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Biochim Biophys Acta Mol Basis Dis. 2018 Oct;1864(10):3281-3291. doi: 10.1016/j.bbadis.2018.07.014. Epub 2018 Jul 20.

Cystathionine beta synthase-hydrogen sulfide system in paraventricular nucleus reduced high fatty diet induced obesity and insulin resistance by brain-adipose axis.

Author information

1
Department of Physiology and Pathophysiology, Department of Biomedical Informatics, MOE Key Lab of Cardiovascular Sciences, Center for Noncoding RNA Medicine, School of Basic Medical Science, Peking University, PR China.
2
Department of Cardiology, Johns Hopkins School of Medicine, USA.
3
Hypertension Center, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, State Key Laboratory of Cardiovascular Disease, Beijing, PR China.
4
Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, PR China.
5
Department of Physiology and Pathophysiology, Department of Biomedical Informatics, MOE Key Lab of Cardiovascular Sciences, Center for Noncoding RNA Medicine, School of Basic Medical Science, Peking University, PR China; Hypertension Center, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, State Key Laboratory of Cardiovascular Disease, Beijing, PR China. Electronic address: bingeng@hsc.pku.edu.cn.

Abstract

Hydrogen sulfide (H2S) is an essential neuromodulator, generates by cystathionine β synthase (CBS) or 3-mecaptopyruvate sulfurtransferase (3MST) in the brain. H2S can mediate paraventricular nucleus (PVN) neuron activity, and regulate neuroendocrine hormones secretion. On the other hand, CBS deficiency caused metabolic disorder and body weight reduction. However, whether CBS/H2S of PVN regulates neuroendocrine hormones to mediate energy metabolism is unknown. Here, we first identified the CBS co-localization with thyrotropin-releasing hormone (TRH) and corticotropin releasing hormone (CRH) positive neurons. In HFD induced obese rats, CBS protein of hypothalamus decreased. By contrast, overexpression CBS in PVN via lentivirus, lowered food uptake, body weight and fat mass, and reduced blood glucose, lipid disorders and insulin resistance. Intriguingly, CBS overexpression increased the pre-TRH expression, slightly elevated plasma thyroxine and thyrotropin level, but decreased the plasma ACTH and corticosterone level. Then, we found that mTOR activation contributed to pre-TRH up-regulation by CBS/H2S system. In db/db obese mice, hypothalamus CBS/H2S system also down-regulated association with reduction pre-TRH expression; in contrast, CBS overexpression in PVN slightly elevated plasma leptin. Next, leptin stimulated FOXO3a nuclear translocation, increased FOXO3a binding activity to two binding sites of CBS promoter, and then enhanced CBS protein expression. In conclusion, leptin activates neuron CBS-H2S system by FOXO3a, regulates neuroendocrine hormones to modulate the energy homeostasis, thus highlights a new brain-adipose feedback axis in energy metabolism.

KEYWORDS:

Cystathionine β synthase; FOXO3a; Hydrogen sulfide; Leptin; Obesity; Paraventricular nucleus

PMID:
30010047
DOI:
10.1016/j.bbadis.2018.07.014
[Indexed for MEDLINE]

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