UNDERSTANDING MEDIATORS OF METABOLIC DISEASE

Grant number: 1143224 | Funding period: 2018 - 2021

Completed

Abstract

This research proposal will identify changes in liver-secreted proteins during the development of fatty liver, and in the transition from fatty liver to the more advanced form of liver disease, non-alcoholic steatohepatitis (NASH). Understanding the differences in protein secretion between NASH patients and patients with normal/fatty liver will provide the opportunity to identify disease biomarkers that could be determined from a blood sample. This will provide a major shift in clinical care.

Related publications (16)

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Investigating dual inhibition of ACC and CD36 for the treatment of nonalcoholic fatty liver disease in mice.

Camille J Devereux, Jacqueline Bayliss, Stacey N Keenan, Magdalene K Montgomery, Matthew J Watt

2023-02-01

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. Dysregulation in hepatic lipid metabo..

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Proteomic analysis reveals exercise training induced remodelling of hepatokine secretion and uncovers syndecan-4 as a regulator of hepatic lipid metabolism

William De Nardo, Paula M Miotto, Jacqueline Bayliss, Shuai Nie, Stacey N Keenan, Magdalene K Montgomery, Matthew J Watt

2022-04-13

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is linked to impaired lipid metabolism and systemic insulin resistance, which..

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Deep proteomic profiling unveils arylsulfatase A as a non-alcoholic steatohepatitis inducible hepatokine and regulator of glycemic control

Magdalene K Montgomery, Jacqueline Bayliss, Shuai Nie, William De Nardo, Stacey N Keenan, Paula M Miotto, Hamzeh Karimkhanloo, Cheng Huang, Ralf B Schittenhelm, Anthony S Don, Andrew Ryan, Nicholas A Williamson, Geraldine J Ooi, Wendy A Brown, Paul R Burton, Benjamin L Parker, Matthew J Watt

2022-03-10

Non-alcoholic steatohepatitis (NASH) and type 2 diabetes are closely linked, yet the pathophysiological mechanisms underpinning th..

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Hexosaminidase A (HEXA) regulates hepatic sphingolipid and lipoprotein metabolism in mice

Magdalene K Montgomery, Amanuiel Z Taddese, Jacqueline Bayliss, Shuai Nie, Nicholas A Williamson, Matthew J Watt

2021-12-01

Hexosaminidase A (HexA), a heterodimer consisting of HEXA and HEXB, converts the ganglioside sphingolipid GM2 to GM3 by removing a..

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Ectodysplasin A Is Increased in Non-Alcoholic Fatty Liver Disease, But Is Not Associated With Type 2 Diabetes

Jacqueline Bayliss, Geraldine J Ooi, William De Nardo, Yazmin Johari Halim Shah, Magdalene K Montgomery, Catriona McLean, William Kemp, Stuart K Roberts, Wendy A Brown, Paul R Burton, Matthew J Watt

2021-03-04

UNLABELLED: Ectodysplasin A (EDA) was recently identified as a liver-secreted protein that is increased in the liver and plasma of..

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Perilipin 5 S155 phosphorylation by PKA is required for the control of hepatic lipid metabolism and glycemic control

Stacey N Keenan, William De Nardo, Jieqiong Lou, Ralf B Schittenhelm, Magdalene K Montgomery, James G Granneman, Elizabeth Hinde, Matthew J Watt

2021-02-15

Perilipin 5 (PLIN5) is a lipid-droplet-associated protein that coordinates intracellular lipolysis in highly oxidative tissues and..

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Epicardial Adipose Tissue Accumulation Confers Atrial Conduction Abnormality

Chrishan J Nalliah, James R Bell, Antonia JA Raaijmakers, Helen M Waddell, Simon P Wells, Gabriel B Bernasochi, Magdalene K Montgomery, Simon Binny, Troy Watts, Subodh B Joshi, Elaine Lui, Choon Boon Sim, Marco Larobina, Michael O'Keefe, John Goldblatt, Alistair Royse, Geoffrey Lee, Enzo R Porrello, Matthew J Watt, Peter M Kistler

2020-09-08

BACKGROUND: Clinical studies have reported that epicardial adipose tissue (EpAT) accumulation associates with the progression of a..

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SMOC1 is a glucose-responsive hepatokine and therapeutic target for glycemic control

Magdalene K Montgomery, Jacqueline Bayliss, Camille Devereux, Ayenachew Bezawork-Geleta, David Roberts, Cheng Huang, Ralf B Schittenhelm, Andrew Ryan, Scott L Townley, Luke A Selth, Trevor J Biden, Gregory R Steinberg, Dorit Samocha-Bonet, Ruth CR Meex, Matthew J Watt

2020-09-02

Intertissue communication is a fundamental feature of metabolic regulation, and the liver is central to this process. We have iden..

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Molecular regulators of lipid metabolism in the intestine - Underestimated therapeutic targets for obesity?

Mercedes Davalos-Salas, John M Mariadason, Matthew J Watt, Magdalene K Montgomery

2020-08-01

The incidence of obesity and type 2 diabetes continues to rise across the globe necessitating the need to identify new therapeutic..

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Inter-organelle Communication in the Pathogenesis of Mitochondrial Dysfunction and Insulin Resistance

Stacey N Keenan, Matthew J Watt, Magdalene K Montgomery

2020-04-18

PURPOSE OF REVIEW: Impairments in mitochondrial function in patients with insulin resistance and type 2 diabetes have been dispute..

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The role of Ap2a2 in PPAR alpha-mediated regulation of lipolysis in adipose tissue

Magdalene K Montgomery, Jacqueline Bayliss, Stacey Keenan, Sarah Rhost, Stephen B Ting, Matthew J Watt

2019-12-01

Adipose tissue plays a major role in the regulation of systemic metabolic homeostasis, with the AP2 adaptor complex being importan..

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The Liver as an Endocrine Organ-Linking NAFLD and Insulin Resistance

Matthew J Watt, Paula M Miotto, William De Nardo, Magdalene K Montgomery

2019-10-01

The liver is a dynamic organ that plays critical roles in many physiological processes, including the regulation of systemic gluco..

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Mitochondrial Dysfunction and Diabetes: Is Mitochondrial Transfer a Friend or Foe?

Magdalene K Montgomery

2019-06-01

Obesity, insulin resistance and type 2 diabetes are accompanied by a variety of systemic and tissue-specific metabolic defects, in..

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Impact of Lipotoxicity on Tissue "Cross Talk" and Metabolic Regulation

Magdalene K Montgomery, William De Nardo, Matthew J Watt

2019-03-01

Obesity-associated comorbidities include non-alcoholic fatty liver disease, Type 2 diabetes, and cardiovascular disease. These dis..

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Perilipin 5 Deletion in Hepatocytes Remodels Lipid Metabolism and Causes Hepatic Insulin Resistance in Mice

Stacey N Keenan, Ruth C Meex, Jennifer CY Lo, Andrew Ryan, Shuai Nie, Magdalene K Montgomery, Matthew J Watt

2019-03-01

Defects in hepatic lipid metabolism cause nonalcoholic fatty liver disease and insulin resistance, and these pathologies are close..

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Suppressing fatty acid uptake has therapeutic effects in preclinical models of prostate cancer

Matthew J Watt, Ashlee K Clark, Luke A Selth, Vanessa R Haynes, Natalie Lister, Richard Rebello, Laura H Porter, Birunthi Niranjan, Sarah T Whitby, Jennifer Lo, Cheng Huang, Ralf B Schittenhelm, Kimberley E Anderson, Luc Furic, Poornima R Wijayaratne, Maria Matzaris, Magdalene K Montgomery, Melissa Papargiris, Sam Norden, Maria Febbraio

2019-02-06

Metabolism alterations are hallmarks of cancer, but the involvement of lipid metabolism in disease progression is unclear. We inve..

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