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Effects of obesity and weight loss on mitochondrial structure and function and implications for colorectal cancer risk

Lookup NU author(s): Dr Stella Breininger, Dr Fiona MalcomsonORCiD, Dr Sonny Afshar, Emeritus Professor Doug Turnbull, Dr Laura Greaves, Professor John Mathers


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© 2019 The Authors. Colorectal cancer (CRC) is the third most common cancer globally. CRC risk is increased by obesity, and by its lifestyle determinants notably physical inactivity and poor nutrition. Obesity results in increased inflammation and oxidative stress which cause genomic damage and contribute to mitochondrial dysregulation and CRC risk. The mitochondrial dysfunction associated with obesity includes abnormal mitochondrial size, morphology and reduced autophagy, mitochondrial biogenesis and expression of key mitochondrial regulators. Although there is strong evidence that increased adiposity increases CRC risk, evidence for the effects of intentional weight loss on CRC risk is much more limited. In model systems, energy depletion leads to enhanced mitochondrial integrity, capacity, function and biogenesis but the effects of obesity and weight loss on mitochondria in the human colon are not known. We are using weight loss following bariatric surgery to investigate the effects of altered adiposity on mitochondrial structure and function in human colonocytes. In summary, there is strong and consistent evidence in model systems and more limited evidence in human subjects that over-feeding and/or obesity result in mitochondrial dysfunction and that weight loss might mitigate or reverse some of these effects.

Publication metadata

Author(s): Breininger SP, Malcomson FC, Afshar S, Turnbull DM, Greaves L, Mathers JC

Publication type: Article

Publication status: Published

Journal: Proceedings of the Nutrition Society

Year: 2019

Volume: 78

Issue: 3

Pages: 426-437

Print publication date: 01/08/2019

Online publication date: 22/03/2019

Acceptance date: 10/07/2018

ISSN (print): 0029-6651

ISSN (electronic): 1475-2719

Publisher: Cambridge University Press


DOI: 10.1017/S0029665119000533


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