When it comes to how fat affects metabolic risk factors, the issue is where, not how much and the latest hot spot is the liver.
According to Samuel Klein, M.D., of Washington University School of Medicine in St. Louis, Missouri, several studies have shown that visceral fat is associated with increased risk of factors leading to diabetes and heart disease.
But the real culprit is fat in the liver: other visceral fat might just be an “innocent bystander,” Klein’s group reported online in the Proceedings of the National Academy of Sciences. In a cohort study, they found that obese people with the same visceral fat volume, but different levels of liver fat, had important variations in markers of metabolic disorders.
On the other hand, there were no differences among people with different fat volumes but the same level of liver fat, they found. “We have found that excess fat in the liver, not visceral fat, is a key marker of metabolic dysfunction,” Klein said in a statement.
For the study, 20 volunteers were matched for their volume of adipose tissue, but had either a normal or high level of liver fat. Normal was defined as no more than 5.5% of liver content, while high was more than 10%.
Another 20 were matched for liver fat levels but differed in visceral adipose tissue volume. Some volunteers were assigned to more than one group. The researchers used stable isotope tracer techniques and the euglycemic-hyperinsulinemic clamp procedure to measure insulin sensitivity and the very-low density lipoprotein-triglyceride (VLDL-TG) secretion rate.
Adipose tissue volume was measured by magnetic resonance imaging and dual-energy x-ray absorptiometry.
- No differences in insulin sensitivity or the VLDL-TG secretion rate among volunteers matched for liver fat content, regardless of the volume of adipose tissue
- In participants matched for fat volume, higher than normal liver fat resulted in hepatic, adipose tissue and muscle insulin sensitivity that was 41%, 13%, and 36% lower, respectively, than among those with normal liver fat. The differences were all significant at P<0.01.
- At the same time, the VLD-TG secretion rate in people with higher than normal liver fat was almost double that seen in those with normal livers. The rate was 23 micromoles per minute in the high-fat volunteers, compared with 12 in the normal-fat participants (P<0.001).
The researchers also found significant differences in the levels of CD36, a cell membrane protein involved in the uptake of plasma free fatty acids.
Among those with higher than normal liver fat, CD36 expression was lower in adipose tissue and higher in skeletal muscle than among those with normal liver fat (with both differences significant at P<0.05).
That pattern, Klein and colleagues said, implies greater uptake of plasma free fatty acids in muscle — and presumably liver — tissue.
The bottom line, they argued, is that the observed link between fat volume and the metabolic abnormalities associated with obesity arises because visceral adipose tissue and liver fat levels are often correlated.
Fabbrinia E, et al “Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity” PNAS 2009; DOI: 10.1073/pnas.0904944106.