Fat Gain and Cardiovascular Disease Mechanisms
Fat Gain and Cardiovascular Disease Mechanisms
Understanding the mechanisms of obesity-induced hypertension is important both for prevention
 and therapy. Studies of patients with established obesity have provided valuable information
 on pathophysiologic links between obesity and both blood pressure and cardiovascular risk.
 However, these studies are necessarily limited by the heterogeneity of obesity-associated
 disease so that the relative contribution of obesity or hypertension or other co-existing
 diseases to specific regulatory abnormalities is often not clear. Clarification of whether
 any abnormalities associated with increased cardiovascular risk were present before or after
 the development of obesity has also been problematic.

 We therefore propose a series of novel studies directed at establishing the effects of
 increased body fat in otherwise healthy individuals. We will determine the distribution
 patterns of increased body fat and how both increased body fat and fat distribution relate to
 changes in blood pressure, and in neural, endothelial and inflammatory mechanisms which have
 been implicated in the development and progression of cardiac and vascular disease.

 We will study non-obese subjects with and without a family history of hypertension. These
 subjects will undergo an eight-week program of overfeeding with the objective of inducing a 4
 kg fat gain. We will determine the nature of fat distribution in these individuals after the
 fat gain program and subsequently after an eight-week period of weight loss and restoration
 of normal body weight. Measurements will be compared to those obtained in a matched control
 group with and without a family history of hypertension, who will continue their normal
 diets. We will test the following hypotheses:

 -  Individuals with a family history of hypertension will gain more visceral fat and upper
 body subcutaneous fat and will have greater blood pressure increases with overfeeding-
 compared with those without such a family history.

 -  For all overfed subjects, increases in blood pressure and insulin resistance with fat
 gain will be most marked in those individuals with a predominantly upper body and
 visceral fat accumulation.

 -  Upper body and visceral fat gain will also be associated with greater impairment in
 cardiovascular function, higher nocturnal blood pressures and an increased likelihood of
 sleep disordered breathing.
Inclusion Criteria:

 -  We will enroll up to 180 subject in order to fulfill screening requirements and have
 complete studies in 120 total (60 with and 60 without family history hypertension).

 -  Gender: Male and female.

 -  Ages: 18 to 40 (inclusive).

 Exclusion Criteria:

 -  Body-mass index > 33 kg/m2

 -  Tobacco smoking or chewing

 -  Shift worker

 -  Any diseases

 -  Any prescription medications (except, oral contraceptives are permitted)