A new study by researchers from Oxford Population Health and Peking University has offered new insights into proteins carried in the blood that may influence overall body fat (general adiposity) and fat distribution around the waist (central adiposity) and the underlying biological mechanisms. The study is published in Communications Biology.
Excess weight and obesity affect over 2 billion adults globally and are major health concerns in many countries, including China. Having a higher level of body fat, or adiposity, is a known risk factor for heart disease, type 2 diabetes, cancer, and infections, yet the specific biological mechanisms are not fully understood.
Researchers conducted an extensive proteo-genomic analysis involving genetic data and blood samples collected from 3,977 participants from the China Kadoorie Biobank study. They analysed almost 3,000 different proteins found in blood plasma. The participants, who had no prior history of cardiovascular disease, had an average body mass index (BMI) of 23.9 kg/m², with only 6% classified as obese (BMI >30 kg/m²). By focusing on a lean population, the researchers aimed to uncover biological factors affecting general and central adiposity. The results were then compared to samples collected from participants in the UK Biobank study to see whether these findings also applied to people of European descent.
Key findings:
- In the Chinese population, researchers found over 650 proteins likely to affect levels of general adiposity, where body fat is evenly distributed, and central adiposity, where body fat is focused around the waist. Over 90% of these associations were also identified in the European population;
- 275 of these proteins were uniquely associated with a single indicator of adiposity, such as BMI, body fat percentage, waist circumference, or waist-to-hip ratio;
- 80 proteins were consistently associated with all four of these indicators and were more strongly associated with measures of central adiposity;
- The findings revealed that adiposity affects proteins involved in multiple biological processes, including narrowing of arteries, lipid metabolism, tumour progression, inflammation, and regulation of blood pressure, with certain differences between measures of general and central adiposity;
- The was also genetic evidence that 31 proteins influence BMI and/or waist circumference levels, with ten proteins – most notably ADH1B, ALDH2, and SERPINF2 – showing strong evidence of sharing the same genetic variant with adiposity;
- Furthermore, seven of these proteins (ITIH3, CFB, EFEMP1, TXNDC15, SERPINF2, FN1, and OGN) were replicated in European populations, reinforcing their role in adiposity and highlighting their potential as targets for obesity-related interventions.
Dr Andri Iona, a lead author and senior statistician at Oxford Population Health, commented ‘Our study has clearly demonstrated that general and central adiposity have both unique and shared protein associations, enhancing our understanding of how different fat distributions impact biological processes and identifying potential targets for future drug development to prevent obesity and related diseases.’
Dr Pang Yao, a lead author and senior molecular epidemiologist at Oxford Population Health, added ‘Our findings highlight that central adiposity, particularly waist-to-hip ratio, significantly impacts lipid metabolic pathways, which may explain the increased risk of metabolic diseases linked to abdominal fat distribution.’
The study highlights the complex relationship between adiposity and protein expression, identifying proteins that affect or are affected by general and central adiposity. This opens the door to developing targeted treatments for obesity and its associated health risks. The researchers emphasise the need for further studies with larger and more diverse populations to confirm these findings and translate them into effective therapies.