Diet, Obesity, and Chronic Disease The Kratz Lab at Fred Hutch Mario Kratz, Ph.D.

©2014 Fred Hutchinson Cancer Research Center

Focus of the Kratz Lab at Fred Hutch ? ? ? ? ? ©2014 Fred Hutchinson Cancer Research Center

1990 The Obesity Epidemic Percentage of adults with BMI ≥ 30 kg/m2 No Data <10% 10%–14% Percentage of adults with BMI ≥ 30 kg/m2 ©2014 Fred Hutchinson Cancer Research Center

1993 The Obesity Epidemic Percentage of adults with BMI ≥ 30 kg/m2 No Data <10% 10%–14% 15%–19% Percentage of adults with BMI ≥ 30 kg/m2 ©2014 Fred Hutchinson Cancer Research Center

1996 The Obesity Epidemic Percentage of adults with BMI ≥ 30 kg/m2 No Data <10% 10%–14% 15%–19% Percentage of adults with BMI ≥ 30 kg/m2 ©2014 Fred Hutchinson Cancer Research Center

1999 The Obesity Epidemic Percentage of adults with BMI ≥ 30 kg/m2 No Data <10% 10%–14% 15%–19% ≥20% Percentage of adults with BMI ≥ 30 kg/m2 ©2014 Fred Hutchinson Cancer Research Center

2002 The Obesity Epidemic Percentage of adults with BMI ≥ 30 kg/m2 No Data <10% 10%–14% 15%–19% 20%–24% ≥25% Percentage of adults with BMI ≥ 30 kg/m2 ©2014 Fred Hutchinson Cancer Research Center

2005 The Obesity Epidemic Percentage of adults with BMI ≥ 30 kg/m2 No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30% Percentage of adults with BMI ≥ 30 kg/m2 ©2014 Fred Hutchinson Cancer Research Center

2008 The Obesity Epidemic Percentage of adults with BMI ≥ 30 kg/m2 No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30% Percentage of adults with BMI ≥ 30 kg/m2 ©2014 Fred Hutchinson Cancer Research Center

2010 The Obesity Epidemic Percentage of adults with BMI ≥ 30 kg/m2 No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30% Percentage of adults with BMI ≥ 30 kg/m2 ©2014 Fred Hutchinson Cancer Research Center

Obesity & Chronic Disease ? ©2014 Fred Hutchinson Cancer Research Center

Obesity & Chronic Disease Risk of type 2 diabetes in relationship to obesity Colditz et al.; Ann. Intern. Med. 1995; 122: 481-6 ©2014 Fred Hutchinson Cancer Research Center

Obesity & Chronic Disease Increase in risk of dying from specific types of cancer in obese men (BMI >35 kg/m2) compared to normal weight men. Calle et al; N. Engl. J. Med. 2003; 348: 1625-38 ©2014 Fred Hutchinson Cancer Research Center

Obesity & Chronic Disease Risk of cardiovascular disease in relationship to obesity & diabetes 10-year risk of developing cardiovascular disease WOMEN Normal weight Obese No diabetes 6.2% 9.3% Diabetes 9.4% 10-year risk of developing cardiovascular disease MEN Normal weight Obese No diabetes Diabetes Fox et al.; Diabetes Care 2008; 31: 1582-4 ©2014 Fred Hutchinson Cancer Research Center

Obesity & Chronic Disease Risk of cardiovascular disease in relationship to obesity & diabetes 10-year risk of developing cardiovascular disease WOMEN Normal weight Obese No diabetes 6.2% 9.3% Diabetes 9.4% 41.9% 10-year risk of developing cardiovascular disease MEN Normal weight Obese No diabetes Diabetes Fox et al.; Diabetes Care 2008; 31: 1582-4 ©2014 Fred Hutchinson Cancer Research Center

Obesity & Chronic Disease Risk of cardiovascular disease in relationship to obesity & diabetes 10-year risk of developing cardiovascular disease WOMEN Normal weight Obese No diabetes 6.2% 9.3% Diabetes 9.4% 41.9% 10-year risk of developing cardiovascular disease MEN Normal weight Obese No diabetes 11.9% 22.8% Diabetes 33.2% 47.6% Fox et al.; Diabetes Care 2008; 31: 1582-4 ©2014 Fred Hutchinson Cancer Research Center

Obesity & Chronic Disease ? ©2014 Fred Hutchinson Cancer Research Center

Obesity & Chronic Disease ✔ But: How does being obese increase the risk for chronic disease? ©2014 Fred Hutchinson Cancer Research Center

Obesity & Chronic Disease Dyslipidemia Insulin Resistance Chronic Disease Obesity Low-Grade Chronic Systemic Inflammation Changes in Hormone Concentrations: Sex Steroid Hormones Adiponectin Leptin ©2014 Fred Hutchinson Cancer Research Center

Obesity & Chronic Disease Dyslipidemia Insulin Resistance Chronic Disease Adipose Tissue Inflammation Low-Grade Chronic Systemic Inflammation Changes in Hormone Concentrations: Sex Steroid Hormones Adiponectin Leptin ©2014 Fred Hutchinson Cancer Research Center

Introduction & Objective DASI DASI DAIRY RCT AIM DAIRY RCT CROSS- ROADS ©2014 Fred Hutchinson Cancer Research Center

Introduction & Objective DASI DASI DAIRY RCT AIM DAIRY RCT CROSS- ROADS ©2014 Fred Hutchinson Cancer Research Center

Anti-Inflammatory Milieu (AIM)-Diet Study Based on a recent publication of our group (Kratz et al.; Cell Metab. 2014; 20: 1-12), we hypothesize that excessive diurnal exposure of adipose tissue to glucose, insulin, and fatty acids triggers ‘metabolic inflammation’. Newly developed AIM diet minimizes adipose tissue exposure to glucose, insulin, and long-chain fatty acids. Dietary intervention RCT to compare the effect of the AIM diet vs. USDA-diet on: Adipose tissue inflammation Insulin resistance Glucose tolerance ©2014 Fred Hutchinson Cancer Research Center