Brown adipose tissue recruitment in-vivo and in-vitro
Sammanfattning: Brown adipose tissue recruitment was studied in the newborn hamster and in brown adipocyte precursor cell cultures.In the newborn hamster, the development of the thermogenic potential of brown adipose tissue was followed by estimating the amount of the uncoupling protein thermogenin by the binding of GDP to the mitochondria. Between the ages of 12 and 20 days, GDP Binding to isolated mitochondria rose sharply, indicating a dramatic increase in the thermogenic potential of brown adipose tissue during this period. This increase in thermogenic potential correlated well with morphological observations on the development of the tissue. It was concluded that in the perinatal hamster, brown adipose tissue recruits at a relatively late stage and that the recruited tissue probably contributes to the attainment of homeothermy in this species. The mechanisms which regulate this recruitment remain largely unknown.Brown adipocyte precursor cells, isolated as part of a stromal-vascular fraction derived from the brown adipose tissue of rat and mouse, were grown in culture. Various aspects of the recruitment process in brown adipose tissue were studied with these cell culture systems. Chronically raising cyclic-AMP levels with cholera toxin accelerated the differentation of rat brown adipocyte precursor cells, measured as enhanced levels of cytochrome £-oxidase and lipoprotein lipase mRNAs, and decreased levels of actin mRNA. A 35 kDa protein, of unknown identity, was also induced by this treatment.The cellular recruitment of thermogenin was studied in differentiating mouse brown adipocyte precursor cells. Thermogenin was expressed at low levels, if at all, in untreated cultures. Short-term norepinephrine treatment dramatically increased thermogenin mRNA and protein levels in the differentiating cells. Induction by norepinephrine was maximal in the period around confluence. Pharmacological characterization suggested that the norepinephrine signal was transduced mainly through ß-receptors (ß3-subtype), but transduction through aj-receptors was also involved. The newly synthesized thermogenin was incorporated into the mitochondria. Degradation studies suggested the existence of two pools of thermogenin.Thus, brown adipose tissue recruitment was studied in-vivo and invitro. The in-vitro studies on brown adipocyte cell cultures substantiate a central role for norepinephrine in the regulation of the recruitment process.
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