Hypothyroidism induces hypophagia associated with alterations in protein expression of neuropeptide Y and proopiomelanocortin in the arcuate nucleus, independently of hypothalamic nuclei-specific changes in leptin signaling.

Hypothyroidism induces hypophagia associated with alterations in protein expression of neuropeptide Y and proopiomelanocortin in the arcuate nucleus, independently of hypothalamic nuclei-specific changes in leptin signaling.

Thyroid. 2015 Nov 5;

Authors: Calvino C, Império GE, Wilieman M, Costa-E-Sousa RH, Souza LL, Travenzoli I, Pazos-Moura CC

Abstract
BACKGROUND: Thyroid hormone and leptin are essential regulators of energy homeostasis. Both hormones stimulate energy expenditure but have opposite effects on appetite. The mechanisms behind food intake regulation in thyroid dysfunctions are poorly understood. We have shown that hypothyroid rats exhibited impaired leptin anorexigenic effect and signaling in total hypothalamus, even though they were hypophagic. We hypothesized that hypothyroidism modulates the expression of neuropeptides: orexigenic neuropeptide Y (NPY) and anorexigenic proopiomelanocortin (POMC), independently of inducing nuclei-specific changes in hypothalamic leptin signaling.
METHODS: Adult male rats were rendered hypothyroid by administration of 0.03% methimazole in the drinking water, for 21 days. Protein content of NPY, POMC and of leptin signaling (the signal transducer and activator of transcription 3 (STAT3) pathway) were evaluated by western blot, and mRNA levels by real time RT-PCR in arcuate (ARC), ventromedial (VMN) and paraventricular (PVN) hypothalamic nuclei isolated from euthyroid (eu) and hypothyroid (hypo) rats. Leptin anorexigenic effect was tested by recording food intake for 2 hours after intracerebroventricular (i.c.v.) administration of leptin. Statistical differences were considered at p≤0.05.
RESULTS: Hypothyroidism was confirmed by decreased serum triiodothyronine, thyroxine, and increased TSH, in addition to increased levels of pro-TRH mRNA in PVN and Dio2 mRNA in ARC of hypo rats. Hypothyroidism decreased body weight and food intake associated with decreased protein content of NPY and increased content of POMC in the ARC. Conversely, hypothyroidism induced central resistance to the acute anorexigenic effect of leptin, since while euthyroid rats displayed reduced food intake after leptin i.c.v. injection, hypothyroid rats showed no response. Hypothyroid rats exhibited decreased leptin receptor (ObRb) protein content in ARC and VMN, but not in PVN nucleus. ObRb protein changes were concomitant with decreased phosphorylated STAT3 in the ARC, and decreased total STAT3 in VMN and PVN. However, hypothyroidism did not affect mRNA levels of Lepr or Stat3 in the hypothalamic nuclei.
CONCLUSIONS: Experimental hypothyroidism induced negative energetic balance accompanied by decreased NPY and increased POMC protein content in the ARC resulting in predominance of anorexigenic pathways, despite of central leptin resistance and impairment of leptin signaling cascade in a nuclei-specific manner.

PMID: 26538454 [PubMed - as supplied by publisher]

from #ENT-PubMed via ola Kala on Inoreader http://ift.tt/20zp4wY
via IFTTT