Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Jun;1863(6):549-562.
doi: 10.1016/j.bbalip.2018.02.009. Epub 2018 Mar 6.

Nobiletin protects against insulin resistance and disorders of lipid metabolism by reprogramming of circadian clock in hepatocytes

Guoyuan Qi  1 , Rui Guo  1 , Haoyu Tian  1 , Lixia Li  1 , Hua Liu  1 , Yashi Mi  1 , Xuebo Liu  2
Affiliations

Nobiletin protects against insulin resistance and disorders of lipid metabolism by reprogramming of circadian clock in hepatocytes

Guoyuan Qi et al. Biochim Biophys Acta Mol Cell Biol Lipids. 2018 Jun.

Abstract

Scope: Circadian clock plays a principal role in orchestrating our daily physiology and metabolism, and their perturbation can evoke metabolic diseases such as fatty liver and insulin resistance. Nobiletin (NOB) has been demonstrated to possess antitumor and neuroprotective activities. The objective of the current study is to determine potential effects of NOB on modulating the core clock gene Bmal1 regarding ameliorating glucolipid metabolic disorders.

Results: Our results revealed that NOB partially reverse the relatively shallow daily oscillations of circadian clock genes and reset phase-shifting circadian rhythms in primary hepatocytes under metabolic disorders conditions. Importantly, NOB was found to be effective at amplifying glucose uptake via stimulating IRS-1/AKT signaling pathway, as well as blunting palmitate-induced lipogenesis in HepG2 cells via modulating AMPK-Sirt1 signaling pathway and key enzymes of de novo lipogenesis in a Bmal1-dependent manner. NOB attenuated palmitate-stimulated excessive secretions of ROS, restored the depletions of mitochondrial membrane potential, which is similar to the recovery in expressions of mitochondrial respiration complex I-IV.

Conclusion: This study is the first to provide compelling evidences that NOB prevent cellular glucolipid metabolic imbalance and mitochondrial function in a Bmal1-dependent manner. Overall, NOB may serve as a nutritional preventive strategy in recovering metabolic disorders relevant to circadian clock.

Keywords: AMPK; Bmal1; Circadian clock; Glucose and lipid metabolism; Insulin resistance; Nobiletin.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types

MeSH terms

LinkOut - more resources

  NODES
twitter 2