First Fruit Fly Model of Diet-Induced Type 2 Diabetes Shows How High-Sugar Diet Affects Heart; New Therapeutic Opportunities

Jan. 15, 2013 — Regularly consuming sucrose — the type of sugar found in many sweetened beverages — increases a person’s risk of heart disease. In a study published January 10 in the journal PLOS Genetics, researchers at Sanford-Burnham Medical Research Institute and Mount Sinai School of Medicine used fruit flies, a well-established model for human health and disease, to determine exactly how sucrose affects heart function. In addition, the researchers discovered that blocking this cellular mechanism prevents sucrose-related heart problems.

Cardiac fibrosis (shown in purple), a hallmark of heart disease, is clearly increased in fruit flies on a high-sugar diet (right), as compared to flies on a normal diet (left). (Credit: Image courtesy of Sanford-Burnham Medical Research Institute)

“Our study reveals a number of specific sugar-processing enzymes that could be targeted with therapies aimed at reducing sucrose’s unhealthy effects on the heart,” said Karen Ocorr, Ph.D., research assistant professor at Sanford-Burnham and the study’s corresponding author.

Diabetic fruit flies with heart problems

The research team was the first to model heart disease caused by type 2 diabetes in fruit flies. They achieved this simply by feeding the flies a diet high in sucrose. High-sucrose flies showed many classic signs of human type 2 diabetes, including high blood sugar and insulin signaling defects. The team also saw signs of diabetes-induced heart malfunction in these flies — deteriorating heart function, cardiac arrhythmia and fibrosis.

Next the researchers wanted to know exactly what sucrose is doing inside the flies’ cells that makes it harmful to hearts. To answer this question, they looked for molecular networks that are triggered or altered by sucrose.

The team eventually pinpointed one particular biochemical system, called the hexosamine pathway. This series of biochemical reactions normally plays only a minor role in the way cells process sugar to produce energy. But some research also suggests that the hexosamine pathway is linked to diabetes in humans.

“It’s remarkable that we’re able to use the fruit fly as a discovery tool for elucidating basic molecular mechanisms, not only of many types of heart disease, but also dietary influences that help us understand what happens in human hearts,” added Rolf Bodmer, Ph.D., professor at Sanford-Burnham and a senior author of the study.

Dampening sugar’s negative effect on the heart

The researchers further probed the hexosamine pathway in their new diabetes model. They found that artificially increasing sucrose-processing via the hexosamine pathway harms the heart. In contrast, when they specifically blocked this pathway, they prevented some of the high-sucrose induced heart defects, such as cardiac arrhythmias.

“Diet-induced heart damage is one of our society’s most serious health issues. Our flies now give us a tool to explore the role of high dietary sugar, and the means to identify treatments in the context of the whole body,” said Ross Cagan, Ph.D., professor at Mount Sinai School of Medicine and a senior author of this study.


Story Source:

The above story is reprinted from materials provided bySanford-Burnham Medical Research Institute. The original article was written by Heather Buschman.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.


Journal Reference:

  1. Jianbo Na, Laura Palanker Musselman, Jay Pendse, Thomas J. Baranski, Rolf Bodmer, Karen Ocorr, Ross Cagan. A Drosophila Model of High Sugar Diet-Induced CardiomyopathyPLoS Genetics, 2013; 9 (1): e1003175 DOI: 10.1371/journal.pgen.1003175
Sanford-Burnham Medical Research Institute (2013, January 15). First fruit fly model of diet-induced type 2 diabetes shows how high-sugar diet affects heart; New therapeutic opportunities. ScienceDaily. Retrieved January 27, 2013, from http://www.sciencedaily.com/releases/2013/01/130117084932.htm

Fructose Has Different Effect Than Glucose On Brain Regions That Regulate Appetite

Jan. 1, 2013 — In a study examining possible factors regarding the associations between fructose consumption and weight gain, brain magnetic resonance imaging of study participants indicated that ingestion of glucose but not fructose reduced cerebral blood flow and activity in brain regions that regulate appetite, and ingestion of glucose but not fructose produced increased ratings of satiety and fullness, according to a preliminary study published in the January 2 issue of JAMA.


 

“Increases in fructose consumption have paralleled the increasing prevalence of obesity, and high-fructose diets are thought to promote weight gain and insulin resistance. Fructose ingestion produces smaller increases in circulating satiety hormones compared with glucose ingestion, and central administration of fructose provokes feeding in rodents, whereas centrally administered glucose promotes satiety,” according to background information in the article. “Thus, fructose possibly increases food-seeking behavior and increases food intake.” How brain regions associated with fructose- and glucose-mediated changes in animal feeding behaviors translates to humans is not completely understood.

Kathleen A. Page, M.D., of Yale University School of Medicine, New Haven, Conn., and colleagues conducted a study to examine neurophysiological factors that might underlie associations between fructose consumption and weight gain. The study included 20 healthy adult volunteers who underwent two magnetic resonance imaging sessions in conjunction with fructose or glucose drink ingestion. The primary outcome measure for the study was the relative changes in hypothalamic (a region of the brain) regional cerebral blood flow (CBF) after glucose or fructose ingestion.

The researchers found that there was a significantly greater reduction in hypothalamic CBF after glucose vs. fructose ingestion. “Glucose but not fructose ingestion reduced the activation of the hypothalamus, insula, and striatum — brain regions that regulate appetite, motivation, and reward processing; glucose ingestion also increased functional connections between the hypothalamic-striatal network and increased satiety.”

“The disparate responses to fructose were associated with reduced systemic levels of the satiety-signaling hormone insulin and were not likely attributable to an inability of fructose to cross the blood-brain barrier into the hypothalamus or to a lack of hypothalamic expression of genes necessary for fructose metabolism.”

Editorial: Fructose Ingestion and Cerebral, Metabolic, and Satiety Responses

Jonathan Q. Purnell, M.D., and Damien A. Fair, PA-C, Ph.D., of Oregon Health & Science University, Portland, write in an accompanying editorial that “these findings support the conceptual framework that when the human brain is exposed to fructose, neurobiological pathways involved in appetite regulation are modulated, thereby promoting increased food intake.”

“… the implications of the study by Page et al as well as the mounting evidence from epidemiologic, metabolic feeding, and animal studies, are that the advances in food processing and economic forces leading to increased intake of added sugar and accompanying fructose in U.S. society are indeed extending the supersizing concept to the population’s collective waistlines.”

 

Story Source:

The above story is reprinted from materials provided byJAMA and Archives Journals.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.


Journal Reference:

  1. Kathleen A. Page et al. Effects of Fructose vs Glucose on Regional Cerebral Blood Flow in Brain Regions Involved With Appetite and Reward PathwaysJAMA, 2013 DOI: 10.1001/jama.2012.116975
JAMA and Archives Journals (2013, January 1). Fructose has different effect than glucose on brain regions that regulate appetite.ScienceDaily. Retrieved January 3, 2013, from http://www.sciencedaily.com/releases/2013/01/130101182010.htm