In a new study, researchers have found the mechanisms through which high levels of blood lipids could lead to inflammation and, over time, more serious consequences, such as organ damage.
Inflammation is both caused by and a risk factor for many conditions. These include obesity, diabetes, and cardiovascular problems. One of the greatest reasons for inflammation is infection. When the body senses that dangerous foreign microorganisms, such as bacteria, have entered it, it unleashes an immune response.
Inflammation is a key part of that response. This turn of events is natural and usually helps maintain a state of health. Sometimes, however, inflammation occurs for reasons other than infection, and it may persist abnormally, leading to different types of damage. In a new study, the results of which feature in the journal Nature Immunology, Dr. Timo Speer and colleagues — from Saarland University in Saarbrücken, Germany — closed in on a factor that they say causes unhealthful inflammation: high triglyceride levels, which are a measure of blood fat. The study uncovered the mechanisms through which high blood fat can lead to inflammation — which, in turn, can affect other biological processes, potentially leading to organ and blood vessel damage.
The researchers conducted their study first in vitro, and then in mouse models, before studying the relevant mechanisms in human participants. They focused their research on a key inflammasome complex: nod-like receptor family pyrin domain-containing 3 (NLRP3). This is a protein complex that plays a crucial role in activating the body’s immune response. Dr. Speer and the team wanted to find out what could mistakenly set NLRP3 into motion. Their preliminary efforts revealed that abnormally high lipid levels — and, specifically, high
levels of triglycerides — were responsible for harmful inflammation. How? The researchers found that apolipoprotein C3 — a protein the liver secretes that is also present on triglyceride-rich lipoproteins — activates NLRP3, thereby triggering inflammation. In mouse models, high apolipoprotein C3 concentrations led to organ damage, the researchers say.
Working with human participants — some with chronic kidney disease and some with a history of a heart attack — the researchers found that higher apolipoprotein C3 may contribute to kidney
damage as well as vascular problems. High apolipoprotein C3 levels were also associated with an increased risk of mortality from all causes.
Our work has involved studying a special group of lipids, the triglycerides. We’ve been able to show that when these naturally occurring fats are present at elevated concentrations they can
alter our defense cells in such a way that the body reacts as if responding to a bacterial infection," explains Dr. Speer. This leads to inflammation, which, if it becomes chronic, can damage the kidneys or cause atherosclerosis — the narrowing of arteries due to a buildup of deposits on the inner arterial wall. And atherosclerosis is one of the main causes of heart attacks and strokes.
These findings, the researchers argue, suggest that by targeting excessive apolipoprotein C3, specialists may eventually be able to fight unhealthful inflammation. It will also be important, they say, to focus on the ways in which diet can affect levels of blood fats. Put another way, we can now say that adopting a low-fat diet can significantly extend the life expectancy of high-risk patients, such as those with diabetes or those whose blood pressure is too high, notes Dr. Speer.
This is because blood triglyceride levels tend to increase in people with high-fat diets. As a result of biochemical changes, the triglycerides develop toxic properties that activate the body’s innate immune system. This initiates a series of self-destructive processes, including those in which the walls of the arteries are attacked and the blood vessels become occluded, reducing blood flow, Dr. Speer adds. Nevertheless, he concludes that he and his colleagues hope that their results will help in developing new strategies for treating and preventing these life-threatening diseases."
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