calorie-restricted diet, obesity, and cancer - dr. florin selaru

Slide 1: 

Gastroenterologist Research lab at Johns Hopkins Study cancers of the GI tract Early diagnosis in conditions that predispose to cancer formation Primary sclerosing cholangitis (PSC), inflammatory bowel disease (IBD) fselaru1@jhmi.edu

Diet, Obesity  ? Cancer : 

Diet, Obesity  ? Cancer Florin M. Selaru, M.D. Assistant Professor of Medicine, Gastroenterology and Hepatology Johns Hopkins University fselaru1@jhmi.edu

What is cancer? : 

What is cancer? Inappropriate growth of cells When is cell growth needed? Fetus  adult In adult, there is need to replace cells lost to normal/abnormal processes Wound repair Inside of GI tract is renewed every few weeks The circulating cells in blood are renewed every few weeks The growth of cells is tightly regulated When control mechanisms become abnormal, cancer may arise

Cancer causes : 

Cancer causes Historically, researchers concentrated on genetics and gene mutations Genes = sentences Gene mutation – the letters in the words that form the sentence are altered Either the sentence is unintelligible or it means something else Recently, diet and obesity came into focus

Topics : 

Topics Caloric restriction Does it prolong life? Does it have anything to do with cancer? Is there need (or room) for caloric restriction in the general population? Can we modify cancer risk through diet?

How do we study cancer? : 

How do we study cancer? Experimental models Yeast Mice Primates (monkeys) Many conclusions drawn in these models hold true for humans

Topics : 

Topics Does caloric restriction prolong life?

Yeast : 

Yeast Species of fungus Widely used for baking and for beer production Caloric restriction in yeasts Life span increased by up to 50% when yeasts were fed 60-80% of usual amount In people, this is the equivalent to approximately 40 additional years of life

Mice : 

Mice Same moderate reduction in amount of food (20-40%) Longevity increased by 50% Same results in other experimental models, including monkeys McCay, C. M., Crowell, M. F. & Maynard, L. A. The effect of retarded growth upon the length of life span and upon the ultimate body size. J. Nutr. 10, 63–79 (1935).

Topics : 

Topics Does caloric restriction decrease the occurrence of cancer?

Animal models : 

Animal models Mice on low fat diet (LFD), or on high-fat diet (HFD) Looked at liver cells (hepatocytes) Proliferation (growth of cells) is much increased in cells from HFD-fed animals Apoptosis (cell suicide) – decreased in HFD

End result : 

End result High fat diet MORE growth LESS death Yes, this means cancer is more likely. EJ Park et al. Cell, 2010

Topics : 

Topics Is there need (or room) for caloric restriction in the general population?

Just adults? : 

Just adults? Prevalence of Overweight* Among U.S. Children and Adolescents (Aged 2 –19 Years)National Health and Nutrition Examination Surveys

Forget mice. : 

Forget mice. Is there a real connection between overweight-obesity and cancer in HUMANS? Yes Cancer related mortality increases by 50% when BMI is more than 25 (overweight to obese area) Liver cancer appears to be highly increased Men with BMI 35-40 have a 4.5 FOLD increase in risk of liver cancer In part related to the fact that obesity is associated with fat in the liver Bianchini et al., 2002; Calle and Kaaks, 2004; Calle et al., 2003.

Why is obesity on the rise? : 

Why is obesity on the rise? Simple experimental design: Mice followed for several generations The obesity became worse from generation to generation Maternal obesity before and during pregnancy Affects the establishment of body weight regulatory mechanisms in her baby Maternal obesity could promote obesity in the next generation

Topics : 

Topics Can we modify cancer risk through diet?

What gene is changed by caloric restriction? : 

What gene is changed by caloric restriction? Cohen HY, et al. Science 305:390-392, 2004.

Can we increase SIRT1 without eating less? : 

Can we increase SIRT1 without eating less? Yes. Resveratrol In yeast, reseveratrol increases life span Later, the findings reproduced in other organisms In mice the results are not very consistent Howitz KT, Bitterman KJ, Cohen HY, et al. (September 2003). "Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan". Nature 425 (6954): 191–6.

Resveratrol : 

Resveratrol Skin of red grapes Red wine The amount of resveratrol in red wine does not appear to be enough to actually prolong our lives…

Mice getting more overweight from one generation to the next : 

Mice getting more overweight from one generation to the next Previous research the addition of a methyl group to certain genes could prevent this phenomenon These methyl groups are found in diet folic acid, vitamin B12, betaine and choline Mice fed regular diet or diet supplemented with these components Waterland RA et al. 2008

Obese mice : 

Obese mice

Watch the diet! : 

Watch the diet!

Exercise : 

Exercise

What is on the horizon? : 

What is on the horizon?

What is on the horizon? : 

What is on the horizon? More basic science studies to clearly identify the cause to effect relationship between various dietary components and cancer reduction Rigorous clinical studies to assess the effects of various dietary components and cancer reduction

Thank you! : 

Thank you! fselaru1@jhmi.edu