Light-responsive adipose-hypothalamus axis controls metabolic regulation

Tadataka Tsuji, Vladimir Tolstikov, Yang Zhang, Tian Lian Huang, Henrique Camara, Meghan Halpin, Niven R. Narain, King-Wai Yau, Matthew D. Lynes, Michael A. Kiebish and Yu-Hua Tseng ()
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Tadataka Tsuji: Harvard Medical School
Vladimir Tolstikov: BPGbio
Yang Zhang: Harvard Medical School
Tian Lian Huang: Harvard Medical School
Henrique Camara: Harvard Medical School
Meghan Halpin: Harvard Medical School
Niven R. Narain: BPGbio
King-Wai Yau: Johns Hopkins University School of Medicine
Matthew D. Lynes: Harvard Medical School
Michael A. Kiebish: BPGbio
Yu-Hua Tseng: Harvard Medical School

Nature Communications, 2024, vol. 15, issue 1, 1-19

Abstract: Abstract Light is fundamental for biological life, with most mammals possessing light-sensing photoreceptors in various organs. Opsin3 is highly expressed in adipose tissue which has extensive communication with other organs, particularly with the brain through the sympathetic nervous system (SNS). Our study reveals a new light-triggered crosstalk between adipose tissue and the hypothalamus. Direct blue-light exposure to subcutaneous white fat improves high-fat diet-induced metabolic abnormalities in an Opsin3-dependent manner. Metabolomic analysis shows that blue light increases circulating levels of histidine, which activates histaminergic neurons in the hypothalamus and stimulates brown adipose tissue (BAT) via SNS. Blocking central actions of histidine and denervating peripheral BAT blunts the effects of blue light. Human white adipocytes respond to direct blue light stimulation in a cell-autonomous manner, highlighting the translational relevance of this pathway. Together, these data demonstrate a light-responsive metabolic circuit involving adipose-hypothalamus communication, offering a potential strategy to alleviate obesity-induced metabolic abnormalities.

Date: 2024
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DOI: 10.1038/s41467-024-50866-0

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