Traditionally, obesity is considered an indirect cause of heart disease. Obese individuals
typically present with a number of traditional Framingham risk factors (hypertension,
dyslipidemia, and type 2 diabetes), predisposing them to heart attacks and subsequent heart
failure. However, an emerging body of basic research revisits a hypothesis that fat is a
direct cardiotoxin. Under healthy conditions, most triglyceride is stored in fatty tissue
(adipocytes) while the amount of triglyceride stored in non-adipocyte tissues (such as the
pancreas, the liver, skeletal muscle, and heart) is minimal and very tightly regulated. When
this regulation is disrupted, intracellular triglyceride accumulates excessively in these
organs ("steatosis") and has been implicated in activating adverse pathways which culminate
in irreversible cell death ("lipotoxicity"), leading to several well-recognized clinical
syndromes. These include non-alcoholic steatohepatitis (NASH), pancreatic beta-cell failure
in type 2 diabetes, and dilated cardiomyopathy.
It has been recently observed that angiotensin II receptor blockers (ARBs) in addition to
lowering blood pressure improve insulin sensitivity and decrease the risk for type 2
diabetes. This study will test the above theory in two study groups: Valsartan vs.
Hydrochlorothiazide. We hypothesize that in obese humans with elevated myocardial
triglycerides, blockade of the renin-angiotensin system (Valsartan group) will reduce
myocardial fat with improvement of insulin sensitivity and heart function.