A spoonful of sugar makes the liver grow fat

Ectopic fat storage occurs when fats are stored in places other than subcutaneous adipose tissue, which is where most fat is stored under healthy conditions, or in the visceral fat. In fact, the Greek roots for the word “ectopic” literally mean “out of place.” Common ectopic sites include the liver, pancreas, skeletal muscle, and the heart. The root cause of ectopic fat deposition is unknown, but, as laid out in Figure 1, it is thought to occur^[1] when adipose tissue has an impaired ability to store additional fat through decreased expandability. When triglycerides are redirected and stored in organs such as the liver or skeletal muscle, where very little fat is typically stored, it can lead to an impairment of normal organ function and is associated with disorders such as insulin resistance^[2] and type 2 diabetes^[3].

A systematic review^[4] concluded that a hypercaloric diet with excessive sugars can increase ectopic fat deposits, particularly in the liver and skeletal muscle. Because of this, several overfeeding studies have been conducted in order to examine how excessive nutrition impacts ectopic fat storage, insulin resistance, and other aspects of metabolism such as energy expenditure. One such study^[5] compared the effects of overfeeding with either glucose or fructose in healthy men. The hypercaloric diet the participants were given amounted to about 35% additional calories on top of a weight maintenance diet. The researchers found that both sugars increased liver fat storage and fasting triglyceride levels, while only overfeeding with glucose led to increase fat storage in skeletal muscle tissue.

There is also a suggestion that a high protein intake might mitigate the increases in liver fat or muscle fat deposition caused by overfeeding. In one study^[6], participants were fed either a hypercaloric high fat or high fat and high protein diet for four days. The diet containing the high protein levels was able to significantly reduce the increase in liver fat, compared to the lower protein, high fat diet.

However, ectopic fat storage comparisons of sucrose overfeeding with diets consisting of different fat and protein concentrations have not been performed in humans. The closest study so far has been a sucrose overfeeding study in rats^[7] given diets of varying fat and protein concentrations, which also resulted in a blunting effect of protein with respect to increased fat deposition. The study under review is the first such study to compare sucrose overfeeding between diets differing in fat and protein levels, and how that impacts ectopic fat storage in humans.

Ectopic fat deposition, which can be promoted by hypercaloric diets, has been linked to organ malfunction and corresponding disorders such as insulin resistance and diabetes. Overfeeding studies have shown that protein may help reduce the levels of ectopic fat deposition. However, overfeeding studies using sucrose while also varying the protein content of the experimental diets have only been performed in rodents. The study under review is the first to examine the macronutrient interactions in humans.