Het gevaar van vetrijke maaltijden*
Vetrijke maaltijden kunnen volgens twee studies leiden tot ontstekingen van de bloedvaten en bij kanker de kans op uitzaaiingen fors verhogen. In de ene studie kregen muizen slechts twee weken een vetrijke maaltijd. In die twee weken was het vet rond de slagaders flink ontstoken waardoor de kans op ontsteking van de slagaders zelf en daardoor de kans op aderverkalking flink hoger was. In de tweede studie kregen muizen met een
geïmplanteerd kankergezwel of een vetrijk- of een vetarmdieet. Met speciale technieken werden de tumoren en mogelijke uitzaaiingen in kaart gebracht. Het dieet veranderde niet de tumor zelf doch de hoeveelheid uitzaaiingen was bij een vetrijkdieet 300% hoger.
High-fat diets inflame fat tissue surrounding blood vessels
A study by researchers at the University of Cincinnati (UC) shows that high-fat diets, even if consumed for a short amount of time, can inflame fat tissue surrounding blood vessels, possibly contributing to cardiovascular disease.
These findings will be published in the American Heart Association journal Circulation Research .
Neal Weintraub, MD, and colleagues examined adipose tissue-or fat-surrounding the coronary arteries of humans. The researchers found these fat cells to be highly inflamed, suggesting that they could trigger inflammation of the blood vessels, an important component of atherosclerosis.
They also found that the inflammation of fat tissues around the arteries of mice is increased by feeding the animals a high-fat diet for just two weeks.
"This is independent of weight gain or blood lipids-cholesterol levels," says Weintraub, senior author of the study and chair of the cardiovascular diseases division at UC.
Weintraub says that high fat diets contribute to atherosclerosis-or the hardening of arteries-in a number of ways.
"Elevated blood lipids-or cholesterol levels-can worsen with the intake of high fat diets, and this is known to contribute to atherosclerosis," he says. "However, many patients who consume high fat diets do not exhibit abnormal lipid profiles but still develop atherosclerosis nonetheless.
"These new findings suggest a direct link between poor dietary habits and inflammation of blood vessels, mediated by the fat cells surrounding the blood vessel wall."
Weintraub adds that the diet fed to the mouse models was not unlike the diets consumed by many Americans.
"It produced striking abnormalities of the fat tissue surrounding blood vessels in a very short period of time," he says. "This is a warning to those who say there isn't a problem because their weight and cholesterol levels are under control. Lipid profiles don't hold all the answers.
"Bad dietary habits can lead to a number of problems, and this suggests that a high fat diet is detrimental in ways we didn't previously understand."
Weintraub says there is no real way to measure the effects of poor dietary habits on fat tissue surrounding blood vessels.
"We don't know why these cells are so responsive to high-fat diets," he says. "We must now conduct further experiments to answer these types of questions."
http://www.uc.edu/
Measuring The Precise Impact Of Fat On Cancer Spread
Researchers at Purdue University have precisely measured the impact of a high-fat diet on the spread of cancer, finding that excessive dietary fat caused a 300 percent increase in metastasizing tumor cells in laboratory
animals.
The researchers used an imaging technique to document how increasing fat content causes cancer cells to undergo changes essential to metastasis. Then they used another technique to count the number of cancer cells in the bloodstream of mice fed a high-fat diet compared to animals fed a lean
diet.
The findings suggest that the combined tools represent a possible new diagnostic technique to determine whether a patient's cancer is spreading, said Ji-Xin Cheng, an assistant professor in Purdue's Weldon School of Biomedical Engineering and Department of Chemistry.
"It is generally accepted that diet and obesity are accountable for 30 percent of preventable causes of cancer, but nobody really knows why," Cheng said. "These findings demonstrate that an increase in lipids leads directly to a rise in cancer metastasis."
Researchers have theorized that tumor cells need more lipids than ordinary tissues to provide energy and material for tumor growth and metastasis.
"Before this work, however, most of the evidence was anecdotal, but here we present a mechanistic study," said Thuc T. Le, a National Institutes of Health postdoctoral fellow at Purdue who is working with Cheng.
Findings were detailed in a paper published in the journal BMC Cancer. The paper was written by Le; Terry B. Huff, a graduate research assistant in Purdue's Department of Chemistry; and Cheng. The research is supported by the Purdue Cancer Center.
The researchers implanted a cancerous lung tumor under the skin in each of the mice studied, and the animals were separated into two groups: one fed a high-fat diet and the other a lean
diet.
The researchers then used an imaging method called coherent anti-Stokes Raman scattering, or CARS, to document how increasing lipids from fat intake induces changes to cancer cell membranes. Those changes, including processes called membrane phase separation and membrane rounding, enhance cancer metastasis.
"If the cancer cells don't have excess lipids they stick together and form very tight junctions in tumors, but increasing lipids causes them to take on a rounded shape and separate from each other," Le
said.
The change in shape is critical to the ability of cancer cells to separate and spread throughout the body via the
bloodstream.
The researchers then used another technique, called intravital flow cytometry, to count the number of cancer cells in the bloodstream of the mice. The technique works by shining a laser though the skin and into blood vessels, where the dyed cancer cells are visible.
Results showed the increase in lipids had no impact on the original tumors implanted in the mice. However, the rate of metastasis rose a dramatic 300 percent in the mice fed a high-fat
diet.
The researchers later also examined the animals' lungs and counted the number of cancer cells that had migrated to the lungs as a result of metastasis. Those findings supported the other results showing increased metastasis in animals fed a high-fat
diet.
The researches used the imaging and cell-counting tools to document that linoleic acid, which is predominant in polyunsaturated fats, caused increasing membrane phase separation, whereas oleic acid, found in monounsaturated fats, did not. Increased membrane phase separation could improve the opportunity of circulating tumor cells to adhere to blood vessel walls and escape to organs far from the original tumor site. The new findings support earlier evidence from other research that consuming high amounts of polyunsaturated fat may increase the risk of cancer
spreading.
The findings suggest that combining CARS and intravital flow cytometry represents a possible new diagnostic tool to screen patients for cancer. The tool can be used to count lipid-rich tumor cells circulating in a patient's blood by shining a laser through the skin and into blood vessels. Because lipids can be detected without the need for dyes, the technique might be developed into a convenient method to diagnose whether a patient's cancer is spreading aggressively, Cheng
said.
"These findings open the possibility of an entirely new, relatively simple method for diagnosing whether cancer is metastasizing," he said.
Future work will focus on not only how obesity increases metastasis but also how it might play a direct role in initiating the development of
cancers.
The research has been funded by the National Institutes of Health.
Writer: Emil Venere
ABSTRACT
Coherent Anti-Stokes Raman Scattering Imaging of Lipids in Cancer Metastasis
Thuc T Le1, Terry B Huff2 and Ji-Xin Cheng*1,2,3
1Weldon School of Biomedical Engineering, Purdue University; 2Department of Chemistry, Purdue University; 3Purdue Cancer Center
Background: Lipid-rich tumours have been associated with increased cancer metastasis and aggressive clinical behaviours. Nonetheless, pathologists cannot classify lipid-rich tumours as a clinically distinctive form of carcinoma due to a lack of mechanistic understanding on the roles of lipids in cancer development. Methods: Coherent anti-Stokes Raman scattering (CARS) microscopy is employed to study cancer cell behaviours in excess lipid environments in vivo and in vitro. The impacts of a high-fat diet on cancer development are evaluated in a Balb/c mice cancer model. Intravital flow cytometry and histology are employed to enumerate cancer cell escape to the bloodstream and metastasis to lung tissues, respectively. Cancer cell motility and tissue invasion capability are also evaluated in excess lipid environments. Results: CARS imaging reveals intracellular lipid accumulation is induced by excess free fatty acids (FFAs). Excess FFAs incorporation onto cancer cell membrane induces membrane phase separation, reduces cell-cell contact, increases surface adhesion, and promotes tissue invasion. Increased plasma FFAs level and visceral adiposity are associated with early rise in circulating tumour cells and increased lung metastasis. Furthermore, CARS imaging reveals FFAs-induced lipid accumulation in primary, circulating, and metastasized cancer cells. Conclusion: Lipid-rich tumours are linked to cancer metastasis through FFAs-induced physical perturbations on cancer cell membrane. Most importantly, the revelation of lipid-rich circulating tumour cells suggests possible development of CARS intravital flow cytometry for label-free detection of early-stage cancer
metastasis.
tact: Emil Venere
Purdue University (April
2009)
