Human adipose tissue is a putative direct target of daytime orexin with favorable metabolic effects: A cross-sectional study

Nir Goldstein, Hiroshi Tsuneki, Nikhil Bhandarkar, Eleonora Aimaretti, Yulia Haim*, Kanta Kon, Kiyofumi Sato, Tsutomu Wada, Idit F. Liberty, Boris Kirshtein, Oleg Dukhno, Nitzan Maixner, Yftach Gepner, Toshiyasu Sasaoka, Assaf Rudich*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: Orexin/hypocretin (Ox) and its receptors (OxR), a neuroendocrine system centrally regulating sleep/wakefulness, were implicated in the regulation of peripheral metabolism. It was hypothesized that human adipose tissue constitutes a direct target of the OxA/OxR system that associates with distinct metabolic profile(s). Methods: Serum Ox levels and abdominal subcutaneous and visceral adipose tissue expression of Ox/HCRT, OxR1/HCRTR1, and OxR2/HCRTR2 were measured in n = 81 patients. Results: Higher morning circulating Ox levels were associated with improved lipid profile and insulin sensitivity, independently of BMI (β = −0.363, p = 0.018 for BMI-adjusted homeostatic model of insulin resistance). Adipose HCRT mRNA was detectable in <20% of patients. Visceral HCRT expressers were mostly (80%) males and, compared with nonexpressers, had lower total and LDL cholesterol. HCRTR1 was readily detectable, and HCRTR2 was undetectable. HCRTR1 mRNA and OxR1 protein expression were higher in subcutaneous than visceral adipose tissue, and among nonobese patients, patients with obesity, and patients with obesity and T2DM were 3.4 (1.0), 0.7 (0.1), 0.6 (0.1) (AU) (p < 0.001) and 1.0 (0.2), 0.5 (0.1), 0.4 (0.1) (AU) (p = NS), respectively. Higher visceral HCRTR1 expression was associated with lower fasting insulin and homeostatic model of insulin resistance, also after adjusting for BMI. In human adipocytes, HCRTR1 expression did not exhibit significant oscillation. Conclusions: Human adipose tissue is a putative direct target of the OxA-OxR1 system, with higher morning input being associated with improved metabolic profile.

Original languageEnglish
Pages (from-to)1857-1867
Number of pages11
JournalObesity
Volume29
Issue number11
DOIs
StatePublished - Nov 2021

Funding

FundersFunder number
National Institute of Ecology
Japan Society for the Promotion of Science
Israel Science Foundation124/17, 2176/19
Università degli Studi di Torino

    Fingerprint

    Dive into the research topics of 'Human adipose tissue is a putative direct target of daytime orexin with favorable metabolic effects: A cross-sectional study'. Together they form a unique fingerprint.

    Cite this