Personal profile

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.

Fingerprint Fingerprint is based on mining the text of the person's scientific documents to create an index of weighted terms, which defines the key subjects of each individual researcher.

  • 7 Similar Profiles
Adenosine Triphosphate Medicine & Life Sciences
Insulin-Secreting Cells Medicine & Life Sciences
KATP Channels Medicine & Life Sciences
Leptin Medicine & Life Sciences
Neurons Medicine & Life Sciences
Cell Line Medicine & Life Sciences
Insulinoma Medicine & Life Sciences
Potassium Channels Medicine & Life Sciences

Network Recent external collaboration on country level. Dive into details by clicking on the dots.

Research Output 1980 2018

1 Citations

Bace1-dependent amyloid processing regulates hypothalamic leptin sensitivity in obese mice

Meakin, P. J., Jalicy, S. M., Montagut , G., Allsop, D. J. P., Cavellini, D. L., Irvine, S. W., McGinley, C., Liddell, M. K., McNeilly, A. D., Parmionova, K., Liu, Y-R., Bailey, C. S. L., Dale, J. K., Heisler, L. K., McCrimmon, R. J. & Ashford, M. L. J. 8 Jan 2018 In : Scientific Reports. 8, p. 1-16 16 p., 55

Research output: Contribution to journalArticle

Open Access
File
Obese Mice
Leptin
Amyloid
Obesity
Homeostasis
2 Citations
Open Access
File
NF-E2-Related Factor 2
Fructose
Liver Cirrhosis
Fats
Endoplasmic Reticulum Stress

Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1

Mills, E. L. , Ryan, D. G. , Prag, H. A. , Dikovskaya, D. , Menon, D. , Zaslona, Z. , Jedrychowski, M. P. , Costa, A. S. H. , Higgins, M. , Hams, E. , Szpyt, J. , Runtsch, M. C. , King, M. S. , McGouran, J. F. , Fischer, R. , Kessler, B. M. , McGettrick, A. F. , Hughes, M. M. , Carroll, R. G. , Booty, L. M. & 15 others Knatko, E. V., Meakin, P. J., Ashford, M. L. J., Modis, L. K., Brunori, G., Sévin, D. C., Fallon, P. G., Caldwell, S. T., Kunji, E. R. S., Chouchani, E. T., Frezza, C., Dinkova-Kostova, A. T., Hartley, R. C., Murphy, M. P. & O'Neill, L. A. 5 Apr 2018 In : Nature. 556, 7699, p. 113-117 5 p.

Research output: Contribution to journalLetter

Alkylation
Anti-Inflammatory Agents
Interferon Type I
Cysteine
Lipopolysaccharides

The BACE1 product sAPPβ induces ER stress and inflammation and impairs insulin signaling

Botteri, G., Salvadó, L., Gumà, A., Hamilton, D. L., Meakin, P. J., Montagut , G., Ashford, M. L. J., Ceperuelo-Mallafré, V., Fernández-Veledo, . S., Vendrell, . J., Calderón-Dominguez, M., Serra, D., Herrero, L., Pizarro, J., Barroso, E., Palomer, X. & Vázquez-Carrera, M. 9 Mar 2018 In : Metabolism. 85, p. 59-75 17 p.

Research output: Contribution to journalArticle

Endoplasmic Reticulum Stress
Insulin Resistance
Insulin
Palmitates
Inflammation

The beta secretase BACE1 regulates the expression of the insulin receptor in the liver

Meakin, P., Mezzapesa, A., Benabou, E., Haas, M., Bonardo, B., Grino, M., Brunel, J-M., Biddinger, S. B., Desbois-Mouthon, C., Govers, R., Ashford, M. L. J. & Peiretti, F. 3 Apr 2018 In : Nature Communications. 9, p. 1-14 14 p., 1306

Research output: Contribution to journalArticle

Open Access
File
Amyloid Precursor Protein Secretases
insulin
Insulin Receptor
liver
Liver

Activities 2013 2013

  • 1 Participation in conference

Diabetes UK Professional Conference 2013

Ashford, M. (Participant)
13 Mar 201315 Mar 2013

Activity: Participation in conference

Thesis

Investigation of BACE1 as a stress-induced regulator of neuronal metabolism

Author: Findlay, J. A., 2014

Supervisor: Ashford, M. (Supervisor) & Sutherland, C. (Supervisor)

Student thesis: Doctoral ThesisDoctor of Philosophy

File

Investigation of KATP channel function in response to metabolic and pharmacological manipulation, in the hypothalamic GT1-7 cell line

Author: Haythorne, E., 2014

Supervisor: Ashford, M. (Supervisor) & McCrimmon, R. (Supervisor)

Student thesis: Doctoral ThesisDoctor of Philosophy

File

Nrf2 in metabolic related inflammation in the brain

Author: Liddell, M. K., 2015

Supervisor: Ashford, M. (Supervisor)

Student thesis: Doctoral ThesisDoctor of Philosophy

File

Palmitoylation of the Cardiac Sodium-Calcium Exchanger

Author: Reilly, L., 2014

Supervisor: W. (Supervisor) & Ashford, M. (Supervisor)

Student thesis: Doctoral ThesisDoctor of Philosophy

File

The hypothalamic role of BACE1 in energy homeostasis

Author: Jalicy, S. M., 2016

Supervisor: Ashford, M. (Supervisor)

Student thesis: Doctoral ThesisDoctor of Philosophy

File