The arcuate nucleus of the hypothalamus (ARH) is involved in the control of
energy homeostasis. Leptin - an adipocyte derived hormone - is known to
act on the hypothalamic nuclei and thus to control body weight by food intake
reduction. Oxidative stress is believed to be implicated in leptin signalling. However,
its relevance for leptin-induced signal transduction within ARH remains
unclear. The goal of the study was to investigate the effect of fasting on morphological
alterations of the neuronal endoplasmic reticulum/Golgi network as
well as on the expression of leptin receptors in the arcuate nucleus of aged
rats. Male Wistar rats, aged 24 months, were fasted for 96 hours. The control
animals were fed ad libitum. Membranous whorls in the ARH neurons were
visualized using the electron microscopy technique. Leptin receptors in the
membranes of ARH neurons were determined immunohistochemically (IHC),
and soluble leptin receptors in the plasma as well as plasma isoprostanes were
quantified immunochemically (ELISA). An intense formation of membranous
whorls was observed, directly associated with the cisternae of the rough endoplasmic
reticulum, as well as lamellar bodies. Interestingly, the whorls were
often localized near a well-developed Golgi complex. Moreover, some Golgi
complexes displayed an early stage of whorl formation. Groups of residual
lipofuscin granules were found in the immediate proximity of the whorls. An
increased immunoreactivity with neuronal leptin receptors suggests that hypersensitive
neurons may still effectively respond to the fasting serum levels of
leptin, mediating ultrastructural transformation of ARH neurons during short-term fasting. Having observed a significant accumulation of lipofuscin granules
and a marked increase of total 8-isoprostane serum level in the fasting rats, we
hypothesize that signal transduction within the neurons of ARH is dependent
on oxidative stress phenomena
