Abstract
ObjectiveWe tested the hypothesis that increasing dietary copper (Cu) to gravid ewes would enhance brown adipose tissue (BAT) thermogenesis in their offspring.MethodsTwin-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°C) or warm (28°C) 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.ResultsPrenatal 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).ConclusionAlthough 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.
Highlights
One-half of maximal thermogenic response to cold stress in newborn lambs is derived from nonshivering thermogenesis of brown adipose tissue (BAT) [1]
Brown adipose tissue is highly innervated by the sympathetic nervous system [2] which, during cold exposure, releases norepinephrine (NE) to activate BAT thermogenesis by stimulating fatty acid oxidation and uncoupling protein-1 (UCP1) gene expression
Because several Cu-dependent enzyme systems are involved in regulating BAT thermogenesis, including c oxidase (COX) and dopamine-β-hydroxylase, we hypothesized that increas
Summary
One-half of maximal thermogenic response to cold stress in newborn lambs is derived from nonshivering thermogenesis of brown adipose tissue (BAT) [1]. The ability of BAT to generate heat is due to the presence of uncoupling protein-1 (UCP1), found only in BAT mitochondria. When stimulated by cold exposure, UCP1 acts to uncouple oxidative phosphorylation from fatty acid oxidation, thereby causing BAT mitochondria to generate heat rather than ATP. Brown adipose tissue is highly innervated by the sympathetic nervous system [2] which, during cold exposure, releases norepinephrine (NE) to activate BAT thermogenesis by stimulating fatty acid oxidation and UCP1 gene expression. NE activates type II thyroxine 5’deiodinase in BAT to convert thyroxine (T4) to the more active thyroid hormone triiodothyronine (T3) [3].
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