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Light-responsive adipose-hypothalamus axis controls metabolic regulation.
Tadataka Tsuji1, Vladimir Tolstikov2, Yang Zhang1
1Section on Integrative Physiology and Metabolism, Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA.
Nature Communications
|August 8, 2024
Summary
Blue light exposure to fat improves metabolic health by activating a brain-fat pathway. This Opsin3-dependent mechanism involves histidine signaling, offering a novel strategy against obesity.
Area of Science:
- Metabolic research
- Neuroendocrinology
- Light biology
Background:
- Mammals utilize light-sensing photoreceptors in multiple organs.
- Opsin3 is notably abundant in adipose tissue, facilitating inter-organ communication, especially with the brain via the sympathetic nervous system (SNS).
Purpose of the Study:
- To investigate the novel light-triggered crosstalk between adipose tissue and the hypothalamus.
- To explore the role of Opsin3 in mediating metabolic responses to light.
Main Methods:
- Direct blue-light exposure to subcutaneous white fat in a high-fat diet model.
- Metabolomic analysis to identify key signaling molecules.
- Investigation of the sympathetic nervous system (SNS) pathway involving histidine and the hypothalamus.
- Cell-autonomous studies on human white adipocytes.
Main Results:
- Blue light exposure to white fat ameliorated diet-induced metabolic dysfunction in an Opsin3-dependent manner.
- Metabolomics revealed increased histidine levels, which activated hypothalamic histaminergic neurons.
- This activation stimulated brown adipose tissue (BAT) through the SNS.
- Blocking histidine's central effects or denervating BAT abolished the benefits of blue light.
- Human white adipocytes demonstrated cell-autonomous responses to blue light.
Conclusions:
- A novel light-responsive metabolic circuit exists between adipose tissue and the hypothalamus.
- This pathway, mediated by Opsin3 and histidine, offers a potential therapeutic strategy for obesity-related metabolic disorders.
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