2. Academic Validation
  3. Hydrogen Sulfide Attenuates High-Fat Diet-Induced Obesity: Involvement of mTOR/IKK/NF-κB Signaling Pathway

Hydrogen Sulfide Attenuates High-Fat Diet-Induced Obesity: Involvement of mTOR/IKK/NF-κB Signaling Pathway

  • Mol Neurobiol. 2022 Nov;59(11):6903-6917. doi: 10.1007/s12035-022-03004-0.
Maofang Zhao 1,  Yuan Cheng 1,  Xiaoxuan Wang 1,  Xiaoying Cui 2 3,  Xiaojing Cheng 1,  Qian Fu 1,  Yilin Song 1,  Peiquan Yu 1,  Yi Liu 4 5 6,  Yinghua Yu 7 8
Affiliations

Affiliations

  • 1 Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China.
  • 2 Queensland Centre for Mental Health Research, Wacol, QLD, Australia.
  • 3 The University of Queensland, Queensland Brain Institute, St Lucia, 4067, Australia.
  • 4 Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China. cbpeliuyinew@163.com.
  • 5 Jiangsu Key Laboratory of Brain Disease Bioinformation, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China. cbpeliuyinew@163.com.
  • 6 Department of Biophysics, School of Life Sciences, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China. cbpeliuyinew@163.com.
  • 7 Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogen Biology and Immunology, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China.
  • 8 School of Medicine, Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW, 2522, Australia.
PMID: 36053437 DOI: 10.1007/s12035-022-03004-0
Abstract

Obesity has become a public health epidemic worldwide and is associated with many diseases with high mortality including hypertension, diabetes, and heart disease. High-fat diet (HFD)-induced energy imbalance is one of the primary causes of obesity, but the underlying mechanisms are not fully elucidated. Our study showed that HFD reduced the level of hydrogen sulfide (H2S) and its catalytic Enzyme cystathionine β-synthase (CBS) in mouse hypothalamus and plasma. We found that HFD activated mTOR, IKK/NF-κB, the main pathway regulating inflammation. Activation of inflammatory pathway promoted the production of pro-inflammatory cytokines including IL-6, IL-1β, and TNF-α, which caused cell damage and loss in the hypothalamus. The disturbance of the hypothalamic neuron circuits resulted in body weight gain in HFD-induced mice. Importantly, we also showed that restoration of H2S level with NaHS or activation of CBS with SAMe attenuated HFD-induced activation of mTOR, IKK/NF-κB signaling, which reduced the inflammation and the neuronal cell loss in the hypothalamus, and also inhibited body weight gain in mice. The same effects were obtained by inhibiting mTOR or NF-κB, which suggested that mTOR and NF-κB were the critical molecular factors involved in hypothalamic inflammation. Taken together, this study identified that HFD-induced hypothalamus inflammation plays a critical role in the development of obesity. Moreover, the inhibition of hypothalamic inflammation by regaining H2S level could be a potential therapeutic to prevent the development of obesity.

Keywords

Hydrogen sulfide; Hypothalamic inflammation; NF-κB; Obesity; mTOR.

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