Light-responsive adipose-hypothalamus axis controls metabolic regulation

Authors

Tadataka Tsuji, Section on Integrative Physiology and Metabolism, Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA.
Vladimir Tolstikov, BPGbio, Framingham, MA, USA.
Yang Zhang, Section on Integrative Physiology and Metabolism, Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA.
Tian Lian Huang, Section on Integrative Physiology and Metabolism, Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA.
Henrique Camara, Section on Integrative Physiology and Metabolism, Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA.
Meghan Halpin, Section on Integrative Physiology and Metabolism, Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA.
Niven R. Narain, BPGbio, Framingham, MA, USA.
King-Wai Yau, Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Matthew D. Lynes, MaineHealthFollow

Document Type

Article

Publication Date

8-8-2024

Institution/Department

Center for Molecular Medicine

Journal Title

Nature communications

MeSH Headings

Animals; Hypothalamus (metabolism, radiation effects); Light; Humans; Adipose Tissue, Brown (metabolism); Male; Mice; Obesity (metabolism); Mice, Inbred C57BL; Diet, High-Fat (adverse effects); Rod Opsins (metabolism); Sympathetic Nervous System (metabolism); Adipose Tissue (metabolism); Neurons (metabolism, radiation effects); Adipose Tissue, White (metabolism, radiation effects); Adipocytes, White (metabolism, radiation effects)

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.

First Page

6768

Recommended Citation

Tsuji T, Tolstikov V, Zhang Y, et al. Light-responsive adipose-hypothalamus axis controls metabolic regulation. Nat Commun. 2024;15(1):6768. Published 2024 Aug 8. doi:10.1038/s41467-024-50866-0