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Citrus fruits could help prevent obesity-related heart disease, liver disease, diabetes

August 21, 2016

PHILADELPHIA, Aug. 21, 2016 -- Oranges and other citrus fruits are good for you -- they contain plenty of vitamins and substances, such as antioxidants, that can help keep you healthy. Now a group of researchers reports that these fruits also help prevent harmful effects of obesity in mice fed a Western-style, high-fat diet.

The researchers are presenting their work today at the 252nd National Meeting & Exposition of the American Chemical Society (ACS). ACS, the world's largest scientific society, is holding the meeting here through Thursday. It features more than 9,000 presentations on a wide range of science topics.

"Our results indicate that in the future we can use citrus flavanones, a class of antioxidants, to prevent or delay chronic diseases caused by obesity in humans," says Paula S. Ferreira, a graduate student with the research team.

More than one-third of all adults in the U.S. are obese, according to the U.S. Centers for Disease Control and Prevention. Being obese increases the risk of developing heart disease, liver disease and diabetes, most likely because of oxidative stress and inflammation, Ferreira says. When humans consume a high-fat diet, they accumulate fat in their bodies. Fat cells produce excessive reactive oxygen species, which can damage cells in a process called oxidative stress. The body can usually fight off the molecules with antioxidants. But obese patients have very enlarged fat cells, which can lead to even higher levels of reactive oxygen species that overwhelm the body's ability to counteract them.

Citrus fruits contain large amounts of antioxidants, a class of which are called flavanones. Previous studies linked citrus flavanones to lowering oxidative stress in vitro and in animal models. These researchers wanted to observe the effects of citrus flavanones for the first time on mice with no genetic modifications and that were fed a high-fat diet.

The team, at Universidade Estadual Paulista (UNESP) in Brazil, conducted an experiment with 50 mice, treating them with flavanones found in oranges, limes and lemons. The flavanones they focused on were hesperidin, eriocitrin and eriodictyol. For one month, researchers gave groups either a standard diet, a high-fat diet, a high-fat diet plus hesperidin, a high-fat diet plus eriocitrin or a high-fat diet plus eriodictyol.

The high-fat diet without the flavanones increased the levels of cell-damage markers called thiobarbituric acid reactive substances (TBARS) by 80 percent in the blood and 57 percent in the liver compared to mice on a standard diet. But hesperidin, eriocitrin and eriodictyol decreased the TBARS levels in the liver by 50 percent, 57 percent and 64 percent, respectively, compared with mice fed a high-fat diet but not given flavanones. Eriocitrin and eriodictyol also reduced TBARS levels in the blood by 48 percent and 47 percent, respectively, in these mice. In addition, mice treated with hesperidin and eriodictyol had reduced fat accumulation and damage in the liver.

"Our studies did not show any weight loss due to the citrus flavanones," says Thais B. Cesar, Ph.D., who leads the team. "However, even without helping the mice lose weight, they made them healthier with lower oxidative stress, less liver damage, lower blood lipids and lower blood glucose."

Ferreira adds, "This study also suggests that consuming citrus fruits probably could have beneficial effects for people who are not obese, but have diets rich in fats, putting them at risk of developing cardiovascular disease, insulin resistance and abdominal obesity."

Next, the team will explore how best to administer these flavanones, whether in citrus juice, by consuming the fruit or developing a pill with these antioxidants. In addition, the team plans to conduct studies involving humans, Cesar says.

Cesar acknowledges funding from the Support Program for Scientific Development of the School of Pharmaceutical Sciences at UNESP and by Citrosuco, an orange juice production company in Matão, Sao Paulo, Brazil.
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Title

Citrus flavonones decreases oxidative stress in the liver and blood serum caused by highfat diet feeding in C57BL/6J mice

Abstract

High-fat diet and adipose tissue accumulation commonly leads to an increased oxidative stress and inflammation, contributing to the development of chronic diseases observed in obesity, such as diabetes mellitus and cardiovascular diseases. Citrus flavonoids have biological properties capable of attenuating oxidative stress, protecting against metabolic disorders resulting from obesity. In the present work we studied the effect of the citrus flavonones hesperidin, eriocitrin and eriodictyol (100, 200 and 200 mg/kg body weight, respectively) over oxidative stress in the blood serum and liver of C57BL/6J male mice fed high fat diet (45% kcal from saturated fat) for 30 days. Mice fed highfat diet showed visceral fat accumulation and increased TBARS levels in the blood serum (80%) and in the liver (57%), while hesperidin, eriocitrin and eriodictyol increased the serum total antioxidant capacity (7%, 9% and 6%, respectively) and decreased the TBARS levels in the liver (50 %, 57 % and 64 %, respectively). Eriocitrin and eriodictyol also decreased the blood serum TBARS levels in 48% and 47%, respectively. In addition, the liver fat accumulation and damaged hepatocytes (observed by histology analyses) was efficiently reduced by hesperidin and eriodictyol, and the serum levels of LDLC was reduced in 28% by hesperidin. These results showed that hesperidin, eriocitrin and eriodictiol have protective effect against oxidative stress caused by high-fat diet feeding in mice, as indicated by reduced liver damage, liver fat accumulation, and TBARS levels in the liver or serum, making them potential candidates to prevent tissue damage and the development of metabolic dysfunction associated to chronic diseases caused by obesity.

American Chemical Society

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