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Preclinical research suggests a high-fat diet is associated with red blood cell (RBC) dysfunction and helps explain how these dysfunctional cells may mediate atherosclerosis.
The researchers believe their findings may have implications for the pathogenesis of atherosclerosis in obesity, but the work may aid the study of other health conditions as well, such as thrombosis in the context of cancer.
The team detailed their findings in Circulation.
“Obesity caused by chronic consumption of a high-calorie, high-fat diet is a worldwide epidemic, representing one of the greatest threats to global health,” said principal investigator Vladimir Bogdanov, PhD, of the University of Cincinnati in Ohio.
“White blood cells play a key role in fueling adipose tissue inflammation and insulin resistance in obesity and also promote the clogging of arteries, or atherosclerosis, setting the stage for heart attack and stroke. While these outcomes linked with a high-fat diet and fat in the blood on white blood cells have been shown in animal models and humans, the impact of high-fat diets on other bone marrow-derived cells, like red blood cells, is not well-defined.”
“Evidence is emerging that red blood cells play an important regulatory role in the development of atherosclerosis, binding pro-inflammatory proteins that cause dysfunction in the inner lining of the blood vessel wall—the endothelium. We explored how a high fat-diet causes red blood cell dysfunction in this study.”
Dr Bogdanov and his team fed a 60% high-fat diet to mice for 12 weeks and compared these animals to control mice that received a normal diet.
There was an increase in the level of chemokines bound to the RBCs of mice that received the high-fat diet. These chemokines were bound to RBCs via the Duffy antigen receptor for chemokines.
The researchers exposed RBCs from mice on the high-fat diet to an endothelial monolayer in vitro, and they observed “significantly enhanced” macrophage transendothelial migration. They said this confirms the functional importance of RBC-bound chemokines in the setting of a high-fat diet.
“In red blood cells from animal models fed a high-fat diet, there was an increase in cholesterol found in the cell membrane and phosphatidylserine levels, promoting inflammatory reactions,” Dr Bogdanov added.
“Phosphatidylserine is a phospholipid membrane component which plays a key role in the cycle of cells. When red blood cells from the animals being fed the high-fat diet were injected into a control group, eating a normal diet, there was a 3-fold increase in their spleens’ uptake of red blood cells. The spleen is involved in the removal of blood cells, as well as systemic inflammation.”
“All of these findings show that the dysfunction of red blood cells, corresponding with dysfunction of the lining of blood vessels, occurs very early in diet-induced obesity and may play a part in the formation of atherosclerosis. Diets high in saturated fat have long been associated with endothelial dysfunction, the precursor to atherosclerosis, but, to our knowledge, the effects of high-fat diet on red blood cells have not been rigorously examined.”
Dr Bogdanov noted that, in humans, high cholesterol is associated with alterations in RBCs that are improved by treatment with statins. But the majority of obese humans do not have severe high cholesterol, as was the case with the animals in this study.
The researchers are now working on translating their findings to humans. 
Preclinical research suggests a high-fat diet is associated with red blood cell (RBC) dysfunction and helps explain how these dysfunctional cells may mediate atherosclerosis.
The researchers believe their findings may have implications for the pathogenesis of atherosclerosis in obesity, but the work may aid the study of other health conditions as well, such as thrombosis in the context of cancer.
The team detailed their findings in Circulation.
“Obesity caused by chronic consumption of a high-calorie, high-fat diet is a worldwide epidemic, representing one of the greatest threats to global health,” said principal investigator Vladimir Bogdanov, PhD, of the University of Cincinnati in Ohio.
“White blood cells play a key role in fueling adipose tissue inflammation and insulin resistance in obesity and also promote the clogging of arteries, or atherosclerosis, setting the stage for heart attack and stroke. While these outcomes linked with a high-fat diet and fat in the blood on white blood cells have been shown in animal models and humans, the impact of high-fat diets on other bone marrow-derived cells, like red blood cells, is not well-defined.”
“Evidence is emerging that red blood cells play an important regulatory role in the development of atherosclerosis, binding pro-inflammatory proteins that cause dysfunction in the inner lining of the blood vessel wall—the endothelium. We explored how a high fat-diet causes red blood cell dysfunction in this study.”
Dr Bogdanov and his team fed a 60% high-fat diet to mice for 12 weeks and compared these animals to control mice that received a normal diet.
There was an increase in the level of chemokines bound to the RBCs of mice that received the high-fat diet. These chemokines were bound to RBCs via the Duffy antigen receptor for chemokines.
The researchers exposed RBCs from mice on the high-fat diet to an endothelial monolayer in vitro, and they observed “significantly enhanced” macrophage transendothelial migration. They said this confirms the functional importance of RBC-bound chemokines in the setting of a high-fat diet.
“In red blood cells from animal models fed a high-fat diet, there was an increase in cholesterol found in the cell membrane and phosphatidylserine levels, promoting inflammatory reactions,” Dr Bogdanov added.
“Phosphatidylserine is a phospholipid membrane component which plays a key role in the cycle of cells. When red blood cells from the animals being fed the high-fat diet were injected into a control group, eating a normal diet, there was a 3-fold increase in their spleens’ uptake of red blood cells. The spleen is involved in the removal of blood cells, as well as systemic inflammation.”
“All of these findings show that the dysfunction of red blood cells, corresponding with dysfunction of the lining of blood vessels, occurs very early in diet-induced obesity and may play a part in the formation of atherosclerosis. Diets high in saturated fat have long been associated with endothelial dysfunction, the precursor to atherosclerosis, but, to our knowledge, the effects of high-fat diet on red blood cells have not been rigorously examined.”
Dr Bogdanov noted that, in humans, high cholesterol is associated with alterations in RBCs that are improved by treatment with statins. But the majority of obese humans do not have severe high cholesterol, as was the case with the animals in this study.
The researchers are now working on translating their findings to humans.
Preclinical research suggests a high-fat diet is associated with red blood cell (RBC) dysfunction and helps explain how these dysfunctional cells may mediate atherosclerosis.
The researchers believe their findings may have implications for the pathogenesis of atherosclerosis in obesity, but the work may aid the study of other health conditions as well, such as thrombosis in the context of cancer.
The team detailed their findings in Circulation.
“Obesity caused by chronic consumption of a high-calorie, high-fat diet is a worldwide epidemic, representing one of the greatest threats to global health,” said principal investigator Vladimir Bogdanov, PhD, of the University of Cincinnati in Ohio.
“White blood cells play a key role in fueling adipose tissue inflammation and insulin resistance in obesity and also promote the clogging of arteries, or atherosclerosis, setting the stage for heart attack and stroke. While these outcomes linked with a high-fat diet and fat in the blood on white blood cells have been shown in animal models and humans, the impact of high-fat diets on other bone marrow-derived cells, like red blood cells, is not well-defined.”
“Evidence is emerging that red blood cells play an important regulatory role in the development of atherosclerosis, binding pro-inflammatory proteins that cause dysfunction in the inner lining of the blood vessel wall—the endothelium. We explored how a high fat-diet causes red blood cell dysfunction in this study.”
Dr Bogdanov and his team fed a 60% high-fat diet to mice for 12 weeks and compared these animals to control mice that received a normal diet.
There was an increase in the level of chemokines bound to the RBCs of mice that received the high-fat diet. These chemokines were bound to RBCs via the Duffy antigen receptor for chemokines.
The researchers exposed RBCs from mice on the high-fat diet to an endothelial monolayer in vitro, and they observed “significantly enhanced” macrophage transendothelial migration. They said this confirms the functional importance of RBC-bound chemokines in the setting of a high-fat diet.
“In red blood cells from animal models fed a high-fat diet, there was an increase in cholesterol found in the cell membrane and phosphatidylserine levels, promoting inflammatory reactions,” Dr Bogdanov added.
“Phosphatidylserine is a phospholipid membrane component which plays a key role in the cycle of cells. When red blood cells from the animals being fed the high-fat diet were injected into a control group, eating a normal diet, there was a 3-fold increase in their spleens’ uptake of red blood cells. The spleen is involved in the removal of blood cells, as well as systemic inflammation.”
“All of these findings show that the dysfunction of red blood cells, corresponding with dysfunction of the lining of blood vessels, occurs very early in diet-induced obesity and may play a part in the formation of atherosclerosis. Diets high in saturated fat have long been associated with endothelial dysfunction, the precursor to atherosclerosis, but, to our knowledge, the effects of high-fat diet on red blood cells have not been rigorously examined.”
Dr Bogdanov noted that, in humans, high cholesterol is associated with alterations in RBCs that are improved by treatment with statins. But the majority of obese humans do not have severe high cholesterol, as was the case with the animals in this study.
The researchers are now working on translating their findings to humans.