Splanchnic Balance of Free Fatty Acids, Endocannabinoids, and Lipids in Subjects With Nonalcoholic Fatty Liver Disease

Westerbacka, Jukka; Kotronen, Anna; Fielding, Barbara A.; Wahren, John; Hodson, Leanne; Perttilä, Julia; Seppänen‐Laakso, Tuulikki; Suortti, Tapani; Arola, Johanna; Hultcrantz, Rolf; Castillo, Sandra; Olkkonen, Vesa M.; Frayn, Keith N.; Orešič, Matej; Yki‐Järvinen, Hannele

doi:10.1053/j.gastro.2010.06.064

Cited by 65 publications

(59 citation statements)

References 49 publications

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“…In serum, the relative concentrations of 16:0, 16:1, and 18:0 esterified fatty acids were positively correlated with insulin resistance, and those of essential fatty acids were inversely correlated with insulin resistance (48). Similar data were observed when liver fat was plotted against the splanchnic production rate of TAGs (47). TAGs containing saturated or monounsaturated fatty acids also predominate in liver biopsy samples of subjects with increased compared with normal liver fat content (49).…”

Section: The Pnpla3supporting

confidence: 55%

“…We have previously measured the lipid and fatty acid composition in lipoprotein fractions in subjects who exhibited a broad range of insulin sensitivity (47) and determined the rate of production of individual TAGs across the splanchnic bed in NAFLD subjects (47). In serum, the relative concentrations of 16:0, 16:1, and 18:0 esterified fatty acids were positively correlated with insulin resistance, and those of essential fatty acids were inversely correlated with insulin resistance (48).…”

Section: The Pnpla3mentioning

confidence: 99%

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Circulating Triacylglycerol Signatures in Nonalcoholic Fatty Liver Disease Associated With the I148M Variant in PNPLA3 and With Obesity

et al. 2013

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We examined whether relative concentrations of circulating triacylglycerols (TAGs) between carriers compared with noncarriers of PNPLA3 I148M gene variant display deficiency of TAGs, which accumulate in the liver because of defective lipase activity. We also analyzed the effects of obesity-associated nonalcoholic fatty liver disease (NAFLD) independent of genotype, and of NAFLD due to either PNPLA3 I148M gene variant or obesity on circulating TAGs. A total of 372 subjects were divided into groups based on PNPLA3 genotype or obesity. Absolute and relative deficiency of distinct circulating TAGs was observed in the PNPLA3 148MM/148MI compared with the PNPLA3 148II group. Obese and 'nonobese' groups had similar PNPLA3 genotypes, but the obese subjects were insulinresistant. Liver fat was similarly increased in obese and PNPLA3 148MM/148MI groups. Relative concentrations of TAGs in the obese subjects versus nonobese displayed multiple changes. These closely resembled those between obese subjects with NAFLD but without PNPLA3 I148M versus those with the I148M variant and NAFLD. The etiology of NAFLD influences circulating TAG profiles. 'PNPLA3 NAFLD' is associated with a relative deficiency of TAGs, supporting the idea that the I148M variant impedes intrahepatocellular lipolysis rather than stimulates TAG synthesis. 'Obese NAFLD' is associated with multiple changes in TAGs, which can be attributed to obesity/insulin resistance rather than increased liver fat content per se.

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Section: The Pnpla3supporting

confidence: 55%

Section: The Pnpla3mentioning

confidence: 99%

Circulating Triacylglycerol Signatures in Nonalcoholic Fatty Liver Disease Associated With the I148M Variant in PNPLA3 and With Obesity

et al. 2013

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“…We assume this process also saturates, with associated parameters, v 8 , k 8 . Beta-oxidation of fatty acids has been shown to decrease in response to insulin [60], so we assume a loss of FFA proportional to the amount of FFA at rate k 7 , and at an insulin-inhibited rate k 5 . DNL adds to liver fatty acids at rate k al as previously described.…”

Section: Liver Lipidmentioning

confidence: 99%

“…Parameter is adjusted for insulin inhibition by fitting to experimental data in Westerbacka et al [60]. Note, we assume ketone production is proportional to FFA oxidation.…”

Section: Description Variable Steady Value Referencementioning

confidence: 99%

Mathematical modelling of hepatic lipid metabolism

Pratt

Wattis

Salter

2015

Mathematical Biosciences

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The aim of this paper is to develop a mathematical model capable of simulating the metabolic response to a variety of mixed meals in fed and fasted conditions with particular emphasis placed on the hepatic triglyceride element of the model. Model validation is carried out using experimental data for the ingestion of three mixed composition meals over a 24-hour period. Comparison with experimental data suggests the model predicts key plasma lipids accurately given a prescribed insulin profile. One counter-intuitive observation to arise from simulations is that liver triglyceride initially decreases when a high fat meal is ingested, a phenomenon potentially explained by the carbohydrate portion of the meal raising plasma insulin.

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“…Nel topo alimentato con dieta pro-obesità (DIO), la terapia cronica con rimonabant causava una transitoria riduzione degli introiti alimentari ma veniva registrata una perdita di peso sostenuta, indicando un effetto dimagrante indipendente dal bilancio energetico (60,61). L'aumento de novo della lipogenesi epatica, è stata documentata nel topo DIO (62,63), così come nei soggetti con NAFLD (64,65), e può essere mediata dagli endocannabinoidi. Infatti, in studi condotti nei roditori, l'espressione del gene lipogenico e il tasso di lipogenesi epatica de novo, risultavano aumentati dagli agonisti CB 1 e diminuiti dagli antagonisti (66,67,68,69).…”

Section: Endocannabinoidi E Fibrosi Epaticaunclassified

Che cosa so di... Il ruolo della Cannabis e dei Cannabinoidi nelle malattie del fegato: review della letteratura

Vivo¹,

Bellinato²,

Marucco³

et al. 2017

Mission

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IntroduzioneL'utilizzo della cannabis a scopo terapeutico risale a migliaia di anni prima di Cristo, oggi il suo utilizzo è illegale in quasi tutti i paesi occidentali, ma da anni esiste un forte movimento, attivo soprattutto negli Stati Uniti, a favore della sua reintroduzione anche a scopo ricreativo. Ad oggi, sono 20 Stati e il Distretto di Columbia, ad aver approvato regolamenti che hanno permesso di depenalizzare o legalizzare la produzione e l'uso della cannabis a fini terapeutici. Secondo i dati pubblicati dall'International Narcotics Control Board (Narcotic Drugs: Estimated world requirements for 2015; statistics for 2013), i Paesi produttori di cannabis oltre gli Stati Uniti, sono: Canada, Regno Unito, Olanda, Danimarca, Francia, Romania, Repubblica Ceca e Israele.In Italia con il decreto del 9 novembre 2015, il Ministro della Salute ha rilasciato la concessione delle autorizzazioni per la coltivazione, la produzione, la fabbricazione, l'impiego, il commercio, l'esportazione, l'importazione, il transito, l'acquisto, la vendita e la detenzione delle sostanze stupefacenti o psicotrope prestando particolare attenzione ai medicinali di origine vegetale a base di cannabis. La rimborsabilità a carico del Servizio sanitario regionale prevede che la produzione nazionale di sostanze e preparazioni di origine vegetale a base di cannabis, avvenga presso lo Stabilimento chimico farmaceutico militare di Firenze e sia subordinata alle indicazioni emanate da parte delle Regioni o Province autonome. Le regioni che attualmente hanno approvato l'utilizzo della cannabis a scopo terapeutico sono rappresentate da: Puglia, Toscana, Veneto, Liguria, Marche, Friuli Venezia Giulia, Abruzzo, Sicilia, Umbria, Basilicata, Emilia Romagna, Piemonte e Valle D'Aosta. La prescrizione medica di questi preparati non deve essere considerata una terapia propriamente detta, bensì un trattamento sintomatico di supporto ai trattamenti standard, quando questi ultimi non hanno prodotto gli effetti desiderati, hanno provocato effetti secondari non tollerabili, o necessitano di incrementi posologici che potrebbero determinare la comparsa di effetti collaterali . Mission 46.......................................................................................................................................................................................................... SummaryIn many States of USA and some Italian regions, marijuana has been legalized as medical drug. So, a process of cannabis decriminalization is in place throughout the West. The debate about cannabis goes on politically and socially with contrasting aspects. Both as regards the recreational use, it should be recalled that is considered harmful (to a different extent) by virtually all the experts; both in terms of therapeutic use, considered promising by many researchers, but for which the results really sure still seem limited to a few ambit. This paper provides a review to groped to shed light on this topic both on the legal peculiarities and medical prescribing, and espe...

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Splanchnic Balance of Free Fatty Acids, Endocannabinoids, and Lipids in Subjects With Nonalcoholic Fatty Liver Disease

Cited by 65 publications

References 49 publications

Circulating Triacylglycerol Signatures in Nonalcoholic Fatty Liver Disease Associated With the I148M Variant in PNPLA3 and With Obesity

Circulating Triacylglycerol Signatures in Nonalcoholic Fatty Liver Disease Associated With the I148M Variant in PNPLA3 and With Obesity

Mathematical modelling of hepatic lipid metabolism

Che cosa so di... Il ruolo della Cannabis e dei Cannabinoidi nelle malattie del fegato: review della letteratura

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