Researcher studies dietary bioactive compounds and their impact on chronic disease

IMG_2176Vitamins and minerals are well known for their essential role in maintaining health and wellness. Still, there are other, often less recognized, food components that can also make important contributions. These other components, known as dietary bioactive compounds, are present in food in small quantities, but may be making a big impact. Christopher Blesso, assistant professor in the Department of Nutritional Sciences, is studying the effects of these previously overlooked substances on low-grade inflammation in certain chronic diseases, such as heart disease, obesity and diabetes.

In his studies of lipid metabolism, Blesso examines the body’s processing of fats, cholesterol, phospholipids and other molecules. He is interested in the impact the compounds can have on lipid metabolism and the low-grade inflammation that is characteristic of these disease states. The hope is that, one day, these compounds could be used therapeutically to reduce inflammation and improve the quality of life in patients suffering from low-grade inflammatory states. Blesso focuses on high-density lipoprotein (HDL) metabolism and cholesterol, as well as dietary phospholipids, which are molecules that provide animal and plant cell membranes with structure.

Blesso’s work with dietary bioactive compounds builds on his nutritional research focused on lipid metabolism in two areas. Currently, he studies phytochemicals and their impact on HDL functionality, as well as sphingomyelin and its effects on obesity and atherosclerosis.

Phytochemicals and HDL function

Blesso investigates the effects of plant-derived chemicals, known as phytochemicals, on the protective functions of HDL particles. HDL is found in the bloodstream and protects the heart by transporting cholesterol away from arterial plaques, a process known as reverse cholesterol transport. Other protective effects HDL can provide include anti-inflammatory and antioxidant activities. Unfortunately, the HDL particles lose their protective properties in many disease states where chronic inflammation is present. Blesso’s lab investigates how dietary components influence this process and whether they can prevent HDL from becoming dysfunctional. Blesso was the principal investigator (PI) on an experiment in mice that demonstrated the protective effects of anthocyanins, a class of phytochemicals found in black elderberries. Funding for this project was majorly provided by the United States Department of Agriculture through a National Institute of Food and Agriculture (NIFA) Seed Grant.

IMG_2124Research from Blesso’s lab, led by his former master’s student Nicholas Farrell, was able to demonstrate the protective effects of anthocyanin-containing black elderberry extract (BEE) supplementation for the first time. Chronic BEE supplementation resulted in a reduction in low-grade inflammation, as well as the prevention of cholesterol accumulation in arteries, or atherosclerosis, in a mouse model of heart disease. They also demonstrated protective effects of BEE on obesity-related inflammation and diabetes development in a mouse model of diet-induced obesity. His research demonstrates the potential of black elderberry, as a rich source of anthocyanins, in reducing the disease risk profile in atherosclerosis and diet-induced obesity. They are currently working on a longer-term study that further investigates the effects of BEE on the complexity of atherosclerosis in mice.

The Blesso lab has another ongoing pilot project in humans investigating the acute and chronic effects of consuming grapes on HDL functionality in metabolic syndrome. Metabolic syndrome is a condition that describes a grouping of risk factors, such as obesity, high blood pressure, insulin resistance and dyslipidemia. Together, these risk factors substantially increase the likelihood of developing heart disease and diabetes. This randomized, double-blind, placebo-controlled, crossover study is funded by the California Table Grape Commission. This project, led by graduate students Courtney Millar and Quinn Duclos, is similar to the elderberry project in that it looks at the effect of phytochemicals, this time from grapes, on HDL antioxidant and anti-inflammatory activities.

Blesso became interested in HDL after discovering that his own HDL levels were genetically low, despite living a healthy lifestyle. As a graduate student, Blesso began investigating HDL by looking at various aspects of HDL metabolism, such as the effects that eggs have on HDL cholesterol. He then went on to complete post-doctoral training looking into the molecular mechanisms of how HDL protects from heart disease.

Blesso notes that most people consider HDL cholesterol to be “good” cholesterol and thus strive to raise it. He explains, however, that it may be that the quality of the HDL matters even more than the quantity.

“There has been a paradigm shift in how we consider HDL as a target for drugs and diet… We are considering how HDL is functioning in these dynamic processes, instead of just measuring a static cholesterol component. We don’t design drugs; we look at diet and how diet affects HDL cholesterol. We measure how diet affects HDL antioxidant and anti-inflammatory properties because in heart disease, HDL loses these properties.”

Sphingomyelin and atherosclerosis

Blesso’s early research on eggs segued into an interest in phospholipids, since eggs happen to be a rich source. Due to its interaction with cholesterol and other lipids, Blesso chose to focus on sphingomyelin (SM), a phospholipid found in the membranes of animal cells. SM appears in animal-based foods in varying amounts. When consumed, it is digested very slowly and can inhibit the absorption of dietary cholesterol and saturated fat. Dr. Sung Koo, head of the Department of Nutritional Sciences, conducted seminal research studies demonstrating these effects in rats over a decade ago. The ability to inhibit lipid absorption makes dietary SM a candidate for improving atherosclerosis, which is the build-up of plaques in artery walls.IMG_2174

Blesso has been the PI on experiments analyzing the effects of both egg and milk SM on obese and atherosclerotic mice. Milk SM was able to essentially reverse the damages from a high-fat diet in mouse models. Both egg and milk SM showed to have a protective effect against inflammation and fat accumulation in the liver.

In these types of studies, concentrated sources of saturated fat depleted of SM, such as butterfat, palm oil and lard, are fed to rodents to induce chronic diseases like obesity and diabetes. Blesso’s research shows, however, that when dietary SM is added to these high-fat diets, it markedly improves lipid and inflammatory markers, protecting against the metabolic issues related to saturated fat and cholesterol intake. This work was led by PhD student Greg Norris. Blesso is currently conducting a study funded by the American Egg Board to examine how egg SM influences atherosclerosis in mice.

For now, Blesso relies on studies performed on animal models, but aims to translate them to human models. In doing so, Blesso hopes to impact the dietary recommendations or help to identify novel sources of dietary bioactive compounds. For instance, Blesso notes that butter serum, the aqueous phase of butter, is largely ignored as a by-product in the anhydrous milkfat-making process, but is one of the most concentrated sources of SM. Furthermore, since SM is also found in egg yolk, egg yolk by-products could be utilized as inexpensive sources of SM.

“We used to think that whey protein was a waste product with no value. Now it’s everywhere. It is a quality protein and has some value. We are trying to see if [these dietary bioactive compounds] are efficacious in preventing disease risk,” Blesso said.

Blesso recognizes the importance of his research team, “None of what I do would be possible without my undergraduate and graduate students who work in my lab. This is a good team that we have here.”

In addition to his research, Blesso also teaches undergraduate classes and a graduate course he developed. His graduate course, Regulation of Food Intake and Energy Balance (NUSC 5398), is a special topics course offered every other spring. It focuses on the regulation of food intake and the various pathways that control appetite and satiety.

Blesso is also a recent recipient of the 2017 Dr. Lynne Goodstein and Dr. Peter Langer Award for Honors Advising, showcasing his dedication to advising his students in the Honors Program.

“I come to work every day excited about the research. I feel like my research is the fun part that I do as a hobby. I feel like I get paid to teach, but I do like teaching as well. The exciting part of research is trying to discover new things. That’s going to be what drives a forty-year career.”