Leptin Sensitivity in the Developing Rat Hypothalamus

Sep 18, 2007Endocrinology

Leptin response in the developing brain region that controls hunger in rats

AI simplified

GLP-1 Therapies on OpenScience ↗PubMed ↗DOI ↗

Abstract

Leptin regulates food intake and body weight through the hypothalamic arcuate nucleus (ARC) but shows limited effectiveness in early postnatal development.

In embryonic rat neuronal cultures, leptin did not activate key signaling pathways related to its function.
Leptin decreased levels of specific hormones, including proopiomelanocortin and neuropeptide Y, while lowering somatostatin secretion.
In vivo leptin challenges revealed that certain hormone levels remained largely unchanged during early postnatal stages (P7, P14, P21) compared to adult rats.
Leptin stimulation increased suppressor of cytokine signaling-3 mRNA levels in several hypothalamic regions at P14, P21, and P28, but not at P7.
The findings indicate that the developmental stages impact leptin receptor signaling and sensitivity in the hypothalamus.

AI simplified

In adults, the adipocyte-derived hormone, leptin, regulates food intake and body weight principally via the hypothalamic arcuate nucleus (ARC). During early postnatal development, leptin functions to promote the outgrowth of neuronal projections from the ARC, whereas a selective insensitivity to the effects of leptin on food intake appears to exist. To investigate the mechanisms underlying the inability of leptin to regulate food intake during early development, leptin signaling was analyzed both in vitro using primary cultures of rat embryonic ARC neurones and in vivo by challenging early postnatal rats with leptin. In neuronal cultures, despite the presence of key components of the leptin signaling pathway, no detectable activation of either signal transducer and activator of transcription 3 or the MAPK pathways by leptin was detected. However, leptin down-regulated mRNA levels of proopiomelanocortin and neuropeptide Y and decreased somatostatin secretion. Leptin challenge in vivo at postnatal d (P) 7, P14, P21, and P28 revealed that, in contrast to adult and P28 rats, mRNA levels of neuropeptide Y, proopiomelanocortin, agouti-related peptide and cocaine- and amphetamine-regulated transcript were largely unaffected at P7, P14, and P21. Furthermore, leptin stimulation increased the suppressor of cytokine signaling-3 mRNA levels at P14, P21, and P28 in several hypothalamic nuclei but not at P7, indicating that selective leptin insensitivity in the hypothalamus is coupled to developmental shifts in leptin receptor signaling. Thus, the present study defines the onset of leptin sensitivity in the regulation of energy homeostasis in the developing hypothalamus.

Full Text

Full text is available at the source.

View full text (PDF) ↗View full text ↗

Leptin Sensitivity in the Developing Rat Hypothalamus

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the glp-1 therapies brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the glp-1 therapies brief