Obesity is more prevalent in women than in men, a fact that may be related to fluctuations in reproductive hormones across a woman's lifespan. Menopause is associated with increased body weight and abdominal adiposity independent of aging. Diet and activity factors are implicated in the weight gain at menopause; however, the role of these factors is not well-understood. Our original study tested the hypotheses that 1) menopause-associated increases in visceral fat are hormone-related, 2) increased body fat at menopause is due to decreased energy expenditure and increased energy intake, and 3) African-American and Caucasian women have differential body fat changes at menopause. We began testing these hypotheses in a biethnic cohort of 161 middle-aged, premenopausal women recruited in 1998-99. To date, we have completed 3- year follow-up on 132 women and 4-year follow-up on approximately 80 women (the remainder are in progress). As only 34 women went through menopause by the 3-year follow-up, the first objective of this renewal is to continue to follow our initial cohort for an additional 3 years, by which time most subjects should be postmenopausal with a mean age of 54 years. This is necessary to address our major hypotheses related to the impact of menopause per se on body composition and energy balance. The second objective of the current proposal is to test the hypothesis that decreased leptin pulsatile secretion and subsequent changes in sympathetic nervous system (SNS) activity are a mechanism by which menopause may increase body weight. Specifically, we hypothesize that, 1) in relation to their altered LH secretion, postmenopausal women will have lower 24-hr leptin pulsatile secretion, 2) African-American women will have higher 24-hr leptin pulsatile secretion than Caucasians, 3) Decreased 24-hr serum leptin secretion will be associated with decreased leptin secretion and leptin mRNA in adipose tissue, 4) Subjects with lower 24-hr leptin secretion will exhibit lower SNS activity. To accomplish this objective, we will recruit new cohorts of premenopausal and postmenopausal women for 24-hr hormone pulsatility studies. Overall, continuing to follow the longitudinal cohort for up to 7 years provides a unique and valuable opportunity to examine the natural history of body composition changes during the menopause transition, while the new studies will provide novel mechanistic information about the role of hormonal changes at menopause on obesity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK050736-05
Application #
6727859
Study Section
Nutrition Study Section (NTN)
Program Officer
Staten, Myrlene A
Project Start
1997-09-01
Project End
2006-11-30
Budget Start
2004-02-15
Budget End
2004-11-30
Support Year
5
Fiscal Year
2004
Total Cost
$209,727
Indirect Cost
Name
Lsu Pennington Biomedical Research Center
Department
Type
Organized Research Units
DUNS #
611012324
City
Baton Rouge
State
LA
Country
United States
Zip Code
70808
Lovejoy, J C; Champagne, C M; de Jonge, L et al. (2008) Increased visceral fat and decreased energy expenditure during the menopausal transition. Int J Obes (Lond) 32:949-58
Solinas, G; Summermatter, S; Mainieri, D et al. (2006) Corticotropin-releasing hormone directly stimulates thermogenesis in skeletal muscle possibly through substrate cycling between de novo lipogenesis and lipid oxidation. Endocrinology 147:31-8
Lara-Castro, Cristina; Hunter, Gary R; Lovejoy, Jennifer C et al. (2005) Apolipoprotein A-II polymorphism and visceral adiposity in African-American and white women. Obes Res 13:507-12
Lara-Castro, Cristina; Hunter, Gary R; Lovejoy, Jennifer C et al. (2005) Association of the intestinal fatty acid-binding protein Ala54Thr polymorphism and abdominal adipose tissue in African-American and Caucasian women. J Clin Endocrinol Metab 90:1196-201
Lovejoy, Jennifer C (2003) The menopause and obesity. Prim Care 30:317-25
Lovejoy, J C; Smith, S R; Rood, J C (2001) Comparison of regional fat distribution and health risk factors in middle-aged white and African American women: The Healthy Transitions Study. Obes Res 9:10-6
Lovejoy, J C; Champagne, C M; Smith, S R et al. (2001) Ethnic differences in dietary intakes, physical activity, and energy expenditure in middle-aged, premenopausal women: the Healthy Transitions Study. Am J Clin Nutr 74:90-5
Womble, L G; Williamson, D A; Martin, C K et al. (2001) Psychosocial variables associated with binge eating in obese males and females. Int J Eat Disord 30:217-21