BATokines as Biomarkers of Brown Fat in Humans

Brown adipose tissue (BAT) burns excess calories to produce heat in response to environmental cold. Rapidly growing evidence from rodent and human studies suggests that the presence and activation of brown fat are far more beneficial for whole body metabolism and cardiometabolic health than previously appreciated. Despite the clear associations between brown fat and metabolic health, we lack both: cost-effective means of detecting brown fat in humans as well as comprehensive insights into how brown fat facilitates metabolism on a molecular level in humans. Emerging evidence suggests that the benefits of brown fat activation are mediated, at least in part, by secretion of specific molecules into the bloodstream which signal to metabolically active organs such as skeletal muscle, liver and brain. A number of these so-called brown adipokines (or BATokines) have now been discovered in mice and shown to positively impact glucose homeostasis, liver and muscle function. Human deep-neck brown fat biopsies reveal that \>1000 molecules could potentially be secreted from brown fat, and \>400 are released by human brown fat cells in a dish, representing a major opportunity for discovery of high translational value. Here, we aim to identify a screen of first potential blood biomarkers of brown fat in healthy young humans. This will be achieved by analyzing plasma proteins in subjects with 'inactive brown fat' (warm) and 'activated brown fat' (3-hr cold exposure, cooling vests) using high-throughput technologies (SOMAscan and O-link) to identify temperature-sensitive brown fat-enriched molecules. This preliminary data will guide a larger follow up study in which we envision studying lean and obese (insulin sensitive and insulin resistant) subjects of various age groups and race/ethnicity. Human BATokines identified here will become primary targets for manipulation in experimental animals to assess their therapeutic potential against obesity, T2D, and associated diseases. Additionally, since current methods of brown fat detection in human rely on deep neck biopsies or costly 18-FDG-PET/CT scans, identification of blood biomarkers of brown fat would offer a cost-effective and non-invasive alternative for prediction of metabolic health in humans.

Inclusion Criteria: * Age between 18 and 28 * BMI \>19 and \< 25 Exclusion Criteria: * Diabetes type I or II (self-report) * Diagnosis of thyroid disease (including goiter, hyperthyroidism, hypothyroidism, thyroiditis) (self-report) * Diagnosis with cancer including skin cancer (self-report) * Diagnosis or evidence of Raynaud's Syndrome or systemic sclerosis (self report) * Previously or currently diagnosed with SARS-Cov-2 infection/COVID-19 (secondary to unknown immune responses) * Any vaccine administration within two weeks preceding the study procedure * Currently pregnant * Currently taking any prescribed medication other than oral contraceptives * Treatments for weight loss or any other supplements that may alter weight or metabolism are not acceptable (vitamins are acceptable) * Has consumed nicotine (smoking, inhaling, ingesting) within the last within the last 6 months * Has used illicit drugs within the last 6 months * Any medical, psychological, or social condition that, in opinion of principle investigators, would jeopardize the health or well-being of the participant during the study procedure or integrity of the data