Basic and clinical science posters: Lipids and fatty liver

Basic and clinical science posters: Lipids and fatty liver P106 Diabetes Remission Clinical Trial (DiRECT): Does hepatic very low density lipoprotein (VLDL) production determine intrapancreatic fat in Type 2 diabetes?A AL‐MRABEH1, SV Zhyzhneuskaya1, C Peters1, AC Barnes2, B Aribisala3, KG Hollingsworth1, H Pilkington4, MEJ Lean5, R Taylor11Magnetic Resonance Centre, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK, 2Human Nutrition Research Centre, Institute of Health and Society, Newcastle University, Newcastle upon Tyne, UK, 3Computer Science Department, Faculty of Science, Lagos State University, Lagos, Nigeria, 4Clinical Ageing Research Unit, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, UK, 5School of Medicine, Dentistry and Nursing, Royal Infirmary, University of Glasgow, Glasgow, UKRefer to Oral number A77P107The adipokine and hepatokine ANGPTL4 is linked to the pathogenesis of fatty liver disease in obesityL McCulloch1, B Knight2, K KOS11Diabetes and Obesity Research Group, University of Exeter, Exeter, UK, 2Exeter National Institute for Health Research (NIHR) Clinical Research Facility, Royal Devon and Exeter NHS Foundation Trust, Exeter, UKAims: Non‐alcoholic liver disease (NAFLD) is a result of ectopic fat distribution which is frequently found in bariatric patients. Rodent studies suggest that the angiopoietin‐like 4 protein ANGPLT4 which is secreted by adipose tissue and the liver promotes lipolysis and may improve hepatic insulin resistance. We postulate that ANGPLT4 plays a role in the adipose‐liver crosstalk linking adipose tissue dysfunction with NAFLD.Methods: Men and women undergoing elective bariatric surgery were recruited to have biopsies of the right and left liver lobe, omental (OMAT) and abdominal subcutaneous tissue (SCAT) and muscle during surgery. A repeated SCAT biopsy was obtained at nine‐month follow‐up. NASH score was defined by histological examination. Transcriptomic signatures of ECM regulators were analysed by real time quantitative polymerase chain reaction (RT‐qPCR).Results: We obtained a unique set of paired AT, liver and muscle biopsies and serum samples from 13 people taken at the time of surgery of which 11 returned for a follow‐up SCAT biopsy. While ANGPTL4 expression in muscle was negligible, SCAT ANGPTL4 was highly correlated with OMAT (r = 0.76, p = 0.006) and liver ANGPTL4 (r = 0.67, p = 0.03). Similarly, OMAT ANGPTL4 was also associated with liver ANGPTL4 (r = 0.82, p = 0.004). ANGPTL4 gene expression correlated with hypoxia‐inducible factor (HIF)‐1α. Following bariatric surgery, SCAT HIF‐1α decreased 1.8‐fold and ANGPTL4 1.6‐fold.Conclusions: ANGPTL4 tissue expression shows a close interlink between fat tissue and the liver. Our data suggest an inter‐organ crosstalk of adipose tissue in the pathogenesis of NAFLD which may be exacerbated by HIF‐1α, found at increased levels in dysfunctional obese adipose tissue as result of hypoxia.P108The effect of bariatric surgery on liver outcomes in obese patients with non‐alcoholic fatty liver disease: A systematic reviewHL WALKER1, P Wainwright2,31Faculty Of Medicine, The University of Southampton, Southampton, UK, 2Chemical Pathology and Metabolic Medicine, University Hospital Southampton, Southampton, UK, 3Clinical Biochemistry, University Hospital Southampton, Southampton, UKBackground: Non‐alcoholic fatty liver disease (NAFLD) is rapidly becoming the leading cause of liver‐related morbidity and mortality in the developed world. Obesity and Type 2 diabetes are significant risk factors for its development and progression with the prevalence of NAFLD among these patients estimated to be 80% to 90% and 30% to 50%, respectively. Treatment options are currently limited. Evidence suggests bariatric surgery could halt and potentially reverse the progression of NAFLD; however, current literature presents conflicting data.Aims: To explore the histological, biochemical and clinical outcomes of bariatric surgery in obese patients with NAFLD.Methods: An electronic literature search was carried out gathering papers with data of pre‐ and post‐surgery liver biopsy considering histological features (steatosis, hepatic ballooning, fibrosis and lobular inflammation), biochemical markers (alanine aminotransferase [ALT], aspartate aminotransferase [AST], ALP and gamma glutamyltransferase (GGT)) and clinical outcomes.Results: Twenty‐five studies were selected for final data extraction. ALT and GGT were reported to consistently decrease in all studies, while AST showed very little change during follow‐up. ALP results were varied with two studies reporting an increase. Histological assessments were also positive. Of 25 papers, 24 reported improvements in steatosis, hepatocyte ballooning, fibrosis and lobular inflammation. Unfortunately, there were no clinical outcomes to report on.Conclusion: Bariatric surgery appears to be associated with a marked improvement in both histological and biochemical liver markers of NAFLD. There is a great need for research considering the clinical outcomes of bariatric surgery in NAFLD because it remains unclear if the observed improvements in histology and biochemistry translate into improved clinical outcomes. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Diabetic Medicine Wiley

Basic and clinical science posters: Lipids and fatty liver

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Wiley Subscription Services, Inc., A Wiley Company
Copyright
Diabetic Medicine © 2018 Diabetes UK
ISSN
0742-3071
eISSN
1464-5491
D.O.I.
10.1111/dme.16_13571
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Abstract

P106 Diabetes Remission Clinical Trial (DiRECT): Does hepatic very low density lipoprotein (VLDL) production determine intrapancreatic fat in Type 2 diabetes?A AL‐MRABEH1, SV Zhyzhneuskaya1, C Peters1, AC Barnes2, B Aribisala3, KG Hollingsworth1, H Pilkington4, MEJ Lean5, R Taylor11Magnetic Resonance Centre, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK, 2Human Nutrition Research Centre, Institute of Health and Society, Newcastle University, Newcastle upon Tyne, UK, 3Computer Science Department, Faculty of Science, Lagos State University, Lagos, Nigeria, 4Clinical Ageing Research Unit, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, UK, 5School of Medicine, Dentistry and Nursing, Royal Infirmary, University of Glasgow, Glasgow, UKRefer to Oral number A77P107The adipokine and hepatokine ANGPTL4 is linked to the pathogenesis of fatty liver disease in obesityL McCulloch1, B Knight2, K KOS11Diabetes and Obesity Research Group, University of Exeter, Exeter, UK, 2Exeter National Institute for Health Research (NIHR) Clinical Research Facility, Royal Devon and Exeter NHS Foundation Trust, Exeter, UKAims: Non‐alcoholic liver disease (NAFLD) is a result of ectopic fat distribution which is frequently found in bariatric patients. Rodent studies suggest that the angiopoietin‐like 4 protein ANGPLT4 which is secreted by adipose tissue and the liver promotes lipolysis and may improve hepatic insulin resistance. We postulate that ANGPLT4 plays a role in the adipose‐liver crosstalk linking adipose tissue dysfunction with NAFLD.Methods: Men and women undergoing elective bariatric surgery were recruited to have biopsies of the right and left liver lobe, omental (OMAT) and abdominal subcutaneous tissue (SCAT) and muscle during surgery. A repeated SCAT biopsy was obtained at nine‐month follow‐up. NASH score was defined by histological examination. Transcriptomic signatures of ECM regulators were analysed by real time quantitative polymerase chain reaction (RT‐qPCR).Results: We obtained a unique set of paired AT, liver and muscle biopsies and serum samples from 13 people taken at the time of surgery of which 11 returned for a follow‐up SCAT biopsy. While ANGPTL4 expression in muscle was negligible, SCAT ANGPTL4 was highly correlated with OMAT (r = 0.76, p = 0.006) and liver ANGPTL4 (r = 0.67, p = 0.03). Similarly, OMAT ANGPTL4 was also associated with liver ANGPTL4 (r = 0.82, p = 0.004). ANGPTL4 gene expression correlated with hypoxia‐inducible factor (HIF)‐1α. Following bariatric surgery, SCAT HIF‐1α decreased 1.8‐fold and ANGPTL4 1.6‐fold.Conclusions: ANGPTL4 tissue expression shows a close interlink between fat tissue and the liver. Our data suggest an inter‐organ crosstalk of adipose tissue in the pathogenesis of NAFLD which may be exacerbated by HIF‐1α, found at increased levels in dysfunctional obese adipose tissue as result of hypoxia.P108The effect of bariatric surgery on liver outcomes in obese patients with non‐alcoholic fatty liver disease: A systematic reviewHL WALKER1, P Wainwright2,31Faculty Of Medicine, The University of Southampton, Southampton, UK, 2Chemical Pathology and Metabolic Medicine, University Hospital Southampton, Southampton, UK, 3Clinical Biochemistry, University Hospital Southampton, Southampton, UKBackground: Non‐alcoholic fatty liver disease (NAFLD) is rapidly becoming the leading cause of liver‐related morbidity and mortality in the developed world. Obesity and Type 2 diabetes are significant risk factors for its development and progression with the prevalence of NAFLD among these patients estimated to be 80% to 90% and 30% to 50%, respectively. Treatment options are currently limited. Evidence suggests bariatric surgery could halt and potentially reverse the progression of NAFLD; however, current literature presents conflicting data.Aims: To explore the histological, biochemical and clinical outcomes of bariatric surgery in obese patients with NAFLD.Methods: An electronic literature search was carried out gathering papers with data of pre‐ and post‐surgery liver biopsy considering histological features (steatosis, hepatic ballooning, fibrosis and lobular inflammation), biochemical markers (alanine aminotransferase [ALT], aspartate aminotransferase [AST], ALP and gamma glutamyltransferase (GGT)) and clinical outcomes.Results: Twenty‐five studies were selected for final data extraction. ALT and GGT were reported to consistently decrease in all studies, while AST showed very little change during follow‐up. ALP results were varied with two studies reporting an increase. Histological assessments were also positive. Of 25 papers, 24 reported improvements in steatosis, hepatocyte ballooning, fibrosis and lobular inflammation. Unfortunately, there were no clinical outcomes to report on.Conclusion: Bariatric surgery appears to be associated with a marked improvement in both histological and biochemical liver markers of NAFLD. There is a great need for research considering the clinical outcomes of bariatric surgery in NAFLD because it remains unclear if the observed improvements in histology and biochemistry translate into improved clinical outcomes.

Journal

Diabetic MedicineWiley

Published: Jan 1, 2018

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