Full text
2,801 characters
· extracted from
oa-doi-fallback
· click to expand
Abstract
Circadian disruption is a pervasive environmental stressor that increases susceptibility to metabolic and inflammatory diseases, yet sex-specific adaptive strategies remain poorly understood. Here, we show that constant light (LL) exposure alters gut microbial communities and triggers sex- and tissue-specific host adaptations in the endocannabinoidome and other bioactive lipids. Using 16S rRNA sequencing, short chain fatty acid (SCFA) quantification, LC-MS/MS lipidomics, and cytokine profiling, we identified divergent coping strategies across brain, metabolic and intestinal tissues and reproductive organs. In females, LL induced microbial restructuring, with enrichment of Rikenellaceae, Butyricicoccaceae, and Alistipes, but these changes were uncoupled from short-chain fatty acids (SCFA) output. Also, they engaged N-acylethanolamine (NAE)-driven endocannabinoidome signaling in the brain (AEA, DHEA, OEA, PEA, SEA), accompanied by omega-6 prostaglandin upregulation and increased cytokines (IL-5, IFN-γ, MIP-2). The 2-monoacyl glycerols (2-MAGs) increased selectively in liver and skeletal muscle, reflecting tissue-specific lipid remodeling. In males, microbial shifts were limited (e.g., Ruminococcaceae depletion, Tuzzerella enrichment), yet LL triggered robust metabolic adaptation resulting in elevated SCFA levels (isobutyric, butyric, isovaleric, valeric acids) in faeces and elevation of several DHA-derived bioactive lipids in different intestinal tissues Few alterations in brain bioactive lipids were found, while several 2-MAGs were elevated skeletal muscles and testes. In contrast, several oxylipins were decreased within subcutaneous but not other adipose tissue depots. Together, the data shows that changes in bioactive lipid levels in response to circadian rhythm disruption are organ- and sex-specific as are alterations in microbiota populations, positioning sex as a key determinant of responses to circadian stress.
Competing Interest Statement
The authors have declared no competing interest.
Abbreviations
- LL
- constant light
- LD
- light/dark
- SCN
- suprachiasmatic nucleus
- SCFA
- short-chain fatty acid
- ECS
- endocannabinoid system
- eCBome
- endocannabinoidome
- NAE
- N-acylethanolamine
- 2-MAG
- 2-monoacylglycerol
- 2-AG
- 2-arachidonoylglycerol
- AEA
- anandamide
- PEA
- N-palmitoyl-ethanolamine
- OEA
- N-oleoyl-ethanolamine
- DHEA
- N-docosahexaenoyl-ethanolamine
- WAT
- white adipose tissue
- BAT
- brown adipose tissue
- DHA
- docosahexaenoic acid
- EPA
- eicosapentaenoic acid
- SDA
- stearidonic acid
- MASLD
- metabolic dysfunction-associated steatotic liver disease
- ZT / CT
- zeitgeber time / circadian time
- GC-FID
- gas chromatography with flame ionization detection
- LC-MS/MS
- liquid chromatography–tandem mass spectrometry.
Text is read by the "Ask this paper" AI Q&A widget below.
Extraction quality varies by source — PMC NXML preserves structure
cleanly, OA-HTML may include some navigation residue, and OA-PDF can
have broken hyphenation. The publisher copy
(via DOI)
is the canonical version.