Fatty liver without a large “belly”: Magnified review of non-alcoholic fatty liver disease in non-obese patients

Yousef, Mohammad S.; Juboori, Alhareth Al; Albarrak, Abdulmajeed; Ibdah, Jamal A.; Tahan, Veysel

doi:10.4291/wjgp.v8.i3.100

Cited by 29 publications

(25 citation statements)

References 64 publications

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“…However, there are individuals with normal body mass index displaying with metabolic disorders, so called metabolically unhealthy non-obese ones. The non-alcoholic fatty liver disease, a common cause of chronic liver disease in the obese population, has been increasingly reported in the non-obese population (Yousef et al 2017). Based on our present results, we suggest that HTG rats fed FRD could serve as an experimental tool in studying metabolically unhealthy non-obese individuals.…”

Section: Discussionsupporting

confidence: 56%

Effect of metabolic syndrome on neural plasticity and morphology of the hippocampus: correlations of neurological deficits with physiological status of the rat

Gaspárová

Janega²,

Weismann³

et al. 2018

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Fat-rich diet (FRD) triggers health complications like hypertension, dyslipidemia, hyperglycemia, insulin resistance and non-alcoholic fatty liver disease, known as the risk factors of metabolic syndrome (MetS), which may result in neurological deficits. The impact of MetS on neuronal functions and brain morphology are poorly understood. We induced MetS-like conditions by exposing hypertriacylglycerolemic (HTG) rats to FRD for eight weeks with the aim to study possible neurological dysfunctions. HTG-FRD rats were compared to HTG rats and Wistar rats on standard diet. The physiological status of the animals was monitored by body, liver and kidney weight (wt). Morphology of the liver, vessel wall and hippocampus were investigated. Basal neurotransmission and synaptic plasticity were measured in the hippocampus ex-vivo. A marked increase of liver weight with marks of steatosis was found in the HTG-FRD group. FRD induced an increase of aortic intima-media thickness. Extracellular recording revealed FRD-induced impairment of long-term potentiation (LTP) at Cornu Ammonis (CA)3-CA1 synapse, contrary to increased presynaptic fiber volley (pV). Reduced thickness of pyramidal cell layer at the CA1 area was found morphometrically. LTP was directly associated with kidney weight and inversely associated with liver weight, pV directly correlated with liver weight, liver wt/body wt ratio and aortic intima-media thickness. Our results suggest correlations between altered physiological status due to MetS-like conditions and neurological deficits, which may be related with consecutive development of socalled metabolic cognitive syndrome.

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Section: Discussionsupporting

confidence: 56%

Effect of metabolic syndrome on neural plasticity and morphology of the hippocampus: correlations of neurological deficits with physiological status of the rat

Gaspárová

Janega²,

Weismann³

et al. 2018

gpb

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“…Categorizing the NAFLD severity is controversial because of contradicting epidemiological reports. NAFLD in the nonobese population has been increasingly reported, and the pathogenesis of nonobese NAFLD is poorly understood [ 21 ]. It was previously suggested that the long-term prognosis of nonobese NAFLD patients is worse than that of obese NAFLD patients, with a higher mortality rate among nonobese patients, even in those with a normal metabolic profile [ 22 , 23 ].…”

Section: Nonalcoholic Fatty Liver Disease (Nafld) and Lipotoxicitymentioning

confidence: 99%

Hypoxic Signaling and Cholesterol Lipotoxicity in Fatty Liver Disease Progression

Tirosh

2018

Oxidative Medicine and Cellular Longevity

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Cholesterol is the only lipid whose absorption in the gastrointestinal tract is limited by gate-keeping transporters and efflux mechanisms, preventing its rapid absorption and accumulation in the liver and blood vessels. In this review, I explored the current data regarding cholesterol accumulation in liver cells and key mechanisms in cholesterol-induced fatty liver disease associated with the activation of deleterious hypoxic and nitric oxide signal transduction pathways. Although nonalcoholic fatty liver disease (NAFLD) affects both obese and nonobese individuals, the mechanism of NAFLD progression in lean individuals with healthy metabolism is puzzling. Lean NAFLD individuals exhibit normal metabolic responses, implying that liver damage is not associated with impaired metabolism per se and that direct lipotoxic effects are crucial for disease progression. Several redox and oxidant signaling pathways involving cholesterol are at play in fatty liver disease development. These include impairment of the mitochondrial and lysosomal function by cholesterol loading of the inner-cell membranes; formation of cholesterol crystals and hepatocyte degradation; and crown-like structures surrounding degrading hepatocytes, activating Kupffer cells, and evoking inflammation. The current review focuses on the induction of liver inflammation, fibrosis, and steatosis by free cholesterol via the hypoxia-inducible factor 1α (HIF-1α), a main oxygen-sensing transcription factor involved in all stages of NAFLD. Cholesterol loading in hepatocytes can result in chronic HIF-1α activity because of the decreased oxygen availability and excessive production of nitric oxide and mitochondrial reactive oxygen species.

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“…Yet, 86.2% of all patients were not compliant with the recommended strict diets. Although the use of pharmacotherapy in the management of obesity remains controversial, pharmacological agents may be beneficial in the treatment of obese patients with NAFLD, since visceral fat is strongly associated with hepatic steatosis 42 43. Thus, improving hepatic steatosis in obese patients should be the focus for future intervention trials.…”

Section: Discussionmentioning

confidence: 99%

Real-world comorbidities and treatment patterns among patients with non-alcoholic fatty liver disease receiving phosphatidylcholine as adjunctive therapy in Russia

Маев

Самсонов

Пальгова

et al. 2019

BMJ Open Gastroenterol

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ObjectivePrevious research conducted in Russia showed that the number of patients with non-alcoholic fatty liver disease (NAFLD) and associated metabolic comorbidities is large. We conducted an observational study to describe the management of NAFLD in patients with metabolic syndrome in Russia.DesignA total of 2843 adult patients from 174 medical sites across 6 federal districts of Russia with newly diagnosed NAFLD, who had at least one of four comorbidities, namely overweight/obesity, hypertension, type 2 diabetes mellitus, and hypercholesterolaemia, and who received phosphatidylcholine (PPC) as an adjunctive treatment to standard care, were enrolled during 2015–2016.ResultsOverall, 2263 patients (79.6%) had at least two metabolic comorbidities associated with NAFLD; overweight/obesity was the most common comorbidity reported in 2298 patients (80.8%). Simple steatosis was the most frequently identified clinical form of NAFLD, diagnosed in 2128 patients (74.9%). Among hypertensive patients, ACE inhibitors, statins, and sartans were most commonly prescribed. Biguanides were administered in more than half of diabetic patients. In patients with overweight/obesity and hypercholesterolaemia, statins were the most frequently prescribed medications. Almost all patients (2837/2843; 99.8%) were treated with 1.8 g of PPC three times per day. PPC therapy was associated with a 90.5% 6-month compliance rate, high treatment satisfaction, and a favourable safety profile. However, almost 15% of diabetic patients and 40% of overweight/obese patients received no further treatment.ConclusionsIn Russia, patients with newly diagnosed NAFLD represent a population heavily burdened by comorbidities, mainly overweight/obesity and hypercholesterolaemia. A significant part of these patients did not receive a comprehensive pharmacotherapy, highlighting the existing unmet need in the current management of NAFLD patients with metabolic syndrome in Russia.

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Fatty liver without a large “belly”: Magnified review of non-alcoholic fatty liver disease in non-obese patients

Cited by 29 publications

References 64 publications

Effect of metabolic syndrome on neural plasticity and morphology of the hippocampus: correlations of neurological deficits with physiological status of the rat

Effect of metabolic syndrome on neural plasticity and morphology of the hippocampus: correlations of neurological deficits with physiological status of the rat

Hypoxic Signaling and Cholesterol Lipotoxicity in Fatty Liver Disease Progression

Real-world comorbidities and treatment patterns among patients with non-alcoholic fatty liver disease receiving phosphatidylcholine as adjunctive therapy in Russia

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