Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Supplementation of cattle diets with n-3 polyunsaturated fatty acids (n-3 PUFA) has been suggested to have positive effects on fertility. In addition, the actions of the insulin-like growth factor (IGF) system both systemically and locally have been shown to influence reproductive processes. The objective of this study was to evaluate the effect of dietary n-3 PUFA supplementation on hepatic and endometrial expression of IGF signalling genes in cattle. Beef heifers were supplemented with a rumen protected source of either a saturated fatty acid (palmitic acid; CON) or high n-3 PUFA diet (n-3 PUFA) for 45 days before slaughter and tissue recovery. Transcription level of candidate IGF signalling genes was measured by reverse transcription quantitative real-time PCR (RT-qPCR) in total RNA isolated from uterine endometrial and liver tissue from seven CON and seven n-3 PUFA supplemented animals. Compared to controls, mRNA abundance in n-3 PUFA liver tissues was higher for IGF-2R, IGFBP-1 and IGFBP-5 (P < 0.05); lower for GHR-1A (P < 0.05); and unchanged for IGF-1, IGF-2, IGF-1R, IGFBP-2, IGFBP-3, IGFBP-4, IGFBP-6, ALS and GHR(total) (P > 0.05). Compared to controls, mRNA abundance in n-3 PUFA endometrial tissues was higher for IGF-2, IGF-1R, IGF-2R and IGFBP-2 (P < 0.05); lower for IGF-1, IGFBP-3 and IGFBP-6 (P < 0.05); and unchanged for IGFBP-1, IGFBP-4, IGFBP-5 and GHR(total) (P > 0.05). Thus, dietary supplementation of cattle with n-3 PUFA affects transcription of genes involved in IGF signalling, in a tissue dependent fashion.
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PMID:Effect of dietary n-3 polyunsaturated fatty acid supplementation on bovine uterine endometrial and hepatic gene expression of the insulin-like growth factor system. 2111 66

Valosin-containing protein (VCP)-associated disease caused by mutations in the VCP gene includes combinations of a phenotypically heterogeneous group of disorders such as hereditary inclusion body myopathy, Paget's disease of bone, frontotemporal dementia and amyotrophic lateral sclerosis. Currently, there are no effective treatments for VCP myopathy or dementia. VCP mouse models carrying the common R155H mutation include several of the features typical of the human disease. In our previous investigation, VCP(R155H/R155H) homozygous mice exhibited progressive weakness and accelerated pathology prior to their early demise. Herein, we report that feeding pregnant VCP(R155H/+) heterozygous dams with a lipid-enriched diet (LED) results in the reversal of the lethal phenotype in VCP(R155H/R155H) homozygous offspring. We examined the effects of this diet on homozygous and wild-type mice from birth until 9 months of age. The LED regimen improved survival, motor activity, muscle pathology and the autophagy cascade. A targeted lipidomic analysis of skeletal muscle and liver revealed elevations in tissue levels of non-esterified palmitic acid and ceramide (d18:1/16:0), two lipotoxic substances, in the homozygous mice. The ability to reverse lethality, increase survival, and ameliorate myopathy and lipids deficits in the VCP(R155H/R155H) homozygous animals suggests that lipid supplementation may be a promising therapeutic strategy for patients with VCP-associated neurodegenerative diseases.
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PMID:Lipid-enriched diet rescues lethality and slows down progression in a murine model of VCP-associated disease. 2415 50