Increased Liver Fat Content Research Articles

Evaluating the efficacy of 8 non-invasive models in predicting MASLD and progression: a prospective study

BackgroundSelecting the optimal non-invasive diagnostic model for MASLD (Metabolic Dysfunction-Associated Steatosis Liver Disease) and steatosis progression is a critical issue given the variety of available models. We aimed to compare the performance of eight clinical prediction models for diagnosing and predicting the progression of hepatic steatosis using MRI-PDFF (Magnetic Resonance Imaging-Derived Proton Density Fat Fraction), and validate the findings with FibroScan and histopathological results.MethodsIn this study, 846 participants were initially enrolled, with 108 undergoing liver biopsy and 706 completing one-year follow-up, including 26 who underwent repeat biopsy. We calculated scores for eight clinical prediction models (FAST, KNAFLD, HSI, FLI, Liver Fat Score, Liver Fat Equation, BAAT, LAP) using collected clinical data and defined steatosis progression as a 30% relative increase in liver fat content (LFC) measured by MRI-PDFF. CAP(Controlled Attenuation Parameter) and LSM (Liver Stiffness Measurement) were obtained by Fibroscan. MRI-PDFF served as the reference standard for evaluating model accuracy, and sensitivity analyses were performed using liver biopsy and Fibroscan results.ResultsAmong the eight clinical models, NAS (nonalcoholic fatty liver disease activity score) showed higher correlation with the FAST and KNAFLD models (r: 0.62 and 0.52, respectively). Among the whole cohort (N = 846), KNAFLD was the best model for predicting different degrees of hepatic steatosis (AUC = 0.84). When the KNAFLD score was above 2.935, LFC was significantly higher (4.4% vs. 19.7%, P < 0.001). After 1 year of follow-up (N = 706), FAST performed best in predicting MASLD progression (AUC = 0.84); with dFAST > -0.02, LFC increased (8.6–10.9%, P < 0.05), mean LSM increased by 0.51 kPa, and with dFAST < -0.02, LFC significantly decreased (11.5–8.5%, P < 0.05), mean LSM and NAS decreased by 0.87 kPa and 0.76, respectively (both P < 0.05).ConclusionsMost models demonstrated good diagnostic and prognostic capabilities for hepatic steatosis, with FAST and KNAFLD showing particular promise as primary non-invasive tools in clinical practice.Trail RegistrationChinese Clinical Trial Registry NO: ChiCTR2100054743, Registered December 26, 2021.

9210 Nephron specific ATP6AP2 knockout reduces renal fat accumulation in mice consuming high fat diet

Abstract Disclosure: S.A. Culver: None. J. Balugo: None. M. Jansen: None. T. Harris: None. H.M. Siragy: None. Diet induced obesity causes increased renal fat accumulation in both humans and mice which contributes to obesity related kidney injury. We have previously shown that mice with nephron specific ATP6AP2 knockout (KO) consuming high fat diet (HFD) are resistant to weight gain due to increased urinary excretion of glucose, albumin, and fatty acids. Magnetic resonance imaging (MRI) is a useful imaging modality for quantifying organ fat content in live animals though there are few reports of its use quantifying fat in murine kidney. We hypothesized that nephron specific ATP6AP2 knockout inhibits renal fat accumulation with HFD and that we would be able to detect this using MRI. Eight-week-old male wild type (WT) or inducible nephron specific ATP6AP2 KO mice underwent either induction with oral doxycycline or received sucrose water as controls before being placed on either normal diet (ND) (12% fat) or HFD (45% fat) for 3 months. Mice were then imaged using a 9.4 Tesla Bruker BioSpin MRI to determine both liver and kidney cortex fat content. The mean weight of WT HFD mice was 36.03 g compared to 29.03 g in WT ND controls. ND fed and HFD fed KO mice weighed 22.74 g and 23.03 g respectively. MRI showed significant 67% (p&amp;lt;0.05) increase in liver fat content in WT HFD compared to WT ND fed controls, confirming the ability of our MRI technique to detect expected differences in organ fat content. In renal cortex, MRI detected a 54% (p&amp;lt;0.05) increase in lipid content for WT HFD mice compared to WT ND controls. Nephron specific ATP6AP2 KO on HFD demonstrated reduced renal cortical lipid content by 36% (p&amp;lt;0.05) compared to WT HFD controls. These results indicate that ATP6AP2 KO is associated with reduced renal fat accumulation that is measurable with in vivo MRI. MRI therefore represents a valuable tool for studying renal sequelae of obesity in live murine models. Future investigation should examine whether ATP6AP2 KO prevents renal lipotoxicity and kidney injury in the setting of obesity. Presentation: 6/3/2024

Sex-specific effects of PNPLA3 I148M.

Metabolic dysfunction-associated steatotic liver disease (MASLD, previously termed NAFLD, nonalcoholic fatty liver disease) is a complex multifactorial disease showing generally higher prevalence and severity in men than in women. With respect to women, men are also more prone to develop metabolic dysfunction-associated steatohepatitis, fibrosis and liver-related complications. Several genetic, hormonal, environmental and lifestyle factors may contribute to sex differences in MASLD development, progression and outcomes. However, after menopause, the sex-specific prevalence of MASLD shows an opposite trend between men and women, pointing to the relevance of oestrogen signalling in the sexual dimorphism of MASLD. The patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene, that encodes a triacylglycerol lipase that plays a crucial role in lipid metabolism, has emerged as a key player in the pathogenesis of MASLD, with the I148M variant being strongly associated with increased liver fat content and disease severity. Recent advances indicate that carrying the PNPLA3 I148M variant can be a risk factor for MASLD especially for women. To elucidate the molecular mechanisms underlying the sex-specific role of PNPLA3 I148M in the development of MASLD, several invitro, exvivo and invivo models have been developed.

Proteomics and Its Combined Analysis with Transcriptomics: Liver Fat-Lowering Effect of Taurine in High-Fat Fed Grouper (Epinephelus coioides).

In order to understand the intervention effect of taurine on liver fat deposition induced by high fat intake in the orange-spotted grouper (Epinephelus coioides), we performed proteomic analysis and association analysis with previously obtained transcriptomic data. Three isoproteic (47% crude protein) diets were designed to contain two levels of fat and were named as the 10% fat diet (10F), 15% fat diet (15F), and 15% fat with 1% taurine (15FT). The 10F diet was used as the control diet. After 8 weeks of feeding, the 15F diet exhibited comparable weight gain, feed conversion ratio, and hepatosomatic index as the 10F diet, but the former increased liver fat content vs. the latter. Feeding with the 15FT diet resulted in an improvement in weight gain and a reduction in feed conversion ratio, hepatosomatic index, and liver fat content compared with feeding the 15F diet. When comparing liver proteomic data between the 15F and 15FT groups, a total of 133 differentially expressed proteins (DEPs) were identified, of which 51 were upregulated DEPs and 82 were downregulated DEPs. Among these DEPs, cholesterol 27-hydroxylase, phosphatidate phosphatase LPIN, phosphatidylinositol phospholipase C, and 6-phosphofructo-2-kinase were further screened out and were involved in primary bile acid biosynthesis, glycerolipid metabolism, the phosphatidylinositol signaling system, and the AMPK signaling pathway as key DEPs in terms of alleviating liver fat deposition of taurine in high-fat fed fish. With the association analysis of transcriptomic and proteomic data through KEGG, three differentially expressed genes (atp1a, arf1_2, and plcd) and four DEPs (CYP27α1, LPIN, PLCD, and PTK2B) were co-enriched into five pathways related to fat metabolism including primary bile acid synthesis, bile secretion, glycerolipid metabolism, phospholipid D signaling, or/and phosphatidylinositol signaling. The results showed that dietary taurine intervention could trigger activation of bile acid biosynthesis and inhibition of triglyceride biosynthesis, thereby mediating the liver fat-lowering effects in high-fat fed orange-spotted grouper. The present study contributes some novel insight into the liver fat-lowering effects of dietary taurine in high-fat fed groupers.

Gene Silencing of Angiopoietin-like 3 (ANGPTL3) Induced De Novo Lipogenesis and Lipid Accumulation in Huh7 Cell Line.

Angiopoietin-like 3 (ANGPTL3) is a hepatokine acting as a negative regulator of lipoprotein lipase (LPL). Vupanorsen, an ANGPTL3 directed antisense oligonucleotide, showed an unexpected increase in liver fat content in humans. Here, we investigated the molecular mechanism linking ANGPTL3 silencing to hepatocyte fat accumulation. Human hepatocarcinoma Huh7 cells were treated with small interfering RNA (siRNA) directed to ANGPTL3, human recombinant ANGPTL3 (recANGPTL3), or their combination. Using Western blot, Oil Red-O, biochemical assays, and ELISA, we analyzed the expression of genes and proteins involved in lipid metabolism. Oil Red-O staining demonstrated that lipid content increased after 48 h of ANGPTL3 silencing (5.89 ± 0.33 fold), incubation with recANGPTL3 (4.08 ± 0.35 fold), or their combination (8.56 ± 0.18 fold), compared to untreated cells. This effect was also confirmed in Huh7-LX2 spheroids. A total of 48 h of ANGPTL3 silencing induced the expression of genes involved in the de novo lipogenesis, such as fatty acid synthase, stearoyl-CoA desaturase, ATP citrate lyase, and Acetyl-Coenzyme A Carboxylase 1 together with the proprotein convertase subtilisin/kexin 9 (PCSK9). Time-course experiments revealed that 6 h post transfection with ANGPTL3-siRNA, the cholesterol esterification by Acyl-coenzyme A cholesterol acyltransferase (ACAT) was reduced, as well as total cholesterol content, while an opposite effect was observed at 48 h. Under the same experimental conditions, no differences in secreted apoB and PCSK9 were observed. Since PCSK9 was altered by the treatment, we tested a possible co-regulation between the two genes. The effect of ANGPTL3-siRNA on the expression of genes involved in the de novo lipogenesis was not counteracted by gene silencing of PCSK9. In conclusion, our in vitro study suggests that ANGPTL3 silencing determines lipid accumulation in Huh7 cells by inducing the de novo lipogenesis independently from PCSK9.

DNA methylation age acceleration contributes to the development and prediction of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is prevalent in the aging society. Despite body weight reduction, the prevalence of NAFLD has been increasing with aging for unknown reasons. Here, we investigate the association of DNA methylation age acceleration, a hallmark of aging, with risk of NAFLD. Genome-wide DNA methylation profiles were measured in 95 participants who developed type 2 diabetes during 4-year follow-up, and 356 randomly sampled participants from Shanghai Changfeng Study. DNA methylation age was calculated using the Horvath’s method, and liver fat content (LFC) was measured using a quantitative ultrasound method. Subjects with highest tertile of DNA methylation age acceleration (≥ 9.5 years) had significantly higher LFC (7.2% vs 3.1%, P = 0.008) but lower body fat percentage (29.7% vs 33.0%, P = 0.032) than those with lowest tertile of DNA methylation age acceleration (< 4.0 years). After adjustment for age, sex, alcohol drinking, cigarette smoking, BMI, waist circumference, and different type blood cell counts, the risk of NAFLD was still significantly increased in the highest tertile group (OR, 4.55; 95% CI, 1.06–19.61). Even in subjects with similar LFC at baseline, DNA methylation age acceleration was associated with higher increase in LFC (4.0 ± 10.7% vs 0.9 ± 9.5%, P = 0.004) after a median of 4-year follow-up. Further analysis found that 6 CpGs of Horvath age predictors were associated with longitudinal changes in LFC after multivariate adjustment and located on genes that might lead to fat redistribution from peripheral adipose to liver. Combination of the key CpG methylation related to liver fat content with conventional risk factors improves the performance for NAFLD prediction.Graphical

Loss of hepatic PPARα in mice causes hypertension and cardiovascular disease.

The leading cause of death in patients with nonalcoholic fatty liver disease (NAFLD) is cardiovascular disease (CVD). However, the mechanisms are unknown. Mice deficient in hepatocyte proliferator-activated receptor-α (PPARα) (PparaHepKO) exhibit hepatic steatosis on a regular chow diet, making them prone to manifesting NAFLD. We hypothesized that the PparaHepKO mice might be predisposed to poorer cardiovascular phenotypes due to increased liver fat content. Therefore, we used PparaHepKO and littermate control mice fed a regular chow diet to avoid complications with a high-fat diet, such as insulin resistance and increased adiposity. After 30 wk on a standard diet, male PparaHepKO mice exhibited elevated hepatic fat content compared with littermates as measured by Echo MRI (11.95 ± 1.4 vs. 3.74 ± 1.4%, P < 0.05), hepatic triglycerides (1.4 ± 0.10 vs. 0.3 ± 0.01 mM, P < 0.05), and Oil Red O staining, despite body weight, fasting blood glucose, and insulin levels being the same as controls. The PparaHepKO mice also displayed elevated mean arterial blood pressure (121 ± 4 vs. 108 ± 2 mmHg, P < 0.05), impaired diastolic function, cardiac remodeling, and enhanced vascular stiffness. To determine mechanisms controlling the increase in stiffness in the aorta, we used state-of-the-art PamGene technology to measure kinase activity in this tissue. Our data suggest that the loss of hepatic PPARα induces alterations in the aortas that reduce the kinase activity of tropomyosin receptor kinases and p70S6K kinase, which might contribute to the pathogenesis of NAFLD-induced CVD. These data indicate that hepatic PPARα protects the cardiovascular system through some as-of-yet undefined mechanism.

Circulating Metabolomic and Lipidomic Signatures Identify a Type 2 Diabetes Risk Profile in Low-Birth-Weight Men with Non-Alcoholic Fatty Liver Disease

The extent to which increased liver fat content influences differences in circulating metabolites and/or lipids between low-birth-weight (LBW) individuals, at increased risk of type 2 diabetes (T2D), and normal-birth-weight (NBW) controls is unknown. The objective of the study was to perform untargeted serum metabolomics and lipidomics analyses in 26 healthy, non-obese early-middle-aged LBW men, including five men with screen-detected and previously unrecognized non-alcoholic fatty liver disease (NAFLD), compared with 22 age- and BMI-matched NBW men (controls). While four metabolites (out of 65) and fifteen lipids (out of 279) differentiated the 26 LBW men from the 22 NBW controls (p ≤ 0.05), subgroup analyses of the LBW men with and without NAFLD revealed more pronounced differences, with 11 metabolites and 56 lipids differentiating (p ≤ 0.05) the groups. The differences in the LBW men with NAFLD included increased levels of ornithine and tyrosine (PFDR ≤ 0.1), as well as of triglycerides and phosphatidylcholines with shorter carbon-chain lengths and fewer double bonds. Pathway and network analyses demonstrated downregulation of transfer RNA (tRNA) charging, altered urea cycling, insulin resistance, and an increased risk of T2D in the LBW men with NAFLD. Our findings highlight the importance of increased liver fat in the pathogenesis of T2D in LBW individuals.

Abstract P621: Visceral Adipose Tissue Attenuation: A Marker of Liver Fat Content Beyond the Body Mass Index and Visceral Adipose Tissue Area

Introduction: Body mass index (BMI) and visceral adiposity cannot fully discriminate individuals at risk of presenting non-alcoholic fatty liver. Discordant visceral adiposity/liver fat phenotypes highlight the need for a better understanding of mechanisms involved in liver fat (LF) accumulation independent of BMI and visceral adipose tissue (VAT) quantity. Hypothesis: As VAT attenuation is a marker of VAT quality, we hypothesized that this marker would be an important determinant of LF accumulation and that a lower VAT attenuation would be associated with an increased LF accumulation irrespective of BMI and VAT area. Methods: Analyses included 3002 participants (51% men) aged 40 to 70 years with BMI values between 18.5 and 40.0 kg/m 2 of INSPIRE ME-IAA, a prospective observational study conducted in 29 countries in America, Asia, and Europe. Computed tomography was used to measure subcutaneous adipose tissue (SAT) and VAT area and attenuation (a marker of adipocyte size) and liver attenuation (a marker of LF content). Participants’ cardiometabolic health profile was assessed in the fasting state. Partial Pearson correlation coefficients were computed to document the associations between VAT area and attenuation and liver attenuation. Multivariable regression analyses were performed to quantify the contribution of SAT and VAT area and attenuation to LF attenuation. A mixed-model ANOVA was used to compare liver attenuation according to VAT area and attenuation, and to compare VAT attenuation according to LF level and VAT area. A generalized linear mixed model was used to compare the prevalence of type 2 diabetes according to LF content and VAT area. Results: VAT attenuation was associated with liver attenuation in women (r=0.34, p&lt;0.0001; r=0.38, p&lt;0.0001; r=0.36, p&lt;0.0001) and men (r=0.42, p&lt;0.0001; r=0.30, p&lt;0.0001; r=0.24, p&lt;0.0001) within each BMI category (normal weight, overweight, obesity), respectively. VAT attenuation better explained LF attenuation than SAT and VAT area. A low VAT attenuation was associated with a lower liver attenuation within each VAT area tertile in all BMI categories (p&lt;0.05). Furthermore, an increased LF content was associated with a lower VAT attenuation (p&lt;0.05) independent of SAT and VAT area in both sexes in all BMI categories. An increased LF content was also associated with a higher prevalence of type 2 diabetes (p&lt;0.05) in individuals with normal weight and overweight beyond VAT area. Conclusion: A low VAT attenuation reflecting larger adipocytes is associated with an increased LF content and risk of type 2 diabetes independent of BMI and VAT area. These results suggest that VAT attenuation as a marker of adipose tissue quality might be involved in the development of non-alcoholic fatty liver disease.

Neonatal Orally Administered Zingerone Attenuates Alcohol-Induced Fatty Liver Disease in Experimental Rat Models.

Alcohol intake at different developmental stages can lead to the development of alcohol-induced fatty liver disease (AFLD). Zingerone (ZO) possess hepato-protective properties; thus, when administered neonatally, it could render protection against AFLD. This study aimed to evaluate the potential long-term protective effect of ZO against the development of AFLD. One hundred and twenty-three 10-day-old Sprague-Dawley rat pups (60 males; 63 females) were randomly assigned to four groups and orally administered the following treatment regimens daily during the pre-weaning period from postnatal day (PND) 12-21: group 1-nutritive milk (NM), group 2-NM +1 g/kg ethanol (Eth), group 3-NM + 40 mg/kg ZO, group 4-NM + Eth +ZO. From PND 46-100, each group from the neonatal stage was divided into two; subgroup I had tap water and subgroup II had ethanol solution as drinking fluid, respectively, for eight weeks. Mean daily ethanol intake, which ranged from 10 to 14.5 g/kg body mass/day, resulted in significant CYP2E1 elevation (p < 0.05). Both late single hit and double hit with alcohol increased liver fat content, caused hepatic macrosteatosis, dysregulated mRNA expression of SREBP1c and PPAR-α in male and female rats (p < 0.05). However, neonatal orally administered ZO protected against liver lipid accretion and SREBP1c upregulation in male rats only and attenuated the alcohol-induced hepatic PPAR-α downregulation and macrosteatosis in both sexes. This data suggests that neonatal orally administered zingerone can be a potential prophylactic agent against the development of AFLD.

Combined exposure to PM2.5 and high-fat diet facilitates the hepatic lipid metabolism disorders via ROS/miR-155/PPARγ pathway.

Environmental fine particulate matter (PM2.5), which has attracted worldwide attention, is associated with the progression of metabolic-associated fatty liver disease (MAFLD). However, it is unclear whether dietary habit exacerbate liver damage caused by PM2.5. The current study aimed to investigate the combined negative effects of PM2.5 and high-fat diet (HFD) on liver lipid metabolism in C57BL/6J mice. Histopathological and Oil-Red O staining analysis illustrated that PM2.5 exposure resulted in increased liver fat content in HFD-fed C57BL/6J mice, but not in standard chow diet (STD)-fed mice. And there was a synergistic effect between PM2.5 and HFD on hepatic lipotoxicity. The increased ROS levels and augmented oxidative damage were evaluated in liver tissue of mice treated with PM2.5 and HFD together. In addition, excessive ROS production could activate the miR-155/peroxisome proliferator-activated receptor gamma (PPARγ) pathway, including up-regulation of lipid accumulation-related protein expressions of recombinant liver X receptor alpha (LXRα), sterol regulatory element binding protein-1 (SREBP-1), stearoyl-CoA desaturase-1 (SCD1), fatty acid synthase (FAS) and acetyl-CoA carboxylase 1 (ACC1).The use of miR-155 inhibitors demonstrated the indispensable role of miR-155 in the activation of lipid-regulated proteins by PM2.5 and palmitic acid (PA). Collectively, altering high-fat dietary habits could protect against MAFLD motivated by air pollution, and miR-155 might be an effective preventive and therapeutic target for this process.

Rapamycin did not prevent the excessive exercise-induced hepatic fat accumulation

AimsThe excessive eccentric exercise led to hepatic fat accumulation, which occurred concomitantly with elevation in the mammalian target of the rapamycin complex 1 (mTORC1) and insulin signaling pathways. Since mTORC1 and insulin can inhibit the autophagy pathway and explain the liver lipid content elevation, the main objective of the present investigation was to verify the responses of genes and proteins related to the autophagy and lipogenesis pathways in the hepatic tissue of mice submitted to the excessive downhill running protocol with and without rapamycin administration, a drug able to inhibit the mTORC1 pathway. Main methodsC57BL/6J mice were divided into four experimental groups: Control (CT; sedentary), Excessive exercise in downhill running (EE), Excessive exercise in downhill running with chronic administration of rapamycin (EE/Rapa), and Endurance exercise (END). At the end of the protocols, the blood and liver were collected for serum analysis, histology, immunohistochemistry, hepatic fat content, reverse transcription-quantitative polymerase chain reaction, and immunoblotting. Key findings1) higher levels of glucose, insulin, HOMA-IR, cortisol, ALT, and cholesterol, but lower levels of T4 for the EE/Rapa group; 2) hepatic fat accumulation for the EE and EE/Rapa groups; 3) upregulation of LC3 immunoexpression and downregulation of autophagic flux index for the EE and EE/Rapa groups; 4) reduction of P70S6K phosphorylation and SQSTM1 and increase of FOXO1A phosphorylation for the EE/Rapa group. SignificanceThe excessive exercise in downhill running with or without rapamycin led to increased liver fat content. Although rapamycin was effective in inhibiting mTORC1, the autophagy flux was not upregulated.

Increased liver fat associates with severe metabolic perturbations in low birth weight men.

Ectopic liver fat deposition, resulting from impaired subcutaneous adipose tissue expandability, may represent an age-dependent key feature linking low birth weight (LBW) with increased risk of type 2 diabetes (T2D). We examined whether presumably healthy early middle-aged, non-obese LBW subjects exhibit increased liver fat content, whether increased liver fat in LBW is associated with the severity of dysmetabolic traits and finally whether such associations may be confounded by genetic factors. Using 1H magnetic resonance spectroscopy, we measured hepatic fat content in 26 early middle-aged, non-obese LBW and 22 BMI-matched normal birth weight (NBW) males. Endogenous glucose production was measured by stable isotopes, and a range of plasma adipokine and gut hormone analytes were measured by multiplex ELISA. Genetic risk scores were calculated from genome-wide association study (GWAS) data for birth weight, height, T2D, plasma cholesterol and risk genotypes for non-alcoholic fatty liver disease (NAFLD). The LBW subjects had significantly increased hepatic fat content compared with NBW controls (P= 0.014), and 20% of LBW vs no controls had overt NAFLD. LBW subjects with NAFLD displayed widespread metabolic changes compared with NBW and LBW individuals without NAFLD, including hepatic insulin resistance, plasma adipokine and gut hormone perturbations as well as dyslipidemia. As an exception, plasma adiponectin levels were lower in LBW subjects both with and without NAFLD as compared to NBW controls. Genetic risk for selected differential traits did not differ between groups. Increased liver fat content including overt NAFLD may be on the critical path linking LBW with increased risk of developing T2D in a non-genetic manner.

Association between thyroid function and assessment of hepatic fat and iron contents by magnetic resonance imaging

The associations of thyroid function parameters with non-alcoholic fatty liver disease (NAFLD) and hepatic iron overload are not entirely clear. We have cross-sectionally investigated these associations among 2734 participants of two population-based cross-sectional studies of the Study of Health in Pomerania. Serum levels of thyroid-stimulating hormone (TSH), free tri-iodothyronine (fT3), and free thyroxine (fT4) levels were measured. Liver fat content (by proton-density fat fraction) as well as hepatic iron content (by transverse relaxation rate; R2*) were assessed by quantitative MRI. Thyroid function parameters were associated with hepatic fat and iron contents by median and logistic regression models adjusted for confounding. There were no associations between serum TSH levels and liver fat content, NAFLD, or hepatic iron overload. Serum fT4 levels were inversely associated with liver fat content, NAFLD, hepatic iron contents, and hepatic iron overload. Serum fT3 levels as well as the fT3 to fT4 ratio were positively associated with hepatic fat, NAFLD, hepatic iron contents, but not with hepatic iron overload. Associations between fT3 levels and liver fat content were strongest in obese individuals, in which we also observed an inverse association between TSH levels and NAFLD. These findings might be the result of a higher conversion of fT4 to the biologically active form fT3. Our results suggest that a subclinical hyperthyroid state may be associated with NAFLD, particularly in obese individuals. Furthermore, thyroid hormone levels seem to be more strongly associated with increased liver fat content compared to hepatic iron content.

Hepatic venous diameter and liver volume index reflects extent of hepatic steatosis; a population-based study from healthy liver donors

Background and Aim: Nonalcoholic fatty liver disease (NAFLD) has emerged as the most prevalent chronic liver disease in recent years. Further, steatosis is a common finding encountered in living related liver transplant donors (LDLT) during their presurgical evaluation. We have observed that increased liver fat content in donors was associated with relatively smaller hepatic venous diameters. This study was designed to evaluate whether there is a correlation between hepatic venous diameter and liver fat content and whether this would result in a predictive index for hepatic steatosis based on diameters, and liver volume.

Disease activity in inflammatory bowel disease patients is associated with increased liver fat content and liver fibrosis during follow-up.

Liver steatosis is a frequently reported condition in patients with inflammatory bowel disease (IBD). Different factors, both metabolic and IBD-associated, are believed to contribute to the pathogenesis. The aim of our study was to calculate the prevalence of liver steatosis and fibrosis in IBD patients and to evaluate which factors influence changes in steatosis and fibrosis during follow-up. From June 2017 to February 2018, demographic and biochemical data was collected at baseline and after 6-12months. Measured by transient elastography (FibroScan), liver steatosis was defined as Controlled Attenuation Parameter (CAP) ≥248 and fibrosis as liver stiffness value (Emed) ≥7.3kPa. IBD disease activity was defined as C-reactive protein (CRP) ≥10mg/l and/or fecal calprotectin (FCP) ≥150μg/g. Univariate and multivariate regression analysis was performed; a p-value of ≤0.05 was considered significant. Eighty-two out of 112 patients were seen for follow-up; 56% were male. The mean age was 43 ± 16.0years, and mean BMI was 25.1 ± 4.7kg/m2. The prevalence of liver steatosis was 40% and of fibrosis was 20%. At baseline, 26 patients (32%) had an active episode of IBD. Using a multivariate analysis, disease activity at baseline was associated with an increase in liver steatosis (B = 37, 95% CI 4.31-69.35, p = 0.027) and liver fibrosis (B = 1.2, 95% CI 0.27-2.14, p = 0.016) during follow-up. This study confirms the relatively high prevalence of liver steatosis and fibrosis in IBD patients. We demonstrate that active IBD at baseline is associated with both an increase in liver steatosis and fibrosis during follow-up.

Liraglutide Decreases Liver Fat Content and Serum Fibroblast Growth Factor 21 Levels in Newly Diagnosed Overweight Patients with Type 2 Diabetes and Nonalcoholic Fatty Liver Disease.

Purposes In this study, we aimed to verify plasma fibroblast growth factor 21 (FGF21) elevation in newly diagnosed overweight patients with type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD) and to evaluate the effectiveness of liraglutide on reducing liver fat content and serum (FGF21) levels in those patients. Methods A 12-week, single-center, prospective study was conducted. Twenty newly diagnosed overweight patients with T2DM and NAFLD were recruited. Twenty healthy age, sex, and body mass index (BMI) matched subjects were enrolled as the control group. Enzyme-linked immunosorbent assay was used to measure serum FGF21 levels. Liver fat content was determined using the 3.0 T whole-body MRI scanner. Results Those newly diagnosed overweight patients with T2DM and NAFLD had a BMI of 27.6 ± 0.5 kg/m2. They had higher levels of FGF21 (159.6 ± 35.7 vs. 124.1 ± 42.9 pg/ml, P < 0.001) and increased liver fat content (19.3 ± 9.4 vs. 4.5 ± 0.6%, P < 0.001) compared to the controls. Liraglutide treatment for 12 weeks induced a significant 4.9 kg weight loss (95% confidence interval (CI): -6.1, -3.7, P < 0.001), which was equivalent to a relative reduction of 6.8% (95% CI: 5.3%, 8.3%, P < 0.001). FGF21 levels decreased after the 12-week liraglutide treatment (159.6 ± 35.7 vs. 124.2 ± 27.8 pg/ml, P = 0.006). There was a positive correlation between relative changes of liver fat content and relative change of FGF21 (r = 0.645, P = 0.002). FGF21 levels significantly decreased in patients who had a significant decrease in liver fat content (≥29%) (95% CI: -262.8, -55.1, P = 0.006); however, there was no significant change in the patients without a significant decrease in liver fat content (<29%) (95% CI: -60.0, 54.1, P = 0.899). Conclusions Liraglutide treatment reduced both liver fat content and FGF21 levels in newly diagnosed overweight patients with T2DM and NAFLD. FGF21 may be a potential biomarker for evaluating the effects of liraglutide treatment on hepatic fat and glucose metabolism.

Liver fat content is independently associated with microalbuminuria in a normotensive, euglycaemic Chinese population: a community-based, cross-sectional study

ObjectiveNon-alcoholic fatty liver disease (NAFLD) is associated with microalbuminuria (MA) in patients with diabetes/pre-diabetes. Whether this association is mediated by blood glucose and blood pressure (BP) remains unclear. This study...

P184 Disease activity in Inflammatory Bowel Disease patients is associated with increased liver fat content during follow-up

Abstract Background Increased liver steatosis is a frequently reported condition in patients with Inflammatory Bowel Disease (IBD). Different factors, both metabolic and IBD-associated, are believed to be contribute to the pathogenesis. The aim of our study was to calculate the prevalence of liver steatosis (LS) and fibrosis (LF) in IBD patients and evaluate which factors influence changes in steatosis and fibrosis during follow-up. Methods From June 2017 to February 2018, consecutive adult IBD patients were enrolled. Demographic and bio-chemical data were collected at baseline and after 6 to 12 months. The degree of LS and LF was assessed by transient elastography (Fibroscan). LS was defined as a Controlled Attenuation Parameter (CAP) ≥248, LF as a liver stiffness value (Emed) ≥7.3 kPa and IBD disease activity as C-reactive protein (CRP) ≥10 mg/l and/or fecal calprotectin (FCP) ≥150 μg/g. Changes in LS and LF were studied using ∆CAP and ∆Emed (follow-up minus baseline). An independent sample T-test was used to analyze the mean change in ∆CAP and ∆Emed. Univariate and multivariate linear regression analyses were performed, a P-value of ≤0.05 was considered significant. Results A total of 117 IBD patients were enrolled, of which 86 patients were also seen for follow-up. Of these 86 patients, 57% were male with a mean age of 43 (16.1) years. 48% of the patients suffered from Crohn’s disease. The mean Body Mass Index (BMI) was 25.0 (4.7) kg/m2 and 28 patients (33%) had an active episode of IBD at enrollment. The prevalence of LS at baseline was 39%, the prevalence of LF at baseline 13%. The mean change in ∆CAP was 22.44 (75.7) in patients with active disease at baseline and -34.1 (67.5) in patients in remission at baseline (p=0.001). The mean change in ∆Emed was 0.40 (1.9) in patients with active disease at baseline and -0.53 (2.7) in patients in remission at baseline (p=0.075).). Using a multivariate analysis, disease activity at baseline (B=37, 95%CI 6.38–67.61,P=0.018) and LS at baseline (B=-0.4, 95%CI -0.64 – -0.23,P=0.000) were associated with an increase in LS during follow-up. In univariate analyses, no factors associated with LF during follow-up were found. Conclusion Our study reveals a high prevalence of liver steatosis and liver fibrosis in IBD patients. Active IBD at baseline was associated with an increase in liver steatosis during follow up, but not with an increase in liver fibrosis.

Implications of Abdominal Adipose Tissue Distribution on Nonalcoholic Fatty Liver Disease and Metabolic Syndrome: A Chinese General Population Study.

INTRODUCTION:Visceral adipose tissue (VAT) has been found to play a critical role in the development of metabolic syndrome and nonalcoholic fatty liver disease (NAFLD) independent of generalized obesity.METHODS:In this secondary study of prospectively acquired data, 625 participants underwent magnetic resonance spectroscopy and chemical shift fat–water separation MRI (2-point Dixon) of the liver and whole abdomen, respectively, in a 3 Tesla magnet. Whole abdominal VAT and subcutaneous adipose tissue (SAT) were extracted from the 2-point Dixon image series using an automated method. Clinical/anthropometric/blood biochemistry parameters were measured. Using region-specific body mass index, participants were classified into 3 paired subgroups (lean, overweight, and obese) and presence of NAFLD (liver fat content ≥ 5.5%).RESULTS:All relevant clinical/anthropometric/blood biochemistry characteristics and liver enzymes were statistically significant between groups (P < 0.001). NAFLD was found in 12.1%, 43.8%, and 68.3% and metabolic syndrome in 51.1%, 61.9%, and 65% of the lean, overweight, and obese, respectively. Odds ratio for metabolic syndrome and NAFLD was increased by 2.73 (95% confidence interval [CI] 2.18–3.40) and 2.53 (95% CI 2.04–3.12), respectively, for 1SD increase in VAT volume while prevalence of metabolic syndrome was increased by 2.26 (95% CI 1.83–2.79) for 1SD increase in liver fat content (%). VAT/SAT ratio in the lean with fatty liver showed the highest ratio (0.54) among all the subgroups, without a significant difference between the lean and obese with NAFLD (P = 0.127).DISCUSSION:Increased VAT volume/disproportional distribution of VAT/SAT may be vital drivers to the development of metabolic syndrome and NAFLD irrespective of body mass index category.