Jan Nedergaard

Brown adipose tissue: molecular mechanisms controlling activity and thermogenesis

Publisher Summary This chapter describes brown adipose tissue (BAT), its molecular mechanisms controlling activity, and thermogenesis. The naturally occurring mediator of thermogenesis in the tissue, noradrenaline (NA), can interact with both alpha adrenergic and beta adrenergic receptors. However, the major fraction of the heat production of isolated cells seems to derive from beta-1 adrenergic processes. Thermogenesis in the brown fat cell is activated in vivo through nervous stimulation, and not through blood-borne agents. It is believed that the brown adipocytes possess dual innervation, both through the intercostal nerve fibers and fibers entering the tissue with the blood vessels, but innervating not only the vessels themselves, but also the adipocytes. It is clear from the studies of molecular mechanisms of BAT that an intact nervous supply and a euthyroid state are essential for recruitment of BAT. It is possible that catecholamines in themselves have a stimulatory effect on recruitment, but this has to be demonstrated convincingly. It should be remembered that sympathetic nerves can contain hormones other than catecholamines, for example co-stored peptide hormones can be present and can disappear as a result of sympathectomy. It is also important to remember the paradox of the hibernators, who seem to be able to recruit BAT without activating the tissue. Thus, chronic catecholamine stimulation does not seem to be the only pathway of recruitment.

Enzyme-linked immunosorbent assay (Elisa) studies of the interaction between mammalian and avian anti-thermogenin antibodies and brown-adipose-tissue mitochondria from different species

Three different antibody preparations, rabbit anti-hamster and rabbit anti-rat thermogenin sera and chicken anti-rat thermogenin IgG, were tested for cross-reactivity towards isolated thermogenin and BAT mitochondria from different mammalian species using an ELISA-technique. It was found that the antibody preparations readily cross-reacted with different species, but that the affinity of the antibody preparations was greater towards the homologous species than the other species. The reactivity of an antibody preparation towards mitochondria from different tissues from the homologous species was also tested, and the exclusive occurrence of thermogenin in BAT could be confirmed.

AN ATTEMPT TO DIFFERENTIATE BETWEEN α- AND β-ADRENERGIC RESPIRATORY RESPONSES IN HAMSTER BROWN FAT CELLS

Publisher Summary This chapter discusses the roles of α- and β-adrenergic stimulation for the regulation of heat production. In an experiment described in the chapter, brown fat cells were isolated from some adult golden hamsters, which had been living at an ambient temperature of 21°C, by the use of the collagenase digestion procedure. Adrenergic effects on nerve vesicles within the tissue, and the possible influence of presynaptic receptors, are minimized by the use of isolated cells. α-receptors may affect the oxygen consumption or heat production of the isolated cells. The clarification of the biochemical pathways for α-adrenergic stimulation of brown fat cells remains a challenging problem.