2015 Awards

Spring 2015 Faculty Research Grantees

GRANT CATEGORY: Prevention of Obesity & Diet-Related Disease

Title: Linking environmental and dietary factors to the anti-carcinogenic effects of the Mediterranean Lifestyle

Amount Awarded: $100,000 (two year grant)

Timeframe: June 1, 2015 - May 31, 2017

PI: Douglas G. Mashek, PhD, Associate Professor, Department of Food Science & Nutrition, College of Food, Agriculture and Natural Resource Sciences, U of M

Co-Investigators: Li Li Ji, PhD, Director, School of Kinesiology, Professor and Director, Laboratory of Physiological Hygiene and Exercise Science, U of M

Guisheng Song, PhD, Assistant Professor, Department of Medicine: Division of Gastroenterology, Hepatology & Nutrition

Abstract: The Mediterranean Diet (MD), often considered the gold standard of diets, reduces the risk of cancer as well as other metabolic diseases. However, the biological mechanism defining how the MD reduces disease risk is largely unknown. Early studies suggested consumption of resveratrol, a bioactive compound in red wine, activated the protein sirtuin 1 (SIRT1), a protein deacetylase well documented to increase lifespan and decrease aging related diseases including cancer. However, subsequent work has shown that effects of resveratrol on SIRT1 are not specific and require supraphysiological doses. Herein, we show preliminary data that point towards a viable and novel biological mechanism that links the MD to SIRT1 activation. We show that the fatty acid oleate, which is enriched in foods common to the MD, such as olive oil and nuts, is a direct activator of SIRT1. Interestingly, dietary oleate must first be stored in cellular triacylglycerol and subsequently undergo lipolysis before it can activate SIRT1; the enzyme adipose triglyceride lipase (ATGL) is responsible for the lipolytic cleavage of oleate from triacylglycerol stores. In support, our preliminary data also show that overexpression of ATGL reduces proliferation in hepatocellular carcinoma (HCC) cell lines and in hepatocytes stimulated by growth factors. Based on these studies, we hypothesize that dietary oleate will synergize with exercise or calorie restriction, processes known to induce lipolysis, to attenuate HCC development. Thus, the objective is to determine the interaction between dietary oleate (e.g. olive oil) and either exercise or caloric restriction on HCC development in carcinogen-induced murine models of HCC. We expect these studies to help define a novel biological mechanism describing the health benefits of the Mediterranean Diet/Lifestyle, and provide strong preliminary data to pursue external funds for both mechanistic and translational studies in cancer prevention and treatment.