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A Persistence Detector for Metabolic Network Rewiring in an Animal

ABSTRACT: Biological systems must possess mechanisms that prevent inappropriate responses to spurious environmental inputs. Caenorhabditis elegans has two breakdown pathways for the short-chain fatty acid propionate: a canonical, vitamin B12-dependent pathway and a propionate-shunt that is used when vitamin B12 levels are low. The shunt pathway is kept off when there is sufficient flux through the canonical pathway, likely to avoid generating shunt-specific toxic intermediates. Here, we discover a transcriptional regulatory circuit that activates shunt gene expression upon propionate buildup. The nuclear hormone receptors NHR-10 and NHR-68 function together as a ‘persistence detector’ in a type 1, coherent feed-forward loop with an AND-logic gate to delay shunt activation upon propionate accumulation, and to avoid spurious shunt activation in response to a non-sustained pulse of propionate. Together, our findings identify the first persistence detector in an animal, which transcriptionally rewires propionate metabolism to maintain homeostasis.

ORGANISM(S): Caenorhabditis elegans

PROVIDER: GSE123507 | GEO | 2018/12/08

REPOSITORIES: GEO

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Project description:The fertility of dairy cows is challenged during early lactation and better nutritional strategies need to be developed to address this issue. Combined supplementation of folic acid and vitamin B12 improves energy metabolism in the dairy cow during early lactation. Therefore, the present study was undertaken to explore the effects of this supplement on gene expression in granulosa cells from the dominant follicle during the postpartum period. Multiparous Holstein cows received weekly intramuscular injection of 320 mg folic acid and 10 mg vitamin B12 (treated group) beginning 24 (SD 4) d before calving until 56 d after calving, whereas the control group received saline. The urea plasma concentration was significantly decreased during the pre-calving period, and the concentration of both folate and vitamin B12 were increased in treated animals. Milk production and dry matter intake were not significantly different between the two groups. Plasma concentrations of folates and vitamin B12 were increased in vitamin-treated animals. Daily dry matter intake was not significantly different between the 2 groups before (13.5 kg SE 0.5) and after (23.6 kg SE 0.9) calving. Average energy-corrected milk tended to be greater in vitamin-treated cows, 39.7 (SE 1.4) and 38.1 (SE 1.3) kg/d for treated and control cows, respectively. After calving, average plasma concentration of BHBA tended to be lower in cows injected with the vitamin supplement, 0.47 (SE 0.04) vs. 0.55 (SE 0.03) for treated and control cows, respectively. The ovarian follicle ? 12 mm in diameter was collected by ovarian pick-up after estrus synchronization. Recovered follicular fluid volumes were greater in the vitamin-treated group. A microarray platform was used to investigate the impact of treatment on gene expression of granulosa cells. Lower expression of genes involved in the cell cycle and higher expression of genes associated with granulosa cell differentiation prior to ovulation were observed. Selected candidate genes were analyzed by reverse transcription quantitative polymerase chain reaction. Although the effects of intramuscular injections of folic acid and vitamin B12 on lactational performance and metabolic status of animals were limited, Ingenuity Pathway Analysis of gene expression in granulosa cells suggests a stimulation of cell differentiation in vitamin-treated cows, which may be the result of an increase in LH secretion. Two conditions experiment (Control and Treated). Granulosa cells from the 66h post second PGF2alpha injection. Biological replicates: 3 from each time point. Two technical replicates for each comparison (dye-swap).

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A Persistence Detector for Metabolic Network Rewiring in an Animal

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