Cited by 65Regulation of Appetite and ObesityAdipose Tissue and MetabolismLipid metabolism and biosynthesis

Leucine deprivation stimulates fat loss via increasing CRH expression in the hypothalamus and activating the sympathetic nervous system

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Cheng, Ying, Zhang, Qian, Meng, Qingshu, Xia, Tingting, Huang, Zhiying, Wang, Chunxia, Liu, Bin, Chen, Shanghai +3 more·2011·Molecular Endocrinology

Abstract

We previously showed that leucine deprivation decreases abdominal fat mass largely by increasing energy expenditure, as demonstrated by increased lipolysis in white adipose tissue (WAT) and uncoupling protein 1 (UCP1) expression in brown adipose tissue (BAT). The goal of the present study was to investigate the possible involvement of central nervous system (CNS) in this regulation and elucidate underlying molecular mechanisms. For this purpose, levels of genes and proteins related to lipolysis in WAT and UCP1 expression in BAT were analyzed in wild-type mice after intracerebroventricular administration of leucine or corticotrophin-releasing hormone antibodies, or in mice deleted for three β-adrenergic receptors, after being maintained on a leucine-deficient diet for 7 d. Here, we show that intracerebroventricular administration of leucine significantly attenuates abdominal fat loss and blocks activation of hormone sensitive lipase in WAT and induction of UCP1 in BAT in leucine-deprived mice. Furthermore, we provide evidence that leucine deprivation stimulates fat loss by increasing expression of corticotrophin-releasing hormone in the hypothalamus via activation of stimulatory G protein/cAMP/protein kinase A/cAMP response element-binding protein pathway. Finally, we show that the effect of leucine deprivation on fat loss is mediated by activation of the sympathetic nervous system. These results suggest that CNS plays an important role in regulating fat loss under leucine deprivation and thereby provide novel and important insights concerning the importance of CNS leucine in the regulation of energy homeostasis.

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Authors
Cheng, Y., Zhang, Q., Meng, Q., Xia, T., Huang, Z., Wang, C., Liu, B., Chen, S., Xiao, F., Du, Y., & Guo, F.
Affiliations
Chinese Academy of Sciences (CN)
Venue
Molecular Endocrinology
Published
2011-09-01
Volume
25
Issue
9
Pages
1624-1635
ISSN
  • 0888-8809 (ISSN-L)
  • 1944-9917
OpenAlex
W1970368623
Cited by
65
References
51
Citations by year
2026: 3 · 2025: 5 · 2023: 3 · 2022: 2 · 2021: 4 · 2020: 4 · 2019: 4 · 2018: 5 · 2017: 6 · 2016: 4 · 2015: 2 · 2014: 7 · 2013: 6 · 2012: 10
FWCI
3.39
Type
journal article
Language
en
Open access
Locations
  • Molecular Endocrinology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Chinese Academy of Sciences (2009CB919001, SIBS2008006)
  • Directorate for Biological Sciences
  • National Key Research and Development Program of China
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
Keywords
leucine deprivation, fat loss, corticotropin-releasing factor, hypothalamus, sympathetic nervous system, white adipose tissue lipolysis, brown adipose tissue, UCP1, hormone-sensitive lipase, cAMP signaling, protein kinase A, energy homeostasis
MeSH terms
Cyclic AMP, Animals, Antibodies, Adipose Tissue, Brown, Corticotropin-Releasing Hormone, Energy Metabolism, Hypothalamus, Injections, Intraventricular, Leucine, Mice, Inbred C57BL, Receptors, Adrenergic, beta, Sympathetic Nervous System, Signal Transduction, Rats, Sprague-Dawley, Cyclic AMP Response Element-Binding Protein, Cyclic AMP-Dependent Protein Kinases, Mice, Knockout, GTP-Binding Protein alpha Subunits, Gs, Abdominal Fat, Adiposity, Mice, Rats

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