The effects of obesity on skeletal muscle.
Research type
Research Study
Full title
The effects of abdominal obesity on skeletal muscle structure and function\nSub-study: microRNAs in Obesity\n
IRAS ID
274189
Contact name
Lisa Dowling
Contact email
Sponsor organisation
Sheffield Teaching Hospitals NHS Foundation Trust
Duration of Study in the UK
2 years, 2 months, 30 days
Research summary
Summary of Research
The combination of greater amounts of central fat (abdominal obesity) and low muscle strength, “Dynapenic Abdominal Obesity” (DAO), is associated with a falls risk greater than either condition individually. Falls are concerning due to high economic, social and personal costs. \n\nFew studies have described the characteristics of muscle or how it functions in older adults with DAO. This information will help in understanding the relationship between DAO and falls risk. MicroRNAs are like messengers at the cellular level which promote or obstruct many processes including muscle growth and repair. MicroRNAs are an important developing field which can provide insight into how a disease may be treated. MicroRNAs have already been explored in conditions such as cancer and osteoporosis, however, the role of miRNAs in obesity and muscle has not yet been explored. It is not known whether being obese can change microRNA levels in muscle and how this relates to muscle strength and size. \n\nWe will recruit 4-groups of older women in Sheffield and Liverpool: normal weight with/ without dynapenia and obese with/without dynapenia. Participants will attend 2 visits within 28-days. At Royal Hallamshire Hospital or Liverpool Magnetic Resonance Imaging (MRI) Centre, leg muscle size and fat content will be measured using MRI and whole-body and regional muscle mass measured by DXA. Muscle strength, fatigue and balance will be measured at University of Liverpool or Biomedical Research Centre at Royal Hallamshire Hospital. In Clinical Research Facilities at Northern General Hospital or Aintree University Hospital, a trained clinician will take small biopsies of a thigh muscle (vastus lateralis) to measure the microRNA levels.\n\nThis will allow us to understand how abdominal obesity affects muscle strength, fatiguability, size and microRNAs. By understanding how abdominal obesity acts through these mechanisms we can develop better healthcare advice and identify new treatments.Summary of Results
Older adults have the highest risk of falls. People with low muscle strength or central obesity have a greater risk of falls and fractures at certain sites (e.g. ankle) than people with normal weight or normal muscle strength. It is thought that there is a combined risk of falls and fractures in older adults with both low muscle strength (dynapenia) and central obesity (DAO). However, there are few treatment options available for people with DAO. A better understanding of how DAO develops in people and how people with DAO fall can help us to identify new treatment opportunities. MicroRNAs are found in blood, muscle and fat tissue and levels change with ageing; it is thought that microRNAs may block muscle growth and repair, and this could lead to reduced muscle strength with age.We aimed to identify (i) the level of microRNAs in older women with DAO compared to those with normal weight or central (abdominal) obesity only and (ii) potential reasons (e.g. differences in muscle size, strength, and fatigue) for the increased falls risk.
In a large review of the literature we identified 24 miRNAs potentially associated with DAO. However, we could not find any miRNAs which were different in older women with DAO compared to women with normal weight or obesity only. We measured the muscle strength and muscle size of the thigh (quadriceps and hamstrings). We found that for the same amount of muscle, women with central obesity could produce more force (strength) than women with normal weight; however, this benefit was lost in women with DAO. Looking at the hamstrings, from the same amount of muscle, women with central obesity produced a similar amount of force as women with normal weight; however, women with DAO could not produce as much force as either the women with central obesity or normal weight. Together, these findings suggest that women with DAO have worse muscle quality than women with obesity or normal weight.
In summary, we could not identify a distinct panel of microRNAs in women with DAO. However, muscle quality was lower in women with DAO compared to those with obesity as women with DAO could not produce as much force per unit of muscle. Improving the quality of muscle (e.g. reducing muscle fat, improving electrical signalling) might be an opportunity to treat or prevent DAO in older women with DAO. However, more work is required in larger groups and men.
REC name
Yorkshire & The Humber - Leeds West Research Ethics Committee
REC reference
20/YH/0274
Date of REC Opinion
5 Jan 2021
REC opinion
Further Information Favourable Opinion