Published: Oct 7, 2013 | Updated: Oct 7, 2013

By Kristina Fiore

Full Story:  http://www.medpagetoday.com/Endocrinology/Obesity/42105

The amount of fat that accumulates in the liver may be a key mediator of metabolically healthy obesity, researchers found.

In a twin study involving pairs in which one twin was obese and the other thin, the pairs that had similar levels of liver fat had equally healthy metabolic profiles, according to Kirsi Pietilainen, MD, of the University of Helsinki in Finland, and colleagues.

But among pairs in which the obese twin had more liver fat, metabolic profiles diverged, and obese twins had more insulin resistance, dyslipidemia, and more inflammation, the researchers reported online in Diabetologia.

The findings make it clear that “metabolic responses to obesity differ vastly,” Pietilainen and colleagues wrote. “Half of the obese co-twins exhibited a typical response to obesity, with marked insulin resistance, dyslipidemia, and fatty liver, whereas the other half were metabolically as healthy as their lean co-twins.”

It’s well known that not all obese patients have the metabolic problems that are associated with obesity. The exact mechanisms aren’t clear, but some work has suggested that metabolically healthier obese patients have less visceral adipose tissue, and less ectopic fat deposition in the liver and skeletal muscle than insulin-resistant obese patients.

Other studies have also suggested that fatty liver plays a role in metabolically unhealthy obesity, and together these findings point toward the fact that lower liver fat may be a hallmark of metabolically benign obesity, the researchers said.

To test their hypothesis, they looked at 16 pairs of monozygotic twins, ages 22 to 36, in which one was thin and the other obese. The mean difference in weight was 17.4 kg (38.4 lbs).

Two metabolically different subgroups emerged, they reported. Among the twin pairs with similar levels of liver fat, there were no differences between lean and obese twins in glucose and insulin curves during an oral glucose tolerance test (OGTT), and they had similar profiles regarding insulin resistance and insulin sensitivity.

But among the pairs where the obese twin had more liver fat, the researchers found a significantly higher area under the curve (AUC) for glucose (23%, P=0.028) and insulin (78%,P=0.028) during the OGTT.

These twins also had a 119% higher homeostasis model assessment-estimated insulin resistance (HOMA-IR), signaling worse insulin resistance, and a 55% lower Matsuda index, revealing diminished insulin sensitivity, than their lean counterparts (P=0.018 and P=0.028, respectively).

The heavy twins in these pairs also had significantly higher low density lipoprotein cholesterol and lower high density lipoprotein cholesterol than their thin twins, and a trend toward higher blood pressure.

When looking at the cellular aspects of subcutaneous adipose tissue — the more preferable adipose tissue — and gene expression in these pairs, the researchers found that among twins with similar levels of liver fat, the heavier twin had 11% more of these adipocytes.

But when the obese twin had more liver fat, they had 8% fewer adipocytes than their lean counterparts, the researchers reported.

These twins also had significant differences from their lean counterparts in terms of downregulated mitochondrial pathways, downregulated adipocyte differentiation pathways, and downregulated lipolysis pathways, as well as elevated chronic inflammatory response pathways and circulating hsCRP levels in their subcutaneous adipose tissue.

On the other hand, there were no differences in any of these factors for the twin pairs that had similar levels of liver fat, they reported. Indeed, the researchers wrote, these metabolically healthy pairs had “remarkably similar profiles in numerous measures” despite their clear differences in weight.

“Our results suggest that maintenance of high mitochondrial transcription and lack of inflammation in subcutaneous adipose tissue are associated with low liver fat and metabolically healthy obesity,” they concluded.

The study was limited by a small sample size and a cross-sectional design that cannot show causality.