral adiposity in obese women with previous gestational diabetes [10], overweight non-diabetic men [11], and men with type 2 diabetes [17]. Conversely, other studies have reported that both visceral fat and liver fat independently predict certain metabolic risk factors [3,5]. However, in both studies the amount of visceral fat was the strongest predictor of metabolic abnormalities [3,5]. The amount of visceral adipose tissue, and not liver fat, has also been linked to selected metabolic risk factors in lean premenopausal women [18] and to all-cause mortality in a sample of men [19].

The degree of fat infiltration of the liver and the amount of visceral fat both seem to independently contribute to metabolic risk. While liver fat and visceral fat are clearly related, it has not yet been determined whether this relationship is causal or merely correlative. It is plausible that liver fat and visceral fat may simply be two depots for storing excess energy that develop independent of one another and increase metabolic risk via related or unrelated mechanisms (Figure 2).