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Obesity affects about 700 million adults worldwide and its prevalence continues to increase steadily in most countries, including China. The effects of obesity or adiposity (levels of body fat) on metabolic traits such as a blood pressure and blood glucose levels, cardiovascular diseases, type 2 diabetes, and some cancers are well known and are well-publicised targets for public health initiatives. However, more research is needed to understand the mechanisms behind how obesity and adiposity cause diseases so that more targeted interventions can be developed.

In this study, published in the European Journal of Epidemiology, researchers from Oxford Population Health and Peking University analysed observational and genetic data from 3,977 adults who participated in the China Kadoorie Biobank (CKB) study. The study participants had no prior history of cardiovascular disease and their average BMI was 23.9 kg/m2, with only 6% of participants being obese, defined as having a BMI of more than 30 kg/m2.

The researchers looked at 1,463 proteins contained within the study participants’ blood samples to identify which proteins were associated with BMI and to understand how they might cause disease, using conventional, genetic and multiple other approaches. They also used novel genetic methods to explore whether or not some proteins can affect BMI, which may inform future drug development for the treatment of obesity.  The majority of drugs available that have been designed to target obesity and adiposity work by altering the way that proteins in our bodies behave.

Key findings:

  • While the study population had a relatively lean average BMI, analysis showed that BMI was significantly associated with over 1,000 proteins;
  • Analysis of genetic data provided evidence that BMI may cause changes to the blood levels of more than 300 proteins, with the proteins showing the strongest casual relationships being leptin, FABP4, GOLM2, PON3, and NCAN;
  • Further analysis showed that adiposity influenced multiple proteins that are involved in biological functions related to atherosclerosis (thickening or hardening of arteries), lipid metabolism (how the body processes fats for energy), tumour progression, inflammation, and immune function that might increase future disease risk;
  • In addition, the study has provided genetic evidence that eight proteins may also influence a person’s BMI. Among them, two were found to have an important function in adipose tissue (OGN) and in the liver (ITIH3), which could be prioritised as potential drug targets for treating obesity and obesity-related disease;
  • Similar analysis of the participants in the UK Biobank study, as part of replications showed a strong similarity in the relationships between proteins and adiposity when compared to the Chinese population, despite a broader range of BMIs.

Dr Pang Yao, a lead author of the study and research fellow at Oxford Population Health, said ‘The results of this study provide further evidence for the causal relationship between adiposity and proteins involved in multiple biological process, which adds to other known causes of adiposity such as lipids.’

Dr Andri Iona, a lead author of the study and senior statistician at Oxford Population Health said ‘It was well known that adiposity can affect how proteins behave, but we have been able to demonstrate clearly that the relationship between adiposity and proteins works both ways. This research has identified potential targets for future drug development to prevent obesity and adiposity-related diseases.’

The researchers note that future studies involving larger sample sizes and different genetic instruments are needed to further replicate and clarify the effects of different proteins on BMI and adiposity levels, including how different proteins interact with one another and how shared genetic variants may cause proteins to behave differently in different populations.