Regulation of brown adipose tissue by stress and sex

Due to the increasing incidence of obesity, more means of treating obesity are necessary. Brown adipose tissue (BAT) is a potential target tissue via which obesity can be treated due to its unique ability to use energy to produce heat. Not much is known however about the mechanisms via which BAT activity is maintained under physiological circumstances. This thesis describes the influence of two different types of hormones on BAT activity: stress hormones and sex hormone steroids. The hypothalamic pituitary adrenal axis hormones adrenocorticotropic hormone (ACTH) and glucocorticoids (GCs) both regulate BAT activity in mice. ACTH activates BAT and browning of WAT while GCs very likely counteract this effect. Long term exposure of GCs in mice also inhibit BAT activity, but this can be overruled by cold exposure, underscoring the flexibility of this tissue. Also in humans with Cushings disease we find that brown fat activity seems to be activated again after normalisation of circulating GCs. We thus show that GCs inhibit BAT activity, at least in the long turn Because women seem to have more brown fat activity than men, we show in this thesis that in both rodents and humans females have a higher potency to induce browning of WAT and have a higher prevalence of active BAT. The female hormone Estrogen is at least partly responsible for higher BAT activity in females.

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