Featured Reagent – Adiponectin
Featured Reagent – Adiponectin
Physiological Significance
Adiponectin (ADPN) (adipocyte complement-related protein of 30kDa (Acrp30)) is an adipokine (protein hormone) produced and secreted by the adipose tissue, an endocrine organ 1. ADPN acts as a messenger in the communication of adipose tissue and metabolic organs. In doing so, ADPN suppresses the production of glucose in the liver through inhibiting the genes involved in glucose production and enhances fatty acid oxidation in skeletal muscle 2.
Consequently, ADPN is a strong protector against several pathological events in various cells through inhibiting inflammation, suppressing cell death and enhancing cell survival 2.
ADPN has been identified as having pleiotropic functions widely associated with anti-atherogenic, anti-diabetic, cardioprotective and anti-inflammatory effects. ADPN levels inversely correlate with insulin levels, BMI, triglyceride levels, insulin resistance (IR), glucose, and most importantly, visceral fat accumulation 3. Moreover, physiological functions of adiponectin have also been observed in inflammation and cardiovascular disease (CVD), especially in atherosclerosis 2.
Fig. 1. Proposed salutary effects of adiponectin 1
Adiponectin Testing
Latex Enhanced Immunoturbidimetric Method
The automated latex enhanced immunoturbidimetric method produces results in as little as ten minutes, facilitating faster patient diagnosis and treatment plan implementation compared to traditional ELISA based testing.
Exceptional correlation
A correlation coefficient of r=0.989 was displayed when compared to commercially available methods.
Extensive measuring range
The healthy range for adiponectin is 2 – 22μg/ml. The Randox adiponectin assay can comfortably detect levels outside of the healthy range, measuring between 0.32 – 23.8μg/ml.
Liquid ready-to-use assay
The Randox adiponectin assay is available in a liquid ready-to-use format for convenience and ease-of-use.
Stability
The Randox adiponectin assay is stable to expiry date when stored at +2 to +8°C and has an onboard stability of 28 days when stored at +10oC.
Applications are available
Applications are available detailing instrument-specific settings for the convenient use of the Randox adiponectin assay on a variety of clinical chemistry analysers. Contact us to enquire about your specific analyser.
APDN has an inverse correlation with abdominal visceral fat (AVF). Low levels of ADPN increases the risk of metabolic abnormalities. Furthermore, excess adipose tissue, especially visceral adipose tissue (VAT) is an important risk factor for IR, correlating with an increased risk of CVD 5.
The most commonly utilised methods for the assessment of AVF are waist circumference and BMI. Waist circumference does not measure total AVF reliably as the visceral fat / subcutaneous fat ratios vary by gender and ethnicity 6 and BMI cannot distinguish between muscle and fat and so classes those with high muscle and low fat mass as being overweight. Moreover, BMI also cannot distinguish between visceral fat and fat that sits beneath the skin 7.
Adiponectin levels are inversely correlated with AVF, proving to be a reliable indicator of at-risk patients.
The traditional biomarkers utilised in the assessment of T2DM risk include: oral glucose tolerance test (OGTT), fasting plasma glucose (FPG) and HbA1c. However, each of these tests are inadequate and a superior biomarker for T2DM risk assessment is vital.
1. JAMA (2009): Adiponectin levels and risk of type 2 diabetes: A systematic review and meta-analysis 8
Higher ADPN levels are associated with a lower risk of T2DM across diverse populations and is currently the strongest and most consistent biomarker of T2DM risk assessment.
2. BMJ Open Diabetes Research & Care (2016): Adiponectin levels predict prediabetes risk: The pathobiology in a biracial cohort (POP-ABC) study 9
Baseline ADPN levels were inversely related to the risk of pre-diabetes among the healthy African Americans and European Americans with a parental history of T2DM enrolled on the POP-ABC study. Despite gender and ethnic difference, this predictive relationship was evident.
The most commonly observed component of metabolic syndrome (MetS) is abdominal obesity. MetS encompasses several conditions
including: hypercholesterolemia, triglyceridemia, glycaemia, hypertension, abdominal obesity and dyslipidaemia. The prevalence of MetS is 31% and is associated with a 1.5-fold increased risk of all-cause mortality, a 2-fold increased risk of coronary heart disease (CHD) and cerebrovascular accident (CVA), and a 5-fold increased risk of T2DM 10, 11, 12.
Adiponectin has been identified as a glucose regulator and lipid homeostasis through its insulin sensitising properties which are associated with MetS.
1. Nutrition and Diabetes (2011): Serum adiponectin level is not only decreased in metabolic syndrome but also in borderline metabolic abnormalities 13
Decreasing ADPN levels begins at an early stage before the onset of hypertension, diabetes, MetS or dyslipidaemia. Moreover, in those with metabolic abnormalities / physiological abnormalities, adiponectin is an important biomarker for the risk assessment of atherosclerosis, both independently and as a reflection of the accumulation of AVF.
2. Cardiovascular Diabetology (2015): Role of adiponectin and free fatty acids on the association between abdominal visceral fat and insulin resistance 14
Subjects with high AVF or low ADPN had a 3-fold increased risk of IR. The combination of low ADPN with high AVF doubled this probability.
It has been recognised that mRNA expression of the ADPN gene and the section of high molecular weight (HMW) oligomeric ADPN are impaired in adipose tissue of obese patients. Epidemiological studies undertaken in different ethnic groups established that low ADPN levels, especially in HMW oligomer, is an independent risk factor for CVD 15. Fig. 2 illustrates the pleiotropic role of adiponectin in the cardiovascular system.
1. PLOS ONE (2013): Adiponectin provides additional information to conventional cardiovascular risk factors for assessing the risk of atherosclerosis in both genders 16
The risk of carotid intima media thickness (CIMT) inversely correlates with ADPN levels in both genders. Adiponectin testing is a significant marker of atherosclerosis and can provide additional information in the assessment of atherosclerotic risk in both genders, independent of conventional cardiovascular risk factors.
2. European Journal of Preventive Cardiology (2015): Adiponectin, type 2 diabetes and cardiovascular risk 17
Increasing ADPN levels in plasma is associated with a decreased risk of T2DM and subsequently, a reduced risk of CVD.
Fig. 2. The pleiotropic role of adiponectin in the cardiovascular system 15
Excess body fat is not only associated with T2DM and CVD, but also with various types of malignancies. Many cancer cell lines express ADPN receptors, and adiponectin in vitro limits cell proliferation and induces apoptosis. Evidence exists supporting adiponectin as a novel risk marker in the diagnosis and prognosis of cancer 17. Fig. 3 illustrates the association between obesity, low levels of adiponectin and cancer progression.
1. Medicine (2018): Serum adiponectin in breast cancer: A meta – analysis 19
The meta-analysis indicates an intriguing association between low levels of ADPN and an increased risk of breast cancer (BC). Furthermore, APDN has the potential to serve as a biomarker of BC risk and aid in the identification of those at a high risk of developing BC.
Fig. 3. The association between obesity, low adiponectin levels and cancer progression 18
2. International Brazilian Journal of Urology (2019): Role of adiponectin in prostate cancer 20
Oxidative stress has been identified as a key event in the initiation, development and progression of PC. ADPN increased cellular anti-oxidative defence mechanisms and inhibited oxidative stress through increasing the NADPH oxidase NOX2 and NOX4 expressions in human 22Rv1 and DU – 145 PC cell lines. The review support ADPN as a protective and safe factor to prevent the progression of PC.
Obesity: The Risk Factor
Obesity, a major global health epidemic that burdens on healthcare systems, has increased at an alarming rate with 39% of adults (18+) classed as overweight and 13% classed as obese in 2016. Moreover, in the same year, 340 million children aged between 5 and 16 were identified as overweight or obese and 41 million children under 5 years of age were also classed as overweight or obese. Worldwide, obesity prevalence rates have almost tripled between 1975 and 2016 21, 22.
The main reason obesity is a massive health problem is because of the secondary diseases that develop due to obesity. Obesity has contributed to 23% of ischaemic heart disease cases, 7 – 41% of specific cancer cases and 44% of diabetes cases. Obesity is now no longer confined to developed countries. As the industrialisation of developing countries continues to emerge, high calorie diets and subsequently obesity increases 23.
Obesity reduces the number of disease free years. It was uncovered that those who were mildly obese lost 3 – 4 more disease – free years and those who were severely obese lost 7-8 more disease free years than non-obese individuals. Consequently, at least 2.8 million deaths per year are attributed to obesity 24, 25.
Obesity is a major risk factor for T2DM, IR, CVD and various types of malignancies. These secondary health-related problems cost the economy “$2 trillion annually and roughly 2.8% of the global gross domestic product (GDP)”. Moreover, childhood obesity costs the economy $14.1 billion annually 26, 27, 23. Whilst there are numerous parties involved to aid in the prevention of obesity, urgent actions are required to prevent obesity and the subsequent secondary health – related problems.
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We Are Randox | Christopher McNally climbs the career leader from Placement to PhD
The name Christopher McNally may be one that you already recognise. In 2016 he earned 1st place in the Science category of the Randox Pinnacle Placement Awards, having caught the attention of Senior Management for his pioneering work developing a new diagnostic for pancreatic cancer.
Fast-forward two years and Christopher is now back at Randox as a PhD student, conducting research in prostate cancer as part of the recently-announced Randox-Ulster University PhD Academy.
We sat down with Chris to hear all about his revolutionary prostate cancer project, what motivated him to sign up to our PhD Academy and what it’s like to be back in the place where his scientific career began.
Here’s Chris’ story.
I came into Randox when I was just 19 years old for my third year at university as part of the company’s year-long placement programme. It was a great way to truly experience a working laboratory outside of the classroom and really cemented my desire to work in biomedical science.
I was lucky enough to be placed in the company’s Donegal branch, Randox Teoranta, which is close to where I grew up in Gartan, and offered me the opportunity to carry out ground-breaking medical research surrounded by my home of Donegal.
I would highly recommend the opportunity to perform an industrial placement to anyone. It helps you to prepare for what comes after university, develops your skills in the area in which you are interested, and refines your laboratory techniques. I was delighted to hear I won in the Science Category of the Randox Pinnacle Placement Awards during my time there as well, and this really inspired a confidence in me that I had become a talented scientist even before I graduated.
When I completed my fourth year of studies at Ulster University, I graduated with a degree in Biomedical Science and Professional Practice, and returned to work for Randox. The traits and qualities I learned during my placement had subsequently brought me to post-graduate employment, and I was thrilled. I was lucky enough to be able to walk straight back into the lab knowing exactly what to do and how to do it.
Despite becoming employed within Randox straight out of university however, I had this feeling that I was not finished with regards to academic study. I knew I wanted to do more, to perform more research. So, when I heard about the Randox-Ulster University PhD Academy I really was intrigued. It was the perfect platform to further my studies and be able to give more to the scientific community.
When choosing the area of research for my PhD I was keen to hear more about a collaborative prostate cancer project led by two of Northern Ireland’s leading cancer researchers Dr Mark Ruddock (Randox) and Dr Declan McKenna (Ulster University). From my time at university and my time spent at Randox, I thought I could bring my experience and knowledge in cancer research into this project, so I thought, let’s go for it.
Ultimately, the project involves looking at prostate cancer patients as well as patients who have other non-serious prostate conditions, and recognising any potential differences in the two. We can then develop a clinical diagnostic test that can identify the men at the highest risk of prostate cancer and stratify the patients accordingly.
The earlier we can do this, the quicker a patient can be treated, or not treated as the case may be. Overdiagnosis is a significant problem in prostate cancer care and many men, who do not have prostate cancer, but present with prostate cancer-like symptoms, unfortunately go through invasive, uncomfortable and most importantly, unnecessary procedures.
This work therefore has real potential to improve the management of prostate cancer, which is currently the most common cancer in males within the UK. It’s a very rewarding field to be working in and I thoroughly enjoy the work I’m doing knowing that it will have a real-life impact on many men. I’m very proud to be able to say that my PhD research will really make a difference and I now know for certain that I will continue working in cancer research after my project is complete.
Knowing that I’m helping to improve the quality of patient’s lives brings a great deal of satisfaction that few jobs can replicate and I’m excited to see what the next three years will bring.
We’re very proud of Christopher and the amazing work he is doing in prostate cancer research, and are delighted that he has made the decision to join the Randox-Ulster University PhD Academy.
For more We Are Randox stories about our amazing colleagues, make sure to follow us on Facebook, Instagram and Twitter and follow the hashtag #WeAreRandox.
For current vacancies in our team, visit careers.randox.com
To find out more about the Randox-Ulster University PhD Academy, please email randoxpr@randox.com
