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• W3011769929 abstract "Non-alcoholic fatty liver disease (NAFLD), type 2 diabetes (T2D) and obesity are epidemiologically correlated with each other but the causal inter-relationships between them remain incompletely understood. We aimed to explore the causal relationships between the 3 diseases.Using both UK Biobank and publicly available genome-wide association study data, we performed a 2-sample bidirectional Mendelian randomization analysis to test the causal inter-relationships between NAFLD, T2D, and obesity. Transgenic mice expressing the human PNPLA3-I148M isoforms (TghPNPLA3-I148M) were used as an example to validate causal effects and explore underlying mechanisms.Genetically driven NAFLD significantly increased the risk of T2D and central obesity but not insulin resistance or generalized obesity, while genetically driven T2D, body mass index and WHRadjBMI causally increased NAFLD risk. The animal study focusing on PNPLA3 corroborated these causal effects: compared to the TghPNPLA3-I148I controls, the TghPNPLA3-I148M mice developed glucose intolerance and increased visceral fat, but maintained normal insulin sensitivity, reduced body weight, and decreased circulating total cholesterol. Mechanistically, the TghPNPLA3-I148M mice demonstrated decreased pancreatic insulin but increased glucagon secretion, which was associated with increased pancreatic inflammation. In addition, transcription of hepatic cholesterol biosynthesis pathway genes was significantly suppressed, while transcription of thermogenic pathway genes was activated in subcutaneous and brown adipose tissues but not in visceral fat in TghPNPLA3-I148M mice.Our study suggests that lifelong, genetically driven NAFLD causally promotes T2D with a late-onset type 1-like diabetic subphenotype and central obesity; while genetically driven T2D, obesity, and central obesity all causally increase the risk of NAFLD. This causal relationship revealed new insights into how nature and nurture drive these diseases, providing novel hypotheses for disease subphenotyping.Non-alcoholic fatty liver disease, type 2 diabetes and obesity are epidemiologically correlated with each other, but their causal relationships were incompletely understood. Herein, we identified causal relationships between these conditions, which suggest that each of these closely related diseases should be further stratified into subtypes. This is important for accurate diagnosis, prevention and treatment of these diseases." @default.
• W3011769929 created "2020-03-23" @default.
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• W3011769929 date "2020-08-01" @default.
• W3011769929 modified "2023-10-14" @default.
• W3011769929 title "Causal relationships between NAFLD, T2D and obesity have implications for disease subphenotyping" @default.
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• W3011769929 cites W1966549856 @default.
• W3011769929 cites W1972696558 @default.
• W3011769929 cites W2014718725 @default.
• W3011769929 cites W2017511982 @default.
• W3011769929 cites W2023420322 @default.
• W3011769929 cites W2038831349 @default.
• W3011769929 cites W2040471688 @default.
• W3011769929 cites W2069091516 @default.
• W3011769929 cites W2093362931 @default.
• W3011769929 cites W2096694584 @default.
• W3011769929 cites W2100099848 @default.
• W3011769929 cites W2104549677 @default.
• W3011769929 cites W2106379479 @default.
• W3011769929 cites W2110244506 @default.
• W3011769929 cites W2112291880 @default.
• W3011769929 cites W2113699335 @default.
• W3011769929 cites W2145813488 @default.
• W3011769929 cites W2151600164 @default.
• W3011769929 cites W2153118028 @default.
• W3011769929 cites W2153554912 @default.
• W3011769929 cites W2154914594 @default.
• W3011769929 cites W2156760391 @default.
• W3011769929 cites W2158005146 @default.
• W3011769929 cites W2159422401 @default.
• W3011769929 cites W2163904781 @default.
• W3011769929 cites W2164619984 @default.
• W3011769929 cites W2165144879 @default.
• W3011769929 cites W2216671742 @default.
• W3011769929 cites W2291173445 @default.
• W3011769929 cites W2324862792 @default.
• W3011769929 cites W2420486924 @default.
• W3011769929 cites W2478486259 @default.
• W3011769929 cites W2516035326 @default.
• W3011769929 cites W2531231413 @default.
• W3011769929 cites W2555602638 @default.
• W3011769929 cites W2604218568 @default.
• W3011769929 cites W2607779679 @default.
• W3011769929 cites W2609051652 @default.
• W3011769929 cites W2734724639 @default.
• W3011769929 cites W2755166087 @default.
• W3011769929 cites W2756413447 @default.
• W3011769929 cites W2757980641 @default.
• W3011769929 cites W2761141539 @default.
• W3011769929 cites W2765105402 @default.
• W3011769929 cites W2771229928 @default.
• W3011769929 cites W2774874882 @default.
• W3011769929 cites W2780792102 @default.
• W3011769929 cites W2783938573 @default.
• W3011769929 cites W2791409258 @default.
• W3011769929 cites W2795554754 @default.
• W3011769929 cites W2796315256 @default.
• W3011769929 cites W2800258246 @default.
• W3011769929 cites W2803072880 @default.
• W3011769929 cites W2808628069 @default.
• W3011769929 cites W2810852503 @default.
• W3011769929 cites W2891048029 @default.
• W3011769929 cites W2894662039 @default.
• W3011769929 cites W2903278832 @default.
• W3011769929 cites W2904837342 @default.
• W3011769929 cites W2912297426 @default.
• W3011769929 cites W2914775288 @default.
• W3011769929 cites W2915824064 @default.
• W3011769929 cites W2916359422 @default.
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• W3011769929 doi "https://doi.org/10.1016/j.jhep.2020.03.006" @default.
• W3011769929 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7371536" @default.
• W3011769929 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32165250" @default.
• W3011769929 hasPublicationYear "2020" @default.
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