The Physiological Responses and Adaptation of Brown Adipose Tissue to Chronic Treatment With Beta3-Adrenergic Receptor Agonists
Background: Brown adipose tissue (BAT) is a type of fat in the body. It may prevent weight gain, improve insulin sensitivity, and reduce fatty liver. Researchers want to see if BAT helps the body burn energy.
Objective: To learn more about how BAT works to burn energy.
Eligibility: People ages 18-40 with a body mass index between 18 and 40
Design: Participants will be screened with: Medical history Physical exam Blood, urine, and heart tests Dietitian interview Participants will have an overnight baseline visit. This includes: Repeats of screening tests Exercise test Scans. For one scan, a radioactive substance is injected into the arm. FSIVGIT: An IV is inserted into veins in the right and left arms. Glucose and insulin are injected in one arm. Blood glucose and insulin levels are measured from the other. Metabolic suite: Participants stay 18 19 hours in a room that measures their metabolic rate. Monitors on the body measure heart rate, movement, and temperature. Optional fat biopsy: A small piece of tissue is removed with a needle. Participants will take 2-4 pills daily for 4 weeks. All women will take the drug mirabegron. Men will be randomly get either the drug or a placebo. All participants will have a visit after 2 weeks of the pills. They will repeat the screening tests. Participants will have an overnight visit 2 weeks later. They will repeat the baseline tests. Participants will keep food and medication diaries. Participants will have a follow-up visit 2 weeks after stopping the pills. This includes heart tests.
∙ In order to be eligible to participate in this study, an individual must meet all of the following criteria:
∙ Cohort 1: (complete)
• Female
• Age 18-40 years
• BMI 18.00-40.0 kg/m\^2
• Able to understand the research and willing to sign a written informed consent document
∙ Cohort 2: (complete)
• Male
• Age 18-40 years
• BMI 18.00-40.0 kg/m\^2
• Able to understand the research and willing to sign a written informed consent document
∙ Cohort 3:
• Female
• Age 18-40 years
• BMI 25.0-50.0 kg/m\^2 or BMI \> 18.5 kg/m\^2 with PCOS diagnosis
• Diagnosis of PCOS based on NIH Criteria; defined by the presence of both clinical and/or biochemical signs of hyperandrogenism and oligo- or chronic anovulation.
• Women of childbearing potential must agree to use a highly effective method of birth control, confirmed by the Investigator, for at least 3 months prior to the first study visit and continuing throughout the study duration.
• a. Highly effective methods of birth control include:
• i. Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, or transdermal
• ii. Progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable, or implantable
• iii. Intrauterine device
• iv. Intrauterine hormone-releasing system
• v. Bilateral tubal occlusion
• vi. Sexual abstinence, i.e., refraining from heterosexual intercourse (the reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the participant)
• vii. Vasectomized sexual partner (provided that partner is the sole sexual partner of the study participant and that the vasectomized partner has received medical assessment of the surgical success)
• b. Women not of childbearing potential are defined as women who are either permanently sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy) or who are postmenopausal. Women will be considered postmenopausal if they have been amenorrhoeic for \>=12 months prior to the planned date of enrollment without an alternative medical cause.
• Insulin resistance defined by either
‣ HOMA-IR score \> 5.9 OR
⁃ HOMA-IR score \> 2.8 and \<5.9, with HDL \<51 mg/dL OR
⁃ Fasting Insulin \> 10.6 microU/mL
• Able to understand the research and willing to sign a written informed consent document