Dietary n-6 to n-3 fatty acid ratio is related to liver fat content independent of genetic effects: Evidence from the monozygotic co-twin control design

Non-alcoholic fatty liver disease encompasses a spectrum of conditions from hepatic steatosis through to cirrhosis; obesity is a known risk factor. The liver plays a major role in regulating fatty acid metabolism and perturbations in intrahepatic processes have potential to impact on metabolic health. It remains unclear why intra-hepatocellular fat starts to accumulate, but it likely involves an imbalance between fatty acid delivery to the liver, fatty acid synthesis and oxidation within the liver and TAG export from the liver. As man spends the majority of the day in a postprandial rather than postabsorptive state, dietary fatty acid intake should be taken into consideration when investigating why intra-hepatic fat starts to accumulate. This review will discuss the impact of the quantity and quality of dietary fatty acids on liver fat accumulation and metabolism, along with some of the potential mechanisms involved. Studies investigating the role of dietary fat in liver fat accumulation, although surprisingly limited, have clearly demonstrated that it is total energy intake, rather than fat intake per se, that is a key mediator of liver fat content; hyperenergetic diets increase liver fat whilst hypoenergetic diets decrease liver fat content irrespective of total fat content. Moreover, there is now, albeit limited evidence emerging to suggest the composition of dietary fat may also play a role in liver fat accumulation, with diets enriched in saturated fat appearing to increase liver fat content to a greater extent when compared with diets enriched in unsaturated fats.

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Increased Liver Fatty Acid Uptake Is Partly Reversed and Liver Fat Content Normalized After Bariatric Surgery

Diabetes Care ◽

10.2337/dc17-0738 ◽

2017 ◽

Vol 41 (2) ◽

pp. 368-371 ◽

Cited By ~ 14

Author(s):

Heidi Immonen ◽

Jarna C. Hannukainen ◽

Nobuyuki Kudomi ◽

Jussi Pihlajamäki ◽

Virva Saunavaara ◽

...

Keyword(s):

Bariatric Surgery ◽

Fatty Acid ◽

Fatty Acid Uptake ◽

Fat Content ◽

Liver Fat ◽

Acid Uptake ◽

Liver Fatty Acid ◽

Liver Fat Content

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Effect of Weight Loss on Liver Free Fatty Acid Uptake and Hepatic Insulin Resistance

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2008-1689 ◽

2009 ◽

Vol 94 (1) ◽

pp. 50-55 ◽

Cited By ~ 83

Author(s):

Antti P. M. Viljanen ◽

Patricia Iozzo ◽

Ronald Borra ◽

Mikko Kankaanpää ◽

Anna Karmi ◽

...

Keyword(s):

Insulin Resistance ◽

Weight Loss ◽

Fatty Acid ◽

Free Fatty Acid ◽

Fatty Acid Uptake ◽

Fat Content ◽

Liver Fat ◽

Hepatic Insulin Resistance ◽

Acid Uptake ◽

Liver Fat Content

Abstract Objective: Weight loss has been shown to decrease liver fat content and whole-body insulin resistance. The current study was conducted to investigate the simultaneous effects of rapid weight reduction with a very-low-calorie diet on liver glucose and fatty acid metabolism and liver adiposity. Hypothesis: We hypothesized that liver insulin resistance and free fatty acid uptake would decrease after weight loss and that they are associated with reduction of liver fat content. Design: Thirty-four healthy obese subjects (body mass index, 33.7 ± 8.0 kg/m2) were studied before and after a very-low-calorie diet for 6 wk. Hepatic glucose uptake and endogenous glucose production were measured with [18F]fluorodeoxyglucose during hyperinsulinemic euglycemia and fasting hepatic fatty acid uptake with [18F]fluoro-6-thia-heptadecanoic acid and positron emission tomography. Liver volume and fat content were measured using magnetic resonance imaging and spectroscopy. Results: Subjects lost weight (11.2 ± 2.9 kg; P < 0.0001). Liver volume decreased by 11% (P < 0.002), which was partly explained by decreased liver fat content (P < 0.0001). Liver free fatty acid uptake was 26% lower after weight loss (P < 0.003) and correlated with the decrement in liver fat content (r = 0.54; P < 0.03). Hepatic glucose uptake during insulin stimulation was unchanged, but the endogenous glucose production decreased by 40% (P < 0.04), and hepatic insulin resistance by 40% (P < 0.05). Conclusions: The liver responds to a 6-wk period of calorie restriction with a parallel reduction in lipid uptake and storage, accompanied by enhancement of hepatic insulin sensitivity and clearance.

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The dietary monounsaturated to saturated fatty acid ratio modulates the genetic effects of GCKR on serum lipid levels in children

Clinica Chimica Acta ◽

10.1016/j.cca.2015.08.012 ◽

2015 ◽

Vol 450 ◽

pp. 155-161 ◽

Cited By ~ 8

Author(s):

Hye-Ja Lee ◽

Han Byul Jang ◽

Hyo-Jin Kim ◽

Younjhin Ahn ◽

Kyung-Won Hong ◽

...

Keyword(s):

Fatty Acid ◽

Saturated Fatty Acid ◽

Serum Lipid ◽

Genetic Effects ◽

Fatty Acid Ratio ◽

Lipid Levels ◽

Serum Lipid Levels ◽

Acid Ratio ◽

Saturated Fatty Acid Ratio

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Diabetes Remission Clinical Trial (DiRECT)—Plasma Liver Function Tests Reflect Change in Liver Fat Content in Early Type 2 Diabetes

Diabetes ◽

10.2337/db18-1834-p ◽

2018 ◽

Vol 67 (Supplement 1) ◽

pp. 1834-P

Author(s):

SVIATLANA V. ZHYZHNEUSKAYA ◽

AHMAD AL-MRABEH ◽

CARL PETERS ◽

ALISON C. BARNES ◽

KIEREN G. HOLLINGSWORTH ◽

...

Keyword(s):

Type 2 Diabetes ◽

Clinical Trial ◽

Liver Function ◽

Liver Function Tests ◽

Fat Content ◽

Diabetes Remission ◽

Liver Fat ◽

Early Type ◽

Liver Fat Content

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115-LB: Oral Insulin–Induced Reduction in Liver Fat Content in T2DM Patients with Nonalcoholic Steatohepatitis

Diabetes ◽

10.2337/db20-115-lb ◽

2020 ◽

Vol 69 (Supplement 1) ◽

pp. 115-LB

Author(s):

MIRIAM KIDRON ◽

SHARON PERLES ◽

REEM KALOTI ◽

RAMI GHANTOUS ◽

SUHA F. SANDOUKA ◽

...

Keyword(s):

Nonalcoholic Steatohepatitis ◽

Fat Content ◽

Liver Fat ◽

Oral Insulin ◽

Liver Fat Content

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

BMJ Open ◽

10.1136/bmjopen-2020-044237 ◽

2021 ◽

Vol 11 (6) ◽

pp. e044237

Author(s):

Xiaoming Li ◽

Mingfeng Xia ◽

Hui Ma ◽

Yu Hu ◽

Hongmei Yan ◽

...

Keyword(s):

Logistic Regression ◽

Blood Glucose ◽

Density Lipoprotein ◽

Fat Content ◽

Lipoprotein Cholesterol ◽

Liver Fat ◽

Community Based ◽

Liver Fat Content ◽

Cross Sectional ◽

Multivariable Logistic Regression

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 investigated whether liver fat content (LFC) was associated with MA in a normotensive and non-diabetic population.DesignA cross-sectional substudy.SettingsLFC was determined from the hepatic/renal echogenicity ratio at ultrasound. MA was defined as an albumin-to-creatinine ratio (ACR) of 30–300 µg/mg (early- morning urine sample). Multivariable logistic regression and receiver operating characteristic (ROC) curve analyses were used to evaluate LFC as a predictor of MA.ParticipantsBetween May 2010 and June 2011, this cross-sectional, community-based study enrolled residents from Shanghai (China), aged ≥40 years and with normal glucose tolerance and BP.ResultsA total of 550 residents (median age, 57 years; 174 men) were enrolled and stratified according to LFC quartiles. ACR (p<0.001) and MA prevalence (p=0.012) increased across the LFC quartiles. Multivariable logistic regression showed that the OR for MA (per SD increase in LFC) was 1.840 (95% CI 1.173 to 2.887, p=0.008) after adjustment for potential confounders including age, gender, waist-hip ratio, blood urea nitrogen, systolic and diastolic BP, fasting blood glucose, postprandial glucose, low-density lipoprotein-cholesterol, triglycerides, high-density lipoprotein-cholesterol, total cholesterol, estimated glomerular filtration rate and lipid-lowering drugs. The ROC analysis revealed that the optimal LFC cut-off value for predicting MA was 6.82%.ConclusionLFC is independently associated with MA in normotensive, euglycaemic middle-aged and elderly Chinese individuals. Screening for MA in people with NAFLD might facilitate early intervention to minimise kidney disease risk.

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A carbohydrate-reduced high-protein diet improves HbA1c and liver fat content in weight stable participants with type 2 diabetes: a randomised controlled trial

Diabetologia ◽

10.1007/s00125-019-4956-4 ◽

2019 ◽

Vol 62 (11) ◽

pp. 2066-2078 ◽

Cited By ~ 20

Author(s):

Mads J. Skytte ◽

Amirsalar Samkani ◽

Amy D. Petersen ◽

Mads N. Thomsen ◽

Arne Astrup ◽

...

Keyword(s):

Type 2 Diabetes ◽

Randomised Controlled Trial ◽

Controlled Trial ◽

High Protein Diet ◽

Fat Content ◽

Protein Diet ◽

Liver Fat ◽

Liver Fat Content ◽

Randomised Controlled

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Liver steatosis coexists with myocardial insulin resistance and coronary dysfunction in patients with type 2 diabetes

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00604.2005 ◽

2006 ◽

Vol 291 (2) ◽

pp. E282-E290 ◽

Cited By ~ 97

Author(s):

Riikka Lautamäki ◽

Ronald Borra ◽

Patricia Iozzo ◽

Markku Komu ◽

Terho Lehtimäki ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Liver Steatosis ◽

Fat Content ◽

Liver Fat ◽

Liver Fat Content ◽

Artery Disease ◽

Myocardial Insulin Resistance ◽

High Liver

Nonalcoholic fatty liver (NAFL) is a common comorbidity in patients with type 2 diabetes and links to the risk of coronary syndromes. The aim was to determine the manifestations of metabolic syndrome in different organs in patients with liver steatosis. We studied 55 type 2 diabetic patients with coronary artery disease using positron emission tomography. Myocardial perfusion was measured with [15O]H2O and myocardial and skeletal muscle glucose uptake with 2-deoxy-2-[18F]fluoro-d-glucose during hyperinsulinemic euglycemia. Liver fat content was determined by magnetic resonance proton spectroscopy. Patients were divided on the basis of their median (8%) into two groups with low (4.6 ± 2.0%) and high (17.4 ± 8.0%) liver fat content. The groups were well matched for age, BMI, and fasting plasma glucose. In addition to insulin resistance at the whole body level ( P = 0.012) and muscle ( P = 0.002), the high liver fat group had lower insulin-stimulated myocardial glucose uptake ( P = 0.040) and glucose extraction rate ( P = 0.0006) compared with the low liver fat group. In multiple regression analysis, liver fat content was the most significant explanatory variable for myocardial insulin resistance. In addition, the high liver fat group had increased concentrations of high sensitivity C-reactive protein, soluble forms of E-selectin, vascular adhesion protein-1, and intercellular adhesion molecule-1 ( P < 0.05) and lower coronary flow reserve ( P = 0.02) compared with the low liver fat group. In conclusion, in patients with type 2 diabetes and coronary artery disease, liver fat content is a novel independent indicator of myocardial insulin resistance and reduced coronary functional capacity. Further studies will reveal the effect of hepatic fat reduction on myocardial metabolism and coronary function.

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