Acute Exercise on Brain Insulin Sensitivity

Obesity, hypertension, high blood glucose (e.g. prediabetes/type 2 diabetes), and physical inactivity is thought to worsen brain insulin resistance and reduce cerebral blood flow. This suggests lifestyle approaches may be necessary to counteract declines in brain health. Regular aerobic exercise decreases Alzheimer's Disease (AD) risk, in part, through changes in brain structure and function. Moreover, exercise-related structural changes in the brain, namely increased hippocampal volume, is linked to improved memory. However, there is limited data available on how exercise impacts brain insulin resistance in aging. It is also unclear if one bout of exercise may help improve brain insulin responses to insulin before fitness gains or weight loss in people at risk for dementia, type 2 diabetes and cardiovascular disease. Because single bouts of exercise are established to improve metabolic and vascular insulin sensitivity in people with obesity, the investigators anticipate exercise to raise brain insulin sensitivity in relation to cognition and cardiometabolic health.

Inclusion criteria

• Male or female >/=40 and </=80 years old.
• Has a body mass index >/=25 and </=45 kg/m2.
• Physical Activity (<150 min of moderate/high intensity exercise per week)

Exclusion criteria

• Subjects who have not been weight stable (>2 kg weight change in past 3 months)
• Subjects who are smokers or who have quit smoking <1 years ago
• Subjects with abnormal estimated glomerular filtration rate (eGFR).
• Hypertriglyceridemic (>400 mg/dl) and hypercholesterolemic (>260 mg/dl) subjects
• Hypertensive (>160/100 mmHg)
• Subjects with a history of significant metabolic, cardiac, congestive heart failure, cerebrovascular, hematological, pulmonary, gastrointestinal, liver, renal, or endocrine disease or cancer that in the investigator's opinion would interfere with or alter the outcome measures or impact subject safety.
• Pregnant (as evidenced by positive urine pregnancy test) or nursing women
• Subjects with contraindications to participation in an exercise
• Current Pregnancy
• Currently taking active weight suppression medication (e.g. phentermine, orlistat, lorcaserin, naltrexone-bupropion in combination, liraglutide, benzphetamine, diethylpropion, phendimetrazine)
• Subjects currently taking medications that affect heart rate and rhythm (i.e. Ca++ channel blockers, nitrates, alpha- or beta-blockers).
• Known contraindications for MRI imaging