Supplementary prenatal copper increases plasma triiodothyronine and brown adipose tissue uncoupling protein-1 gene expression but depresses thermogenesis in newborn lambs

Objective: We tested the hypothesis that increasing dietary copper (Cu) to gravid ewes would enhance brown adipose tissue (BAT) thermogenesis in their offspring. Methods: Twin-bearing ewes were assigned on d 70 of gestation to diets containing 3, 10, or 20 ppm dietary Cu (n = 8 per group). Twin lambs were assigned at birth to a cold (6℃) or warm (28℃) environmental chamber for 48 h. Blood was collected from ewes and from lambs and perirenal BAT was collected after 48 h in the environmental chambers. Results: Prenatal Cu exposure increased ewe plasma triiodothyronine (T₃) and thyroxine concentration (T₄) (p<0.01) but prenatal Cu exposure had no effect on lamb plasma concentrations of T₃, T₄, glucose, or nonesterified fatty acid concentration (p≥0.08). The high level of prenatal Cu exposure depressed 48-h rectal temperature (p = 0.03). Cold exposure decreased BAT norepinephrine (NE) and increased BAT dopamine (p≤0.01), but prenatal Cu exposure had no effect on BAT cytochrome C oxidase activity or BAT NE or dopamine (p≥0.07). However, BAT of lambs from high-Cu ewes maintained higher uncoupling protein-1 (UCP1) gene expression than BAT of lambs from low- and medium-Cu ewes following warm or cold exposure in environmental chambers (p = 0.02). Cold exposure caused near depletion of BAT lipid by 48 h (p<0.001), increased BAT cytochrome c oxidase activity (p<0.01), and depressed plasma fatty acid concentrations (p<0.001). Conclusion: Although prenatal Cu exposure increased BAT UCP1 expression during warm and cold exposure, prenatal cold Cu exposure depressed 48-h rectal temperature. Cold exposure decreased BAT lipid content by over 80% and decreased lamb plasma fatty acid concentration by over 40%, indicating that fuel reserves for thermogenesis were nearly depleted by 48 h of cold exposure.