Preprint Article Version 1 This version is not peer-reviewed

Liver Transcriptomic Profiles of Ruminant Species Fed Spent Hemp Biomass Containing Cannabinoids

Version 1 : Received: 1 July 2024 / Approved: 2 July 2024 / Online: 2 July 2024 (11:14:56 CEST)

How to cite: Irawan, A.; Bionaz, M. Liver Transcriptomic Profiles of Ruminant Species Fed Spent Hemp Biomass Containing Cannabinoids. Preprints 2024, 2024070226. https://doi.org/10.20944/preprints202407.0226.v1 Irawan, A.; Bionaz, M. Liver Transcriptomic Profiles of Ruminant Species Fed Spent Hemp Biomass Containing Cannabinoids. Preprints 2024, 2024070226. https://doi.org/10.20944/preprints202407.0226.v1

Abstract

The inclusion of spent hemp biomass (SHB), an extracted byproduct from industrial cannabidiol (CBD) production, in the diets of dairy cows and lambs appear to be safe with minor effects on the metabolism, including a decrease of circulating cholesterol and increase bilirubinemia, both associated with liver metabolism. Those effects could be consequence of the presence of cannabinoids, particularly Δ9-tetrahydrocannabinol (THC) and CBD in the SHB. This study aimed to study the transcriptional profile of the liver of dairy cows and lambs fed SHB. Dairy cows received SHB or alfalfa pellet for four weeks of intervention (IP) and four weeks of withdrawal periods (WP). Finishing lambs were fed a control diet (CON), 10% (LH2) or 20% (HH2) SHB for 2 months or 1 month followed by 1-month SHB withdrawal (LH1 and HH1, respectively). RNA sequencing was performed, and the mRNA was annotated using the latest reference genomes. The RNAseq data were filtered, normalized for library size and composition, and statistically analyzed by DESeq2. The bioinformatic analysis was performed by using DAVID, Gene Set Enrichment (GSE) analysis, and the Dynamic Impact Approach. Using a 0.2 FDR cut-off, we identified only ≤24 differentially expressed genes (DEG) in the liver by feeding SHB in dairy cows and a larger number of DEG in lambs (from 71 in HH1 vs. CON to 552 in LH1 vs. CON). The KEGG analysis demonstrated that feeding SHB in dairy cows and lambs had relatively minor to moderate metabolic alterations in dairy cows and lambs mainly associated with amino acids and lipid metabolism whereas cholesterol synthesis was overall activated in lambs. GSE analysis identified activation of PPAR signaling pathway only in dairy cows. We found an opposite effect on activation of metabolism of drug and xenobiotics by cytochrome P450 enzymes in dairy cows and lambs receiving less SHB but an inhibition in HH2 lambs. Immune system-related pathways were inhibited by feeding SHB in lambs, but the impact was minor. Cumulatively, inclusion of SHB containing cannabinoids in dairy and lambs demonstrate very little effects on the alteration of transcriptomic profile of the liver.

Keywords

cannabinoids; CBD; liver; ruminant; THC; transcriptomic.

Subject

Biology and Life Sciences, Agricultural Science and Agronomy

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