Race, Menopause and Metabolism After Exercise and Diet

The purpose of this study is to test the hypotheses that there are ethnic and genetic differences in the mechanisms and magnitude by which hypocaloric weight loss and aerobic exercise affect body composition, glucose, lipid, muscle and adipose tissue metabolism in overweight, insulin resistant postmenopausal women. This will be tested in a trial comparing the effects of weight loss vs. aerobic exercise plus weight loss on glucose, lipid, fat and muscle metabolism in overweight African American and Caucasian postmenopausal women.

The findings of this study will also determine whether there are racial differences in the whole body and cellular mechanisms by which aerobic exercise training and weight loss affect glucose, lipid, fat and muscle metabolism in African-American vs. Caucasian postmenopausal women. The results also may provide a rationale for targeting specific populations of women who might improve glucose, lipid, fat and muscle metabolism more from the addition of exercise to dietary restriction than weight loss alone to reduce their risk for type 2 diabetes and cardiovascular disease. The study protocol consists of the following phases: Phase 1-Recruitment and screening. Phase 2-Weight and dietary stabilization for 4-6 weeks, where participants are taught the principles of the American Heart Association "Heart Healthy" diet and provided food to consume prior to testing. Phase 3-Participants will undergo research testing including glucose clamp and fat biopsy. Phase 4-Participants select either weight loss only, or exercise plus weight loss. The behavior diet modification weight loss sessions are held by a registered dietitian for 1 hour once a week for 6-9 months where the recommended caloric intake for each participant is adjusted by the dietitian to elicit a weight loss of approximately 0.2-0.4 kg per week. In addition to the weight loss sessions, participants who select the aerobic exercise plus weight loss intervention will exercise at the Baltimore Geriatric Research Education and Clinical Center (GRECC) exercise facility 3 times a week for 6-9 months using treadmills and other aerobic exercise equipment. Exercise sessions begin at low levels of VO2max (maximal oxygen consumption) and progress in duration and intensity until the participant is able to exercise at more than 75% VO2max for 45 minutes. Phase 5-Following the 6-9 months of long-term weight loss or exercise plus weight loss, all participants will undergo long-term metabolic testing.

Weight loss sessions are held by a registered dietitian for 1 hour once a week for 6-9 months; recommended caloric intake to elicit a weight loss of approximately 0.2-0.4 kg per week

Treadmills and other aerobic exercise equipment 3 times a week for 6-9 months, beginning at low levels of VO2max and progressing in duration and intensity to more than 75% VO2max for 45 minutes

Inclusion Criteria: Female 45-80 yrs of age Non-smoking for one year BMI greater than 25 kg/m2 and less than 50 kg/m2 Menopause over 1 year Caucasian or African American ethnicity Exclusion Criteria: Both groups Currently being treated for active cancer Type 1 diabetes; insulin treatment; poorly controlled (fasting blood sugar over 160 mg/dl) Allergic to lidocaine or heparin Untreated dyslipidemia, receiving triglyceride-lowering meds Other systemic disorders that are not medically treated and stable Taking beta-blockers, oral steroids, warfarin or any other medications interfering with fat/muscle metabolism that may not be safely discontinued temporarily for specific procedures (i.e. for 72 hours prior) Abnormal liver or renal function; chronic pulmonary disease (on supplemental oxygen); anemia MMSE (Mini-Mental State Examination) below 24, dementia or unstable clinical depression by exam Women of ethnicity other than Caucasian or African American Symptomatic heart disease, coronary artery disease, congestive heart failure, or uncontrolled hypertension unless medically stabilized Abnormal response to exercise test (chest pain, significant arrhythmias, extreme shortness of breath, cyanosis, exercising blood pressure above 240/120mm Hg, or other contraindications to exercise) Exercise plus weight loss group only Medical history of CVD (cardiovascular disease) with symptoms limiting ability to exercise Physical impairment limiting normal activity Aerobically trained with VO2max greater than 2 SD (standard deviation) above age-adjusted mean

Berman DM, Rodrigues LM, Nicklas BJ, Ryan AS, Dennis KE, Goldberg AP. Racial disparities in metabolism, central obesity, and sex hormone-binding globulin in postmenopausal women. J Clin Endocrinol Metab. 2001 Jan;86(1):97-103. doi: 10.1210/jcem.86.1.7147.

Ryan AS, Nicklas BJ, Berman DM. Racial differences in insulin resistance and mid-thigh fat deposition in postmenopausal women. Obes Res. 2002 May;10(5):336-44. doi: 10.1038/oby.2002.47.

Nicklas BJ, Dennis KE, Berman DM, Sorkin J, Ryan AS, Goldberg AP. Lifestyle intervention of hypocaloric dieting and walking reduces abdominal obesity and improves coronary heart disease risk factors in obese, postmenopausal, African-American and Caucasian women. J Gerontol A Biol Sci Med Sci. 2003 Feb;58(2):181-9. doi: 10.1093/gerona/58.2.m181.

Ryan AS, Nicklas BJ, Berman DM. Aerobic exercise is necessary to improve glucose utilization with moderate weight loss in women. Obesity (Silver Spring). 2006 Jun;14(6):1064-72. doi: 10.1038/oby.2006.122.

Ryan AS, Serra MC, Goldberg AP. Metabolic Benefits of Prior Weight Loss with and without Exercise on Subsequent 6-Month Weight Regain. Obesity (Silver Spring). 2018 Jan;26(1):37-44. doi: 10.1002/oby.22032. Epub 2017 Oct 25.

Ortmeyer HK, Goldberg AP, Ryan AS. Exercise with weight loss improves adipose tissue and skeletal muscle markers of fatty acid metabolism in postmenopausal women. Obesity (Silver Spring). 2017 Jul;25(7):1246-1253. doi: 10.1002/oby.21877. Epub 2017 May 26.

Ge S, Ryan AS. Zinc-alpha2-glycoprotein expression in adipose tissue of obese postmenopausal women before and after weight loss and exercise + weight loss. Metabolism. 2014 Aug;63(8):995-9. doi: 10.1016/j.metabol.2014.04.013. Epub 2014 May 4.

Ryan AS, Ge S, Blumenthal JB, Serra MC, Prior SJ, Goldberg AP. Aerobic exercise and weight loss reduce vascular markers of inflammation and improve insulin sensitivity in obese women. J Am Geriatr Soc. 2014 Apr;62(4):607-14. doi: 10.1111/jgs.12749. Epub 2014 Mar 17.

Prior SJ, Blumenthal JB, Katzel LI, Goldberg AP, Ryan AS. Increased skeletal muscle capillarization after aerobic exercise training and weight loss improves insulin sensitivity in adults with IGT. Diabetes Care. 2014 May;37(5):1469-75. doi: 10.2337/dc13-2358. Epub 2014 Mar 4.

Yang RZ, Blumenthal JB, Glynn NM, Lee MJ, Goldberg AP, Gong DW, Ryan AS. Decrease of circulating SAA is correlated with reduction of abdominal SAA secretion during weight loss. Obesity (Silver Spring). 2014 Apr;22(4):1085-90. doi: 10.1002/oby.20657. Epub 2013 Dec 6.

Ryan AS, Li G, Blumenthal JB, Ortmeyer HK. Aerobic exercise + weight loss decreases skeletal muscle myostatin expression and improves insulin sensitivity in older adults. Obesity (Silver Spring). 2013 Jul;21(7):1350-6. doi: 10.1002/oby.20216. Epub 2013 May 19.