Michael Ashford

+44 (0)1382 383095
Professor of Neuroscience

Bio

Research

Chronic obesity is currently at epidemic levels in the UK and many other countries worldwide and is having a major adverse impact on our society. It is estimated that more 25% of the adult population are obese and around two thirds are either overweight or obese.  Worryingly over the last 20 years there has been a ~3 fold increase in the number of children and adolescents who are obese or overweight. This trend is alarming, as chronic obesity is associated with increased risk of cardiovascular and liver disease and some cancers. Most notably however, obesity is a primary driver for induction of peripheral insulin resistance, which when coupled with pancreatic beta cell functional insufficiency, leads to diabetes. Recent work also indicates that the risk of Alzheimer’s disease is higher in patients with diabetes and obesity. Therefore it is clear that our society is on a trajectory that will see significant increases in the proportion of individuals entering or in old age with severe chronic health issues. This places an enormous burden on the NHS and society generally, which is likely to worsen over the next 10-20 years if effective actions are not taken soon.

 

The aim of our work is to understand, at a molecular level, why and how these diseases are linked, in order to find new ways to prevent their long-term harmful consequences. We currently use a number of different systems to study the interactions between the hormones, leptin and insulin, and glucose and fat metabolism. Our current research projects are addressing: (i) how the enzyme beta secretase (BACE1) influences nutrient metabolism and leptin and insulin sensitivity; (ii) the role of the transcription factor, Nrf2, on glucose and lipid metabolism; (iii) how different cellular stresses influence cell metabolism and function; and (iv) how hypothalamic neurons and pancreatic beta cells sense changes in glucose levels.

Publications

Corrigendum to "The BACE1 product sAPPβ induces ER stress and inflammation and impairs insulin signaling" [Metab Clin Exp 85 (2018) 59-75]
4/2019, Metabolism: Clinical and Experimental
Research Output: Contribution To Journal > Article

Calcium Channel CaV2.3 Subunits Regulate Hepatic Glucose Production by Modulating Leptin-Induced Excitation of Arcuate Pro-opiomelanocortin Neurons
9/2018, Cell Reports
Research Output: Contribution To Journal > Article

The BACE1 product sAPPβ induces ER stress and inflammation and impairs insulin signaling
11/2017, Metabolism
Research Output: Contribution To Journal > Article

Small vessels, dementia and chronic diseases : molecular mechanisms and pathophysiology
2/2018, Clinical Science
Research Output: Contribution To Journal > Article

Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1
2/2018, Nature
Research Output: Contribution To Journal > Article

The beta secretase BACE1 regulates the expression of the insulin receptor in the liver
3/2018, Nature Communications
Research Output: Contribution To Journal > Article

Experimental Nonalcoholic Steatohepatitis and Liver Fibrosis Are Ameliorated by Pharmacologic Activation of Nrf2 (NF-E2 p45-Related Factor 2)
11/2017, CMGH: Cellular and Molecular Gastroenterology and Hepatology
Research Output: Contribution To Journal > Article

Bace1-dependent amyloid processing regulates hypothalamic leptin sensitivity in obese mice
6/2017, Scientific Reports
Research Output: Contribution To Journal > Article

High intensity exercise as a dishabituating stimulus restores counterregulatory responses in recurrently hypoglycemic rodents
12/2016, Diabetes
Research Output: Contribution To Journal > Article

AMP-activated protein kinase activator A-769662 increases intracellular calcium and ATP release from astrocytes in an AMPK-independent manner
12/2016, Diabetes, Obesity & Metabolism
Research Output: Contribution To Journal > Article

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Activities

Diabetes UK Professional Conference 2013

Michael L. J. Ashford (Participant)
13 Mar 201315 Mar 2013

Activity: Participating in or organising an event typesParticipation in conference

Activity Type: Attendance

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