Temperature, brown adipose tissue, and skeletal phenotype

Bone size, shape, and strength vary in humans living at different latitudes. In this project we ask whether temperature contributes to this variation.  We are particularly interested in how cold exposure and brown fat (a special kind of fat that generates heat) affect bone mass, since humans living in cold climates tend to exhibit accelerated age-related bone loss. Cold exposure increases sympathetic tone (epinephrine or the “fight or flight” response), which can cause bone resorption. Brown fat might protect against this bone loss by increasing body temperature and decreasing sympathetic tone. Recent studies show that adult humans retain brown fat into adulthood and that brown fat is positively associated with higher bone mineral density and bone mass in humans. We hypothesize that brown fat represents a link between temperature, exercise and bone mass that contributes to worldwide patterns of human skeletal variation. Our approach to testing this hypothesis combines controlled experiments in animal models and comparative studies in human skeletal remains.

Key findings:

• Mice raised in the cold have lower trabecular bone volume in the distal femur (shown at right) and cortical bone mass in the midshaft femur vs. mice raised at higher temperatures
• Cold exposure increases BAT activity, but this alone does not protect against bone loss
• During cold exposure, blocking sympathetic tone with a drug called propranolol decreases the amount of heat produced in brown fat, but also completely protects against bone loss
• These findings support our hypothesis that sympathetic activation is a major cause of accelerated bone loss in cold-dwelling humans
• We are currently studying whether diet and exercise change the effects of temperature on the skeleton

Isotope fractionation in mammalian tissue

Stable isotopes recovered from the mineral and organic components of bone are often used to reconstruct diet, trophic level, life history patterns, environmental parameters, and migration patterns in the archeological and paleontological record. Critically, the accuracy of such reconstructions relies on a detailed and comprehensive understanding of the cycling of isotopes in organisms and compositional variability in depositional tissues due to discrete routing or differential fractionation. If the assumptions of isotope fractionation in various tissues are incorrect, then subsequent ecological reconstructions are also likely to be incorrect. Despite this recognition, few studies have systematically examined the relationship between dietary nitrogen and carbon and dental/skeletal nitrogen and carbon experimentally. In this project we are exploring nitrogen and carbon fractionation in the tissues of mice whose dietary intake is isotopically characterized, with known values for protein, carbohydrate and lipid components. The goal is to measure how these isotopes are incorporated into mineralized and non-mineralized body tissues through several generations. These data will improve isotope-based dietary reconstructions in the fossil and archeological record.