Dataset Information

Multi-omic profiles of human nonalcoholic fatty liver disease tissue highlight heterogenic phenotypes

ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) is a consequence of sedentary life style and high fat diets with an estimated prevalence of about 30% in western countries. It is associated with insulin resistance, obesity, glucose intolerance and drug toxicity. Additionally, polymorphisms in, e.g. APOC3, PNPLA3, NCAN and PPP1R3B, correlate with NAFLD. Several studies have already investigated later stages of the disease. This study characterizes and stratifies distinct grades of the early steatosis stages of the disease with the aim of identifying mechanisms underlying the etiology of the disease. We analyzed liver biopsies and serum samples from patients with distinct grades of steatosis (also pre-disease states) employing transcriptomics, serum biomarkers, metabolomics, and proteomics. We unveiled distinct transcriptome, proteome and metabolome profiles in patients with high-grade and low-grade steatosis. In line with previously reported causes of steatosis and insulin resistance our observed expression differences in the levels of cytokines, in the IGF-axis, in fat metabolism and branched chain amino acids provide a comprehensive image of the deregulated biological system underlying the disease.

OTHER RELATED OMICS DATASETS IN: PRJNA198657

INSTRUMENT(S): Bruker

SUBMITTER: Ewa Gralka

PROVIDER: MTBLS174 | MetaboLights | 2015-12-07

REPOSITORIES: MetaboLights

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Dataset's files

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			Action	DRS
	MTBLS174	Other
	FILES	Other
	a_MTBLS174_hna_fld_metabolite_profiling_NMR_spectroscopy.txt	Txt
	i_Investigation.txt	Txt
	m_MTBLS174_hna_fld_metabolite_profiling_NMR_spectroscopy_v2_maf.tsv	Tabular

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Publications

Multi-omic profiles of human non-alcoholic fatty liver disease tissue highlight heterogenic phenotypes.

Wruck Wasco W Kashofer Karl K Rehman Samrina S Daskalaki Andriani A Berg Daniela D Gralka Ewa E Jozefczuk Justyna J Drews Katharina K Pandey Vikash V Regenbrecht Christian C Wierling Christoph C Turano Paola P Korf Ulrike U Zatloukal Kurt K Lehrach Hans H Westerhoff Hans V HV Adjaye James J

Scientific data 20151208

Non-alcoholic fatty liver disease (NAFLD) is a consequence of sedentary life style and high fat diets with an estimated prevalence of about 30% in western countries. It is associated with insulin resistance, obesity, glucose intolerance and drug toxicity. Additionally, polymorphisms within, e.g., APOC3, PNPLA3, NCAN, TM6SF2 and PPP1R3B, correlate with NAFLD. Several studies have already investigated later stages of the disease. This study explores the early steatosis stage of NAFLD with the aim ...[more]

PMID: 26646939

Similar Datasets

Project description:Non-alcoholic fatty liver disease (NAFLD) is becoming increasingly common and is a leading cause of end stage liver diseases such as cirrhosis and hepatocellular carcinoma. The rise in NAFLD closely parallels the global epidemic of obesity and type 2 diabetes mellitus (T2DM), and there is a clear interrelationship between abnormal lipid metabolism, insulin resistance, and NAFLD progression. Several genetic loci have been identified as contributors to NAFLD progression, all of which are consistently linked to abnormal lipid metabolic processes in the liver. The common loss-of-function variant rs641738 (C>T) near the gene encoding Membrane_x0002_Bound O-Acyltransferase 7 (MBOAT7) is associated with increased susceptibility to NAFLD as well as the entire spectrum of NAFLD progression. The MBOAT7 gene encodes a lipid metabolic enzyme that is capable of esterifying polyunsaturated fatty acyl-CoAs to LPI substrates to generate phosphatidylinositol (PI) lipids. We previously showed that antisense oligonucleotide (ASO)-mediated knockdown of Mboat7 in mice promoted high fat diet-induced hepatic steatosis, hyperinsulinemia, and systemic insulin resistance (Helsley et al., 2019). Thereafter, other groups showed that hepatocyte-specific genetic deletion of Mboat7 promoted striking fatty liver and NAFLD progression but does not alter insulin sensitivity, suggesting the potential for cell autonomous roles. Here, we show that MBOAT7 function in adipocytes contributes to diet- 3 induced metabolic disturbances including hyperinsulinemia and systemic insulin resistance. The expression of Mboat7 in white adipose tissue closely correlates with diet-induced obesity across a panel of ~100 inbred strains of mice fed a high fat/high sucrose diet. Moreover, adipocyte_x0002_specific genetic deletion of Mboat7 is sufficient to promote hyperinsulinemia, systemic insulin resistance, and mild fatty liver. Unlike in the liver, where Mboat7 plays a relatively minor role in maintaining arachidonic acid (AA)-containing PI pools, Mboat7 is the major source of AA_x0002_containing PI pools in adipose tissue. Our data demonstrate that MBOAT7 is a critical regulator of adipose tissue PI homeostasis, and adipocyte MBOAT7-driven PI biosynthesis is closely linked to hyperinsulinemia and insulin resistance in mice.