The susceptibility to gain weight is highly variable even when caloric intake and physical activity are well controlled. Because basal metabolic rate (BMR) represents approximately 70% of total daily energy expenditure (TDEE), even a small difference in BMR can affect daily energy balance, thereby increasing the susceptibility for gaining weight. Our preliminary data indicate that high-normal growth hormone (GH) secretion is associated with resistance to weight-gain in rats when overfed and greater weight-loss in humans when underfed. Given that GH influences many of the key metabolic processes that contribute to BMR, we hypothesize that persons with high-normal GH will be resistant to weight gain because of a high BMR, resulting from accelerated rates of these processes. We will measure basal 24h GH secretion and BMR in 106 non-obese men and women. We will also measure protein synthesis, proteolysis, triglyceride/fatty acid cycling (all measured using stable isotope tracer methods) to determine the relationships among these processes, BMR, and GH [Specific Aim 1]. Subjects identified as having """"""""low-normal"""""""" (<1.5 ug/L) and """"""""high-normal"""""""" (>3 ug/L) 24h GH will then be admitted to the hospital for a 2 wk overfeeding protocol (approximately 2000 kcal/d >TDEE - with restricted physical activity), immediately followed by a 4 wk caloric restriction protocol (approximately 750 kcal/d

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK071955-02
Application #
7117314
Study Section
Integrative Physiology of Obesity and Diabetes Study Section (IPOD)
Program Officer
Miles, Carolyn
Project Start
2005-09-01
Project End
2010-08-31
Budget Start
2006-09-01
Budget End
2007-08-31
Support Year
2
Fiscal Year
2006
Total Cost
$413,639
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Miscellaneous
Type
Other Domestic Higher Education
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Cornford, Andrea S; Hinko, Alexander; Nelson, Rachael K et al. (2013) Rapid development of systemic insulin resistance with overeating is not accompanied by robust changes in skeletal muscle glucose and lipid metabolism. Appl Physiol Nutr Metab 38:512-9
Cornford, Andrea S; Barkan, Ariel L; Hinko, Alexander et al. (2012) Suppression in growth hormone during overeating ameliorates the increase in insulin resistance and cardiovascular disease risk. Am J Physiol Endocrinol Metab 303:E1264-72
Li, Minghua; Paran, Christopher; Wolins, Nathan E et al. (2011) High muscle lipid content in obesity is not due to enhanced activation of key triglyceride esterification enzymes or the suppression of lipolytic proteins. Am J Physiol Endocrinol Metab 300:E699-707
Newsom, Sean A; Schenk, Simon; Li, Minghua et al. (2011) High fatty acid availability after exercise alters the regulation of muscle lipid metabolism. Metabolism 60:852-9
Cornford, Andrea S; Barkan, Ariel L; Horowitz, Jeffrey F (2011) Rapid suppression of growth hormone concentration by overeating: potential mediation by hyperinsulinemia. J Clin Endocrinol Metab 96:824-30
Ribeiro-Oliveira Jr, Antônio; Faje, Alexander T; Barkan, Ariel L (2011) Limited utility of oral glucose tolerance test in biochemically active acromegaly. Eur J Endocrinol 164:17-22
Kraftson, Andrew; Barkan, Ariel (2010) Quantification of day-to-day variability in growth hormone levels in acromegaly. Pituitary 13:351-4
Faje, Alexander T; Barkan, Ariel L (2010) Basal, but not pulsatile, growth hormone secretion determines the ambient circulating levels of insulin-like growth factor-I. J Clin Endocrinol Metab 95:2486-91
Knuth, Nicolas D; Shrivastava, Cara R; Horowitz, Jeffrey F (2009) Reducing dietary fat from a meal increases the bioavailability of exogenous carbohydrate without altering plasma glucose concentration. J Appl Physiol 106:122-9
Surya, Sowmya; Horowitz, Jeffrey F; Goldenberg, Naila et al. (2009) The pattern of growth hormone delivery to peripheral tissues determines insulin-like growth factor-1 and lipolytic responses in obese subjects. J Clin Endocrinol Metab 94:2828-34

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