Does obestatin modulate the hypothalamic appetite‐regulating network in peripubertal sheep?

Abstract

The participation of peripheral peptides in the processes regulating the food intake (energy homeostasis) at the central nervous system level remains unclear. This study focuses on the role of obestatin in neuronal activity within the hypothalamic appetite-regulating network in ruminants. The animals (n = 28) were randomly divided into two groups. The sheep in the control group received intracerebroventricular infusions of the Ringer-Locke solution, and the sheep in obestatin group were infused with obestatin (diluted in the Ringer-Locke solution) at 25 μg per 120 μl/hr. The series of four 1-hr infusions on 3 consecutive days were performed, and immediately after the experiment, the sheep were decapitated. Selected brain regions were fixed in situ for further immunohistochemical analysis, while the remaining ones were frozen for real-time RT-qPCR analysis. Obestatin infusion elicited changes in the neuropeptide Y (NPY) neuronal network in the hypothalamus. The results obtained show that exogenous obestatin evoked an increase in npy and agrpmRNA expression in the mediobasal hypothalamus (MBH), while the immunoreactivity for NPY was decreased in the arcuate and periventricular nuclei. The increase in cart and pomcmRNA expression in the MBH was also observed. Moreover, increased levels of gpr39 receptor and npy receptor 1 mRNA expression were evident in obestatin-infused sheep. Based on these results, it can be concluded that obestatin plays a role in the modulation of appetite-regulating network at the central level in sheep. The results obtained suggest that the underlying mechanism may involve the modification of the activity of NPY/AgRP and CART/α-MSH neurons in the arcuate nucleus.

Sex-Specific Appetite Regulation of Lipocalin-2 in High-Fat-Diet-Induced Obese Mice

“…In addition, the hypothalamus plays a crucial role in regulating feeding behavior. There are many current studies on appetite, mostly testing hormones and hypothalamic neuropeptides [37,38]. Food-related information is sent from the stomach and small intestine to the posterior brain via the afferent arm of the vagus nerve, which, like most sensory nerves, is made up of pseudounipolar neurons with cell bodies largely in the tuberous ganglia.…”

QRFP43 modulates the activity of the hypothalamic appetite regulatory centre in sheep

“…Directly after the last infusion, animals were weighed and anaesthetised intravenously with dexmedetomidine (0.05 ml/kg) and pentobarbital (80 ng/kg, Morbital ® , Vetoquinol Biowet, Poland), then euthanised by decapitation. Isolation of the selected hypothalamic structures: ARC, median eminence (ME), as well as their preservation, was conducted according to the method described in Szlis et al (2018).…”

“…The hypothalamic sections were incubated for 14 days at 4 °C with a primary NPY antiserum (rabbit anti-NPY [ref. 9528]; Sigma, Saint Louis, MO, USA), diluted at a ratio of 1:3000, following the procedure used in our laboratory (Szlis et al, 2018) with minor modifications. After incubation with primary antibodies, the sections were incubated for 2 h The colour reaction was induced by incubating sections with 0.05% 3/3-diaminobenzidine tetrahydrochloride chromogen (Sigma, Saint Louis, MO, USA) and 0.001% hydrogen peroxide in 0.05 M Tris buffer.…”

Brain-derived neurotrophic factor (BDNF) affects somatotrophic axis activity in sheep

“…Neuropeptide Y (NPY), agouti-related peptide (AgRP) and proopiomelanocortin (POMC) mRNA expression increased after BDNF intracerebroventricular (ICV) infusion (Przybył et al, 2020). On the other hand, our previous research demonstrated that several factors involved in appetite regulation processes, such as NPY, ghrelin and obestatin, can change the somatotrophic axis hormones secretory activity in sheep (Wójcik-Gładysz et al, 2014Szlis et al, 2018). It is well-known that the activity of the somatotrophic axis in the CNS may also be modulated by several factors, such as drugs, antibiotics and neurotrophins (Timmusk et al, 1993;Patapoutian and Reichardt, 2001;Kennedy, 2012).…”