Circulating phospholipid profiling identifies portal contribution to NASH signature in obesity

Anjani, Kavya; Lhomme, Marie; Sokolovska, Nataliya; Poitou, Christine; Aron‐Wisnewsky, Judith; Bouillot, Jean‐Luc; Lesnik, Philippe; Bédossa, Pierre; Kontush, Anatol; Clément, Karine; Dugail, Isabelle; Tordjman, Joan

doi:10.1016/j.jhep.2014.11.002

Cited by 92 publications

(99 citation statements)

References 40 publications

(37 reference statements)

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“…Increased circulating concentration of ceramides were seen in peripheral blood samples of obese patients with NASH 16 . Ceramides can be produced de novo after oxidative stress from palmitoyl co-A and serine through the action of serine palmitoyl co-A transferase (SPT), which is the rate limiting enzyme.…”

Section: Hepatotoxic Lipidsmentioning

confidence: 95%

Molecular mechanisms of lipotoxicity and glucotoxicity in nonalcoholic fatty liver disease

et al. 2016

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The exposure of hepatocytes to high concentrations of lipids and carbohydrates and the ensuing hepatocellular injury are termed lipotoxicity and glucotoxicity, respectively. A common denominator is metabolic derangement, especially in regards to intracellular energy homeostasis, which is brought on by glucose intolerance and insulin resistance in tissues. In this review, we highlight the lipids and carbohydrates that provoke hepatocyte injury and the mechanisms involved in lipotoxicity and glucotoxicity, including endoplasmic reticulum stress, oxidative stress and mitochondrial impairment. Through upregulation of proteins involved in various pathways including PKR-like ER kinase (PERK), CCAAT/enhancer-binding homologous protein (CHOP), c-Jun NH2-terminal kinase-1 (JNK), Bcl-2 interacting mediator (BIM), p53 upregulated modulator of apoptosis (PUMA), and eventually caspases, hepatocytes in lipotoxic states ultimately undergo apoptosis. The protective role of certain lipids and possible targets for pharmacological therapy are explored. Finally, we discuss the role of high fructose and glucose diets in contributing to organelle impairment and poor glucose transport mechanisms, which perpetuate hyperglycemia and hyperlipidemia by shunting of excess carbohydrates into lipogenesis.

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Section: Hepatotoxic Lipidsmentioning

confidence: 95%

Molecular mechanisms of lipotoxicity and glucotoxicity in nonalcoholic fatty liver disease

et al. 2016

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“…Postsurgery weight loss in NASH improves the level of liver enzymes and lipids, but most of the PG and Cer species remained elevated; meanwhile weight loss partially attenuated NASH-related alterations in systemic PL profiles 1 year after surgery (42,139,143). Analysis of lipids from the hepatic portal system at the time of surgery revealed that PG and PE classes were increased in NASH subjects; moreover, few alterations were noted in adipose tissue lipid efflux (9,10,39). Serum SLs are dysregulated in patients with several chronic liver diseases, suggesting their role in liver damage (44,62,66).…”

Section: Sl Pathways In Diabetes Nafld and Nashmentioning

confidence: 99%

“…Adiponectin secreted from adipocytes promotes insulin sensitivity and decreases inflammation (8,9,29). It stimulates a ceramidase activity that is linked to its two receptors, AdipoR1 and AdipoR2.…”

Section: Sl Pathways In Diabetes Nafld and Nashmentioning

confidence: 99%

“…Portal and systemic PL profiling defined the NASH signature in morbid obesity (9,10,39). Lipidomic analysis showed a reduction of PC in the steatotic liver; however, PC homeostasis is an important factor for alcoholic steatohepatitis (ASH)/NASH.…”

Section: Sl Pathways In Diabetes Nafld and Nashmentioning

confidence: 99%

“…Accumulation of triacylglycerols (TAG), diacylglycerols (DAG), and free cholesterols; elevated lyso-glycerophosphocholines (LPC); and a shift toward more SFAs have been described in NASH (40,138,142). Increased concentration of several glycerophosphocholines (PC), glycerophosphoethanolamines (PE), glycerophosphoinositols, glycerophosphoglycerols (PG), LPC, and Cers were detected in the systemic circulation of NASH patients (9,10,39). In morbid obesity patients stratified for NASH, the PL composition in the portal circulation differs, in which they indicate 78,82).…”

Section: Sl Pathways In Diabetes Nafld and Nashmentioning

confidence: 99%

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Compounds of the sphingomyelin-ceramide-glycosphingolipid pathways as secondary messenger molecules: new targets for novel therapies for fatty liver disease and insulin resistance

Ilan

2016

American Journal of Physiology-Gastrointestinal and Liver Physi

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The compounds of sphingomyelin-ceramide-glycosphingolipid pathways have been studied as potential secondary messenger molecules in various systems, along with liver function and insulin resistance. Secondary messenger molecules act directly or indirectly to affect cell organelles and intercellular interactions. Their potential role in the pathogenesis of steatohepatitis and diabetes has been suggested. Data samples collected from patients with Gaucher's disease, who had high levels of glucocerebroside, support a role for compounds from these pathways as a messenger molecules in the pathogenesis of fatty liver disease and diabetes. The present review summarizes some of the recent data on the role of glycosphingolipid molecules as messenger molecules in various physiological and pathological conditions, more specifically including insulin resistance and fatty liver disease.

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Polycystic ovary syndrome is associated with nonalcoholic steatohepatitis in women of reproductive age

et al. 2022

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Polycystic ovary syndrome (PCOS) occurs in approximately 10% of all reproductive-age women, with over 50% of these patients having imagingconfirmed nonalcoholic fatty liver disease (NAFLD). Whether PCOS increases the risk for more clinically relevant disease, such as nonalcoholic steatohepatitis (NASH), is unclear. Such findings are relevant to prognosticating risk of progressive liver disease in the growing population of young adults with NAFLD. Using weighted discharge data from the United States National Inpatient Sample from 2016 to 2018, we evaluated the association of PCOS with the presence of NASH among reproductive-age women with NAFLD. The association of PCOS with NASH was assessed by logistic regression, adjusting for demographic and comprehensive metabolic comorbidities. Other causes of hepatic steatosis and chronic liver diseases were excluded. Our analysis included 189,440 reproductive-age women with NAFLD, 9415 of whom had PCOS. Of those with PCOS, 1390 (15%) had a distinct code for NASH. Women with PCOS were younger (median age, 33 vs. 40 years; p < 0.001) and more likely to have diabetes (37.0% vs. 34.0%), obesity (83.0% vs. 58.0%), dyslipidemia (26.0% vs. 21.0%), and hypertension (38.0% vs. 35.0%) (all p ≤ 0.01). On adjusted analysis accounting for these metabolic comorbidities, PCOS remained independently associated with an increased prevalence of NASH (adjusted odds ratio, 1.22; 95% confidence interval, 1.05-1.42; p = 0.008). Conclusions: Among reproductive-age women with NAFLD, metabolic risk factors were more common in those with PCOS.Despite adjustment for these metabolic comorbidities, PCOS remained associated with a 22% higher odds of having NASH. These findings support efforts to increase NAFLD screening in young women with PCOS and highlight the potential "head start" in progressive liver disease among young women with PCOS.

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Circulating phospholipid profiling identifies portal contribution to NASH signature in obesity

Cited by 92 publications

References 40 publications

Molecular mechanisms of lipotoxicity and glucotoxicity in nonalcoholic fatty liver disease

Molecular mechanisms of lipotoxicity and glucotoxicity in nonalcoholic fatty liver disease

Compounds of the sphingomyelin-ceramide-glycosphingolipid pathways as secondary messenger molecules: new targets for novel therapies for fatty liver disease and insulin resistance

Polycystic ovary syndrome is associated with nonalcoholic steatohepatitis in women of reproductive age

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