We propose a series of novel studies directed at establishing the effects of increased body fat in healthy individuals. We will determine the distribution patterns of increased body fat and how both increased body fat and fat distribution may affect blood pressure, as well as neural, vascular and inflammatory mechanisms which have been implicated in cardiac and vascular disease. We will study sedentary subjects with and without a family history of hypertension. These subjects will undergo a program of overfeeding with the objective of inducing a 2 kg fat gain. We will study these individuals before and after the 4-week fat gain program and subsequently after an 8-week period of weight loss and restoration of normal weight. Measurements will also be compared to those in a matched control group with and without a family history of hypertension, who continue their normal diet. We will test the following hypotheses: 1) Individuals with a family history of hypertension will gain more visceral and upper body fat and have greater blood pressure increases with overfeeding, compared to those without such a family history. 2) For all overfed subjects, increases in blood pressure, sympathetic activity and insulin resistance with fat gain will be most marked in those individuals with a predominantly upper body and visceral fat accumulation. 3) Upper body and visceral fat gain will also be associated with greater impairment in baroreflex sensitivity, endothelial function and chemoreflex function, and an increased likelihood of abnormalities during sleep, including higher nocturnal blood pressures and sleep disordered breathing. 4) Fat gain, particularly upper body and visceral, will be accompanied by enhanced production of inflammatory mediators linked to cardiovascular risk, including adhesion molecules and C-reactive protein. 5) The above changes will resolve with subsequent loss of weight and restoration of normal body fat. These studies build on established programs, one addressing obesity, sleep disordered breathing and cardiovascular disease directed by Dr. Somers, and the other examining mechanisms regulating body fat in humans, directed by Dr. Jensen. This integrated state-of-the-art approach will enable important and novel insights into interactions between fat gain and neural, vascular, and inflammatory cardiovascular disease mechanisms.
| Covassin, Naima; Sert-Kuniyoshi, Fatima H; Singh, Prachi et al. (2018) Experimental Weight Gain Increases Ambulatory Blood Pressure in Healthy Subjects: Implications of Visceral Fat Accumulation. Mayo Clin Proc 93:618-626 |
| Singh, P; Sharma, P; Sahakyan, K R et al. (2016) Differential effects of leptin on adiponectin expression with weight gain versus obesity. Int J Obes (Lond) 40:266-74 |
| Calvin, Andrew D; Somers, Virend K; Johnson, Bruce D et al. (2014) Left atrial size, chemosensitivity, and central sleep apnea in heart failure. Chest 146:96-103 |
| Mansukhani, Meghna Prabhdas; Calvin, Andrew Donald; Kolla, Bhanu Prakash et al. (2013) The association between atrial fibrillation and stroke in patients with obstructive sleep apnea: a population-based case-control study. Sleep Med 14:243-6 |
| Singh, Prachi; Somers, Virend K; Romero-Corral, Abel et al. (2012) Effects of weight gain and weight loss on regional fat distribution. Am J Clin Nutr 96:229-33 |
| Singh, Prachi; Peterson, Timothy E; Sert-Kuniyoshi, Fatima H et al. (2012) Leptin signaling in adipose tissue: role in lipid accumulation and weight gain. Circ Res 111:599-603 |
| Albuquerque, Felipe N; Calvin, Andrew D; Sert Kuniyoshi, Fatima H et al. (2012) Sleep-disordered breathing and excessive daytime sleepiness in patients with atrial fibrillation. Chest 141:967-973 |
| Adachi, Taro; Sert-Kuniyoshi, Fatima H; Calvin, Andrew D et al. (2011) Effect of weight gain on cardiac autonomic control during wakefulness and sleep. Hypertension 57:723-30 |
| Singh, Prachi; Peterson, Timothy E; Sert-Kuniyoshi, Fatima H et al. (2011) Leptin upregulates caveolin-1 expression: implications for development of atherosclerosis. Atherosclerosis 217:499-502 |
| Calvin, Andrew D; Somers, Virend K; van der Walt, Christelle et al. (2011) Relation of natriuretic peptide concentrations to central sleep apnea in patients with heart failure. Chest 140:1517-1523 |
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