Postnatal early overfeeding induces hypothalamic higher SOCS3 expression and lower STAT3 activity in adult rats

Rodrigues, Ana Lúcia; Moura, Egberto Gaspar de; Passos, M. C. F.; Trevenzoli, Isis Hara; Conceição, Ellen Paula Santos da; Bonono, Isabela Teixeira; Neto, José Firmino Nogueira; Lisboa, Patrícia Cristina

doi:10.1016/j.jnutbio.2009.11.013

Cited by 68 publications

(74 citation statements)

References 77 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The aim of this study was to evaluate the adaptability of HPT and HPA axes to a 48-h period of fasting in adult animals that presented hyperleptinemia and overweight during lactation due to litter size reduction. Early-overfed adult rats allowed to feed ad libitum exhibited similar changes to those previously observed by others regarding body weight, leptin levels, and mRNA expression of ObRb and NPY in the arcuate nucleus (Lopez et al 2005, Rodrigues et al 2011. In addition, the expected hyperleptinemia and overweight were present in weaned early-overfed animals.…”

Section: Discussionsupporting

confidence: 83%

“…As we discuss below, we found a deregulated adrenal axis in early-overfed adult rats that could contribute to the unchanged circulating leptin levels in this group. Rodrigues et al (2011) have also reported leptin levels similar to controls in early-overfed groups using the same model. We found enhanced ObRb and SOCS3 expression in the ARC of early-overfed animals, supporting the resistance of this nucleus to the effects of leptin, as has been suggested by other authors (Rodrigues et al 2011).…”

Section: Discussionsupporting

confidence: 54%

“…Rodrigues et al (2011) have also reported leptin levels similar to controls in early-overfed groups using the same model. We found enhanced ObRb and SOCS3 expression in the ARC of early-overfed animals, supporting the resistance of this nucleus to the effects of leptin, as has been suggested by other authors (Rodrigues et al 2011). SOCS3 is a negative regulator of the leptin signaling cascade; hence its higher expression may impair the positive and negative effects of leptin on the synthesis of anorexigenic and orexigenic peptides respectively.…”

Section: Discussionsupporting

confidence: 54%

See 2 more Smart Citations

Pro-TRH and pro-CRF expression in paraventricular nucleus of small litter-reared fasted adult rats

Aréchiga-Ceballos

Alvarez-Salas

Matamoros-Trejo

et al. 2014

Journal of Endocrinology

View full text Add to dashboard Cite

Neuroendocrine axes adapt to nutrient availability. During fasting, the function of the hypothalamus–pituitary–thyroid axis (HPT) is reduced, whereas that of the hypothalamus–pituitary–adrenal axis (HPA) is increased. Overfeeding-induced hyperleptinemia during lactation may alter the regulatory set point of neuroendocrine axes and their adaptability to fasting in adulthood. Hyperleptinemia is developed in rodents by litter size reduction during lactation; adult rats from small litters become overweight, but their paraventricular nucleus (PVN) TRH synthesis is unchanged. It is unclear whether peptide expression still responds to nutrient availability. PVN corticotropin-releasing factor (CRF) expression has not been evaluated in this model. We analyzed adaptability of HPT and HPA axes to fasting-induced low leptin levels of reduced-litter adult rats. Offspring litters were reduced to 2–3/dam (early-overfed) or maintained at 8/dam (controls, C). At 10 weeks old, a subset of animals from each group was fasted for 48 h and leptin, corticosterone, and thyroid hormones serum levels were analyzed. In brain, expressions of leptin receptor, NPY and SOCS3, were evaluated in arcuate nucleus, and those of proTRH and proCRF in PVN by real-time PCR. ProTRH expression in anterior and medial PVN subcompartments was assayed byin situhybridization. Early-overfed adults developed hyperphagia and excessive weight, together with decreased proTRH expression in anterior PVN, supporting the anorexigenic effects of TRH. Early-overfed rats presented low PVN proTRH synthesis, whereas fasting did not induce a further reduction. Fasting-induced stress was unable to increase corticosterone levels, contributing to reduced body weight loss in early-overfed rats. We concluded that early overfeeding impaired the adaptability of HPT and HPA axes to excess weight and fasting in adults.

show abstract

Section: Discussionsupporting

confidence: 83%

Section: Discussionsupporting

confidence: 54%

Section: Discussionsupporting

confidence: 54%

See 1 more Smart Citation

Pro-TRH and pro-CRF expression in paraventricular nucleus of small litter-reared fasted adult rats

Aréchiga-Ceballos

Alvarez-Salas

Matamoros-Trejo

et al. 2014

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…A previous study has also reported that mice resistant to leptin during pregnancy have defective leptin JAK2-STAT3 signaling in the PVN [45]. SOCS3 is a leptin-inducible inhibitor of leptin JAK2-STAT3 signaling, and it has been suggested to mediate central leptin resistance in obesity [46]. We have shown that SOCS3 was significantly increased in the PVN following icv injection of PA, which may contribute to impaired leptin STAT3 signaling in the hypothalamus and the development of central leptin resistance.…”

Section: Discussionsupporting

confidence: 50%

Palmitic acid induces central leptin resistance and impairs hepatic glucose and lipid metabolism in male mice

Cheng

Szabo

et al. 2015

The Journal of Nutritional Biochemistry

View full text Add to dashboard Cite

X. (2015). Palmitic acid induces central leptin resistance and impairs hepatic glucose and lipid metabolism in male mice. Journal of Nutritional Biochemistry, 26 (5), 541-548. Palmitic acid induces central leptin resistance and impairs hepatic glucose and lipid metabolism in male mice AbstractThe consumption of diets rich in saturated fat largely contributes to the development of obesity in modern societies. A diet high in saturated fats can induce inflammation and impair leptin signaling in the hypothalamus. However, the role of saturated fatty acids on hypothalamic leptin signaling, and hepatic glucose and lipid metabolism remains largely undiscovered. In this study, we investigated the effects of intracerebroventricular (icv) administration of a saturated fatty acid, palmitic acid (PA, C16:0), on central leptin sensitivity, hypothalamic leptin signaling, inflammatory molecules and hepatic energy metabolism in C57BL/6 J male mice. We found that the icv administration of PA led to central leptin resistance, evidenced by the inhibition of central leptin's suppression of food intake. Central leptin resistance was concomitant with impaired hypothalamic leptin signaling ( JAK2-STAT3, PKB/Akt-FOXO1) and a pro-inflammatory response (TNF-α, IL1-β, IL-6 and pIκBa) in the mediobasal hypothalamus and paraventricular hypothalamic nuclei. Furthermore, the pre-administration of icv PA blunted the effect of leptin-induced decreases in mRNA expression related to gluconeogenesis (G6Pase and PEPCK), glucose transportation (GLUT2) and lipogenesis (FAS and SCD1) in the liver of mice. Therefore, elevated central PA concentrations can induce pro-inflammatory responses and leptin resistance, which are associated with disorders of energy homeostasis in the liver as a result of diet-induced obesity. Abstract:The consumption of diets rich in saturated fat largely contributes to the development of obesity in modern societies. A diet high in saturated fats can induce inflammation and impair leptin signaling in the hypothalamus. However, the role of saturated fatty acids on hypothalamic leptin signaling, and hepatic glucose and lipid metabolism remains largely undiscovered. In this study, we investigated the effects of intracerebroventricular (icv) administration of a saturated fatty acid, palmitic acid (PA, C16:0), on central leptin sensitivity, hypothalamic leptin signaling, inflammatory molecules, and hepatic energy metabolism in C57BL/6J male mice. We found that the icv administration of PA led to central leptin resistance, evidenced by the inhibition of central leptin's suppression of food intake. Central leptin resistance was concomitant with impaired hypothalamic leptin signaling (JAK2-STAT3, PKB/Akt-FOXO1), and a pro-inflammatory response (TNF-α, IL1-β, IL-6, and pIκBa) in the mediobasal hypothalamus and paraventricular hypothalamic nuclei.Furthermore, the pre-administration of icv PA blunted the effect of leptin-induced decreases in mRNA expression related to gluconeogenesis (G6Pase and PEPCK), glucose transportation (GLUT2), ...

show abstract

“…Leptin directly stimulates TRH in the hypothalamic PVN nucleus as well as the production and secretion of TSH in the pituitary (Itoh et al 2003). In PN180, although SL rats present normal TSH and leptin levels (Rodrigues et al 2009, they exhibited leptin resistance at the level of the hypothalamus and pituitary level (Rodrigues et al 2009, Rodrigues et al 2011). This finding is in agreement with the decrease observed in TRH protein expression in the hypothalamus and the decreased intra-pituitary TSH with lower basal and TRH-stimulated TSH secretion.…”

Section: Discussionmentioning

confidence: 99%

Postnatal overnutrition programs the thyroid hormone metabolism and function in adulthood

Lisboa

Conceição

Oliveira

et al. 2015

Journal of Endocrinology

View full text Add to dashboard Cite

Early overnutrition (EO) during lactation leads to obesity, leptin resistance and lower thyroid hormone (TH) levels during adulthood. To better understand the biological significance of this thyroid hypofunction, we studied the long-term effects of postnatal EO on both the function of hypothalamic-pituitary-thyroid (HPT) axis and the metabolism and action of TH. To induce EO, the litter size was reduced to three pups per litter (small litter (SL) group) on the third day of lactation. In the controls (normal litter group), litter size was adjusted to 10 pups per litter. Rats were killed at PN180. TRH content and in vitro TSH were evaluated. Iodothyronine deiodinase (D1 and D2) activities were measured in different tissues. Mitochondrial a-glycerol-3-phosphate dehydrogenase (mGPD), uncoupling protein 1 (UCP1) and TH receptor (TRb1) were evaluated to assess TH action. The SL group presented lower TRH, intra-pituitary and released TSH levels, despite unchanged plasma TSH. They presented lower D1 activity in thyroid, muscle and white adipose tissue (WAT) and higher D2 activity in the hypothalamus, pituitary, brown adipose tissue (BAT) and WAT, which confirmed the hypothyroidism. UCP1 in BAT and TRb1 in WAT were decreased, which can contribute to a lower catabolic status. Despite the lower TH, the D2 activity in the thyroid, heart and testes was unchanged. Hepatic D1, mGPD and TRb1 were also unchanged in SL rats, suggesting that the TH conversion and action were preserved in the liver, even with lower TH. Thus, this model indicates that postnatal EO changes thyroid function in adult life in a tissue-specific way, which can help in the understanding of obesogenesis.

show abstract

Postnatal early overfeeding induces hypothalamic higher SOCS3 expression and lower STAT3 activity in adult rats

Cited by 68 publications

References 77 publications

Pro-TRH and pro-CRF expression in paraventricular nucleus of small litter-reared fasted adult rats

Pro-TRH and pro-CRF expression in paraventricular nucleus of small litter-reared fasted adult rats

Palmitic acid induces central leptin resistance and impairs hepatic glucose and lipid metabolism in male mice

Postnatal overnutrition programs the thyroid hormone metabolism and function in adulthood

Contact Info

Product

Resources

About