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Abstract

Much evidence support a link between obesity and gastrointestinal cancers however the mechanisms responsible for this relationship have not yet been fully elucidated. Secreted adipokines and cytokines from adipocytes, together with the abundant availability of lipids from adipocytes in the tumor microenvironment promote adhesion, migration and invasion of tumor cells and support tumor progression and uncontrolled growth. One of the targets predisposed to the deleterious effects exerted by secretions from adipose tissue from obese is the cellular mitochondrion. Mitochondrial oxidative metabolism plays a key role in meeting energetic demands of cells by oxidative phosphorylation (OxPhos). Typical events linking adiposity to gastrointestinal cancer are: (a) the dynamic relationship that exists among glycolysis, the tricarboxylic acid cycle, and OxPhos; (b) the evidence of impaired mitochondrial dysfunction in gastrointestinal cancers (c) the mechanisms by which mitochondrial dysfunction can predispose to cancer. We have proposed that impaired OxPhos could increase susceptibility to colon cancer since OxPhos is sensitive to a large number of factors intrinsic to the host. Summarizing several studies including ours we suggest that one of the most important links between secretions from adipose tissue from obese subjects and gastrointestinal cancer progression resides on the mitochondrial dysfunction of gastrointestinal cells induced by adipocyte's secretions. Our recent studies pinpoint that one of the direct links between secretions from adipose tissue from obese subjects is mediated by leptin. Understanding the molecular mechanisms whereby obesity increases gastrointestinal cancer risk will help in designing novel strategies to prevent the increasing numbers of cases affected by obesity-related gastrointestinal cancer.

Biography

Betty Schwartz received her PhD from Ben-Gurion University, Beer-Sheva, Israel. From 1990 to 1993 she was a postdoctoral fellow at the University of San- Francisco, California. From 1996 onwards she is appointed as Associate Professor at the Institute of Biochemistry, Food Science and Nutrition at the Hebrew University of Jerusalem, Israel. From 2005-2011 she served as Head of the School of Nutritional Sciences. From 2003-2004 she is a visiting scientist at the Department of Cancer Biology, M. D. Anderson Cancer Center, Houston, TX. Research interests are focused on the anticarcinogenic and anti-inflammatory effects of nutrients. She has published more than 90 papers in high impact journals and serves as an editorial board member in several.

Email: betty.schwartz@mail.huji.ac.il