1. Date of download: 6/21/2016 From: Adiposity of the Heart*, Revisited Ann Intern Med. 2006;144(7):517-524. doi:10.7326/0003-4819-144-7-200604040-00011 Concept of lipotoxicity.bottomLipotoxicity in humans originates from excessive release of free fatty acids from hypertrophied adipocytes in obese persons. Organ exposure to high levels of free fatty acids causes lipid droplets to accumulate within the cytosol of nonadipose tissues in proximity to mitochondria (white arrows, ). By-products of cytosolic triglyceride accumulation and of lipid metabolism may lead to organ dysfunction and failure. Figure Legend: Copyright © American College of Physicians. All rights reserved.American College of Physicians

2. Date of download: 6/21/2016 From: Adiposity of the Heart*, Revisited Ann Intern Med. 2006;144(7):517-524. doi:10.7326/0003-4819-144-7-200604040-00011 Myocardial lipotoxicity in the Zucker diabetic fatty rat.Top panel.white barslight gray barsdark gray barsBottom panel.Triglyceride content in the myocardium of Zucker diabetic fatty rats and lean controls at age 7 ( ) and 14 weeks ( ). The myocardial triglyceride accumulation is effectively prevented when thiazolidinedione therapy (troglitazone) is initiated at 7 weeks of age ( ). Functional changes in left ventricular fractional shortening is reduced over time as rats become fat and diabetic, but it is restored by triglyceride-lowering therapy with troglitazone. (Reproduced with permission from Proc Natl Acad Sci U S A. 2000;97:1784-9.) Figure Legend: Copyright © American College of Physicians. All rights reserved.American College of Physicians

3. Date of download: 6/21/2016 From: Adiposity of the Heart*, Revisited Ann Intern Med. 2006;144(7):517-524. doi:10.7326/0003-4819-144-7-200604040-00011 Myocardial-specific lipotoxicity.Top panel.Middle panel.gray barswhite barsBottom panel.Substantial cardiac hypertrophy in a murine model of myocardial specific triglyceride accumulation, developed by overexpressing a key enzyme involved in triglyceride synthesis, acetyl-CoA synthetase. Transgenic animals displayed substantially higher heart weight ( ) and heart-to-body weight ratio ( ). The hearts of the transgenic mice are characterized by elevated myocardial triglyceride content. Administration of leptin in the transgenic mice attenuates cardiac hypertrophy and normalizes myocardial triglyceride content. (Reproduced with permission from Proc Natl Acad Sci U S A. 2004;101:13624-9.) Figure Legend: Copyright © American College of Physicians. All rights reserved.American College of Physicians

4. Date of download: 6/21/2016 From: Adiposity of the Heart*, Revisited Ann Intern Med. 2006;144(7):517-524. doi:10.7326/0003-4819-144-7-200604040-00011 Magnetic resonance spectroscopy to evaluate skeletal muscle steatosis.leftABboxesmiddlerightHigh-resolution images ( ) of the calf muscle of a healthy patient ( ) and a patient with lipodystrophy ( ). The image was used to select a testing volume for spectroscopy within skeletal muscle away from adipose fat ( ). In a localized spectroscopy setup, only a signal from the selected volume is collected. Any other signal is destroyed and is not acquired. In these images, fat appears very bright, muscles are gray, and bones are black. Blood flowing into vessels is highlighted, and blood flowing out of vessels is black. The calf of a healthy control has a layer of adipose tissue and white marble fatty spots between muscle fibers. The lipodystrophic patient has no adipose fat present. The magnetic resonance spectrum ( ) from the tested volume contains a strong signal from tissue water and a very intense signal from triglyceride. Enlarged resonance ( ) of triglyceride region in a healthy patient and a patient with lipodystrophy. In the healthy patient, the fat spectrum contains 2 separate resonances: 1 from adipose fat between muscle fibers and 1 from triglyceride droplets within muscle cells. In the patient with lipodystrophy, the fat spectrum resonates exclusively from intramuscular triglyceride. Figure Legend: Copyright © American College of Physicians. All rights reserved.American College of Physicians

5. Date of download: 6/21/2016 From: Adiposity of the Heart*, Revisited Ann Intern Med. 2006;144(7):517-524. doi:10.7326/0003-4819-144-7-200604040-00011 Quantification of triglyceride within the human myocardium with magnetic resonance spectroscopy.leftboxrightIn this high-resolution, 4-chamber cardiac magnetic resonance image ( ), heart muscle appears dark gray; blood in myocardial chambers and epicardial and adipose fats are lighter. The volume for testing myocardial tissue ( ) was placed within an intraventricular septum and away from epicardial fat. Magnetic resonance spectrum ( ) with representative myocardial triglyceride resonance at 1.4 ppm. RA = right atria; LA = left atria; RV = right ventricle; LV = left ventricle. Figure Legend: Copyright © American College of Physicians. All rights reserved.American College of Physicians

6. Date of download: 6/21/2016 From: Adiposity of the Heart*, Revisited Ann Intern Med. 2006;144(7):517-524. doi:10.7326/0003-4819-144-7-200604040-00011 Myocardial triglyceride levels correlate positively with body mass index.In healthy persons without diabetes or hypertension, myocardial triglyceride levels are low and gradually increase as the body mass index increases. Figure Legend: Copyright © American College of Physicians. All rights reserved.American College of Physicians