Early Life Stress Experience May Blunt Hypothalamic Leptin Signalling

Overview

Journal J Biosci

Specialties Biochemistry
Biology

Date 2017 Feb 24

PMID 28229972

Citations 3

Authors

J H Lee

S B Yoo

J Y Kim

J Y Lee

B T Kim

K Park

J W Jahng

Affiliations

Soon will be listed here.

Abstract

The aim of this study was to investigate whether neonatal maternal separation (MS) - chronic stress experience in early life - affects the anorectic efficacy of leptin in the offspring at adolescence. Sprague-Dawley pups were separated from the dam daily for 3 h during postnatal day 1-14 or left undisturbed as non-handled controls (NH). NH and MS male pups received an intraperitoneal leptin (100 μg/kg) or saline on postnatal day (PND) 28, and then food intake and body weight gain were recorded. The hypothalamic levels of leptin-signalling-related genes, phosphorylated signal transducer and activator of transcription-3 (pSTAT3) and protein-tyrosine phosphatase 1B (PTP1B) were examined at 40 min after a single injection of leptin on PND 39 by immunohistochemistry and Western blot analysis. Leptin-induced suppressions in food intake and weight gain was observed in NH pups, but not in MS. Leptin increased pSTAT3 in the hypothalamic arcuate nucleus of NH pups, but not of MS. Interestingly, basal levels of the hypothalamic PTP1B and pSTAT3 were increased in MS pups compared with NH controls. The results suggest that neonatal MS experience may blunt the anorectic efficacy of leptin later in life, possibly in relation with increased expressions of PTP1B and/or pSTAT3 in the hypothalamus.

Citing Articles

The adipose tissue keeps the score: priming of the adrenal-adipose tissue axis by early life stress predisposes women to obesity and cardiometabolic risk.

Turner M, Dalmasso C, Loria A Front Endocrinol (Lausanne). 2024; 15:1481923.

PMID: 39493777 PMC: 11527639. DOI: 10.3389/fendo.2024.1481923.

Prenatal exposure to undernutrition is associated with a specific lipid profile predicting future brain aging.

Snowden S, Koulman A, Gaser C, la Fleur S, Roseboom T, Korosi A NPJ Aging. 2024; 10(1):42.

PMID: 39349457 PMC: 11442854. DOI: 10.1038/s41514-024-00169-x.

Early Life Stress, Brain Development, and Obesity Risk: Is Oxytocin the Missing Link?.

Colleluori G, Galli C, Severi I, Perugini J, Giordano A Cells. 2022; 11(4).

PMID: 35203274 PMC: 8870435. DOI: 10.3390/cells11040623.

References

Ribeiro A, Ceccarini G, Dupre C, Friedman J, Pfaff D, Mark A . Contrasting effects of leptin on food anticipatory and total locomotor activity. PLoS One. 2011; 6(8):e23364. PMC: 3154408. DOI: 10.1371/journal.pone.0023364. View

Wu Y, Ouyang J, Wu K, Wang S, Wen C, Xia Z . Rosiglitazone ameliorates abnormal expression and activity of protein tyrosine phosphatase 1B in the skeletal muscle of fat-fed, streptozotocin-treated diabetic rats. Br J Pharmacol. 2005; 146(2):234-43. PMC: 1576260. DOI: 10.1038/sj.bjp.0706306. View

Gao Q, Wolfgang M, Neschen S, Morino K, Horvath T, Shulman G . Disruption of neural signal transducer and activator of transcription 3 causes obesity, diabetes, infertility, and thermal dysregulation. Proc Natl Acad Sci U S A. 2004; 101(13):4661-6. PMC: 384803. DOI: 10.1073/pnas.0303992101. View

Cheng A, Uetani N, Simoncic P, Chaubey V, Lee-Loy A, McGlade C . Attenuation of leptin action and regulation of obesity by protein tyrosine phosphatase 1B. Dev Cell. 2002; 2(4):497-503. DOI: 10.1016/s1534-5807(02)00149-1. View

Jahng J, Houpt T, Kim S, Joh T, Son J . Neuropeptide Y mRNA and serotonin innervation in the arcuate nucleus of anorexia mutant mice. Brain Res. 1998; 790(1-2):67-73. DOI: 10.1016/s0006-8993(98)00049-3. View

Malendowicz L, Rucinski M, Belloni A, Ziolkowska A, Nussdorfer G . Leptin and the regulation of the hypothalamic-pituitary-adrenal axis. Int Rev Cytol. 2007; 263:63-102. DOI: 10.1016/S0074-7696(07)63002-2. View

Schwartz M, Woods S, Porte Jr D, Seeley R, Baskin D . Central nervous system control of food intake. Nature. 2000; 404(6778):661-71. DOI: 10.1038/35007534. View

Yoo S, Ryu V, Park E, Kim B, Kang D, Lee J . The arcuate NPY, POMC, and CART expressions responding to food deprivation are exaggerated in young female rats that experienced neonatal maternal separation. Neuropeptides. 2011; 45(5):343-9. DOI: 10.1016/j.npep.2011.07.005. View

Wronska A, Sledzinski T, Goyke E, Lawniczak A, Wierzbicki P, Kmiec Z . Short-term calorie restriction and refeeding differently affect lipogenic enzymes in major white adipose tissue depots of young and old rats. J Physiol Pharmacol. 2014; 65(1):117-26. View

10.

Lukkes J, Watt M, Lowry C, Forster G . Consequences of post-weaning social isolation on anxiety behavior and related neural circuits in rodents. Front Behav Neurosci. 2009; 3:18. PMC: 2737489. DOI: 10.3389/neuro.08.018.2009. View

11.

Heiman M, Ahima R, Craft L, Schoner B, STEPHENS T, Flier J . Leptin inhibition of the hypothalamic-pituitary-adrenal axis in response to stress. Endocrinology. 1997; 138(9):3859-63. DOI: 10.1210/endo.138.9.5366. View

12.

Considine R, Sinha M, Heiman M, Kriauciunas A, STEPHENS T, Nyce M . Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med. 1996; 334(5):292-5. DOI: 10.1056/NEJM199602013340503. View

13.

Chiarreotto-Ropelle E, Pauli L, Katashima C, Pimentel G, Picardi P, Silva V . Acute exercise suppresses hypothalamic PTP1B protein level and improves insulin and leptin signaling in obese rats. Am J Physiol Endocrinol Metab. 2013; 305(5):E649-59. DOI: 10.1152/ajpendo.00272.2013. View

14.

Asante-Appiah E, Kennedy B . Protein tyrosine phosphatases: the quest for negative regulators of insulin action. Am J Physiol Endocrinol Metab. 2003; 284(4):E663-70. DOI: 10.1152/ajpendo.00462.2002. View

15.

Qin Z, Zhou X, Pandey N, Vecchiarelli H, Stewart C, Zhang X . Chronic stress induces anxiety via an amygdalar intracellular cascade that impairs endocannabinoid signaling. Neuron. 2015; 85(6):1319-31. DOI: 10.1016/j.neuron.2015.02.015. View

16.

Jahng J, Kim N, Ryu V, Yoo S, Kim B, Kang D . Dexamethasone reduces food intake, weight gain and the hypothalamic 5-HT concentration and increases plasma leptin in rats. Eur J Pharmacol. 2008; 581(1-2):64-70. DOI: 10.1016/j.ejphar.2007.11.029. View

17.

Zabolotny J, Stricker-Krongrad A, Haj F, Wang Y, Minokoshi Y, Kim Y . PTP1B regulates leptin signal transduction in vivo. Dev Cell. 2002; 2(4):489-95. DOI: 10.1016/s1534-5807(02)00148-x. View

18.

Konishi N, Otaka M, Odashima M, Jin M, Wada I, Komatsu K . Systemic stress increases serum leptin level. J Gastroenterol Hepatol. 2006; 21(7):1099-102. DOI: 10.1111/j.1440-1746.2006.04132.x. View

19.

Ahima R, Prabakaran D, Mantzoros C, Qu D, Lowell B, Maratos-Flier E . Role of leptin in the neuroendocrine response to fasting. Nature. 1996; 382(6588):250-2. DOI: 10.1038/382250a0. View

20.

Xiong H, Du W, Wang J, Wang Y, Tang J, Hong J . Constitutive activation of STAT3 is predictive of poor prognosis in human gastric cancer. J Mol Med (Berl). 2012; 90(9):1037-46. DOI: 10.1007/s00109-012-0869-0. View