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A central-acting connexin inhibitor, INI-0602, prevents high-fat diet-induced feeding pattern disturbances and obesity in mice

Overview of attention for article published in Molecular Brain, May 2018
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Title
A central-acting connexin inhibitor, INI-0602, prevents high-fat diet-induced feeding pattern disturbances and obesity in mice
Published in
Molecular Brain, May 2018
DOI 10.1186/s13041-018-0372-9
Pubmed ID
Authors

Tsutomu Sasaki, Rika Numano, Hiromi Yokota-Hashimoto, Sho Matsui, Naobumi Kimura, Hideyuki Takeuchi, Tadahiro Kitamura

Abstract

A high-fat diet (HFD) causes obesity by promoting excessive energy intake, and simultaneously, by disturbing the timing of energy intake. Restoring the feeding pattern is sufficient to prevent HFD-induced obesity in mice. However, the molecular mechanism(s) underlying HFD-induced feeding pattern disturbances remain elusive. Saturated fatty acids activate microglia and cause hypothalamic inflammation. Activated microglia cause neuroinflammation, which spreads via inflammatory cytokines and gap-junction hemichannels. However, the role of gap-junction hemichannels in HFD-induced obesity remains unaddressed. We used a novel, central-acting connexin inhibitor, INI-0602, which has high affinity for gap junction hemichannels and does not affect the induction of inflammatory cytokines. We analyzed ad libitum feeding behavior and locomotor activity in mice that were fed normal chow (NC), a HFD with elevated saturated fatty acids (SFAs), or a HFD with very high SFAs. We found that HFD feeding induced acute hyperphagia, mainly during the light cycle. Feeding pattern disturbances were more pronounced in mice that consumed the HFD with very high SFAs than in mice that consumed the HFD with elevated SFAs. When INI-0602 was administered before the HFD was introduced, it blocked the feeding pattern disturbance, but not locomotor activity disturbances; moreover, it prevented subsequent diet-induced obesity. However, when INI-0602 was administered after the HFD had disturbed the feeding pattern, it failed to restore the normal feeding pattern. Therefore, we propose that SFAs in HFDs played a major role in disrupting feeding patterns in mice. Moreover, the feeding pattern disturbance required the function of central, gap junction hemichannels at the initiation of a HFD. However, altering hemichannel function after the feeding pattern disturbance was established had no effect. Thus, preventing the occurrence of a feeding pattern disturbance by blocking the hemichannel pathway was associated with the prevention of the HFD-induced obesity in mice.

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The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 18 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 18 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 5 28%
Student > Master 3 17%
Student > Ph. D. Student 2 11%
Student > Postgraduate 2 11%
Researcher 2 11%
Other 1 6%
Unknown 3 17%
Readers by discipline Count As %
Nursing and Health Professions 4 22%
Agricultural and Biological Sciences 3 17%
Neuroscience 2 11%
Biochemistry, Genetics and Molecular Biology 1 6%
Immunology and Microbiology 1 6%
Other 3 17%
Unknown 4 22%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 25 June 2018.
All research outputs
#10,468,082
of 13,133,585 outputs
Outputs from Molecular Brain
#460
of 603 outputs
Outputs of similar age
#200,999
of 268,779 outputs
Outputs of similar age from Molecular Brain
#3
of 4 outputs
Altmetric has tracked 13,133,585 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 603 research outputs from this source. They receive a mean Attention Score of 4.3. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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