14 DAY TRIAL // Big bellies (no matter if because of the beer or the junk food) represent a high risk of heart attacks and strokes. This was found by many researches, but no study could explain why the visceral fat boosts these health problems.
This appears to be explained by a new research published in the journal "Circulation" and carried out by a team of the University of Michigan Cardiovascular Center: inflammation around the visceral fat deposits could cause atherosclerosis and subsequently a heart attack, or stroke.
The team led by Dr Daniel Eitzman, M.D., a cardiologist and associate professor in the Division of Cardiovascular Medicine, investigated obese mice lacking the gene for leptin, a hormone released by fatty cells and involved in appetite, metabolism control and reproduction. When the team transplanted clusters of fatty cells from normal mice into the mutated mice, they were surprised.
"In addition to producing leptin and preventing obesity, the fat transplants became inflamed, attracting immune cells called macrophages. Since the mice were genetically identical except for leptin, this shouldn't have happened. But the inflammation was there, and it was chronic," said Eitzman.
The inflammation affected fat cells (adipocytes) and was controlled by the same factors involved in the inflammation seen in fat deposits of normal obese mice: a chemokine called MCP-1.
But as the fat was transplanted, the inflammation was caused directly by the fat, not by metabolic issues or diabetes. Atherosclerosis is known to be caused by inflammation (overreaction of the body's immune system to its own tissue). The team engineered a mouse strain, ApoE-negative, prone to high cholesterol and atherosclerosis (hardened arteries). Two groups of mutated mice received fat transplants from normal mice, and one did not, but underwent the same operation as for fat implanting.
Some ApoE-negative mice received transplants of visceral fat (from the belly, wrapping major organs), while others received transplants of subcutaneous (under skin) fat. The individuals receiving the visceral fat grew atherosclerosis at a high speed, and displayed the same inflammation level as the leptin-deficient mice. The groups that received subcutaneous fat did not have a higher risk of atherosclerosis despite boosted inflammation. The control group developed neither inflammation nor boosted atherosclerosis.
"There appeared to be an interaction between the macrophages causing the inflammation in the visceral fat, and the process of atherosclerosis. Blood vessels far from the site of the fat transplant developed increased atherosclerosis," said Eitzman. For decreasing the inflammation and atherosclerosis rates, the team employed pioglitazone, a type of thiazolidinediones (TZDs), often used against diabetes. TZDs affect the metabolism, but recently it has been found that they have an anti-inflammatory effect. The chemical decreased both the levels of macrophages, MCP-1 and atherosclerosis, in the mice transplanted with visceral fat, while in other mice it had no effect.
Now, the team is searching for factors making macrophages to invade the area and provoke inflammation, and for blood biomarkers for early signs of atherosclerosis.