Inflammation is a better indicator of health than BMI in obesity

The level of low-grade, chronic inflammation in the body is a better indicator of metabolic health than simply measuring body mass index, or BMI. 

That’s the contention of (opens in a new window)Dr Fiona McGillicuddy, whose research is focused on unravelling the links between obesity, inflammation and metabolic health. 

“People are pushing back against BMI as a metric of health,” said Dr McGillicuddy. “It’s a tool, but it’s not indicative of how healthy you are. My group is interested in this concept of metabolically healthy versus unhealthy obesity and that the two might be differentiated by how inflamed you are.” 

Dr McGillicuddy is interested in the subacute inflammatory state that exists in lots of different people. “Whether it’s arthritis or psoriasis, nearly every condition characterised by chronic low-grade inflammation is associated with increased cardiovascular risk. We are really interested in the mechanisms of that.” 

Her career began with a degree in pharmacology from UCD. She then moved to the University of Pennsylvania where she investigated lipoproteins – the soluble proteins that transport fat around in the blood plasma – and became particularly interested in how inflammation impacts cardiovascular health. 

That lead on to research into the low-grade inflammation that many of us experience, without realising the health implications. This research, in turn, laid the groundwork for her subsequent investigations into inflammation’s link to obesity and type 2 diabetes, and a return home to Ireland to explore this further. 

Insulin resistance 

Back at UCD, Dr McGillicuddy worked as a senior postdoctoral researcher with Professor Helen Roche on the role of (IL-1) interleukin-1; a small protein known for its potent inflammatory impacts – in driving insulin resistance in obesity. 

Insulin resistance happens when the body’s cells don’t respond properly to the hormone insulin that regulates blood sugars. This means that cells don’t take in glucose from the blood as effectively as they need to, and leads to higher blood sugar levels, and the potential to develop type 2 diabetes. 

“We revealed that by knocking out the IL-1 receptor in mice, we could protect them from high-fat diet-induced insulin resistance,” said Dr McGillicuddy - a finding that got the attention of the scientific community. 

Dr McGillicuddy’s research broadened into a consideration of how dietary fats influence metabolic health. Intriguingly, her research found that, in an obesogenic diet, replacing saturated fats with monounsaturated could lead to healthier outcomes and improved reverse cholesterol trafficking - the process by which cholesterol is removed from cells around the body by high-density lipoprotein (HDL) particles ('good cholesterol') and is brought back to the liver for elimination in the bile and faeces. 

This dramatic, important finding established Dr McGillicuddy’s credentials as a leading researcher investigating the potential for dietary interventions to control chronic inflammation and all of the associated health risks. 

One fascinating avenue of Dr McGillicuddy’s research has looked at why some people with obesity are healthy, by all the standard metabolic measures, while others, who share a similar or even the same BMI, are unhealthy. 

“There is the concept of ‘metabolically healthy obesity,” said Dr McGillicuddy. “My group got really interested in this concept of metabolically healthy versus unhealthy obesity, and that the two might be differentiated by how inflamed you are.” 

Spin out 

Dr McGillicuddy, working with Nova UCD, set up a spin-out company called (opens in a new window)MetHealth, which aims to develop innovative tools for measuring metabolic health in obesity and other diseases by investigating chronic inflammation. 

The company’s technology focuses on analysing the proteins that are associated with HDL particles – the so-called ‘good cholesterol’. This can lead to a more accurate biomarker for assessing metabolic health than ‘traditional’ cholesterol or BMI measurements. 

An accurate biomarker/s that can separate out people living with obesity who are metabolically healthy, from those who are not, and, could enable healthcare providers to focus first on treating the highest-risk patients. “We want to identify the highest risk patients who are most likely to get heart disease, most likely to get cancer, and make sure we are intervening with them,” said Dr McGillicuddy. 

There are potential applications for the technology in several disease areas, other than obesity and type 2 diabetes, she said, notably for metabolic dysfunction associated steatotic liver disease (fatty liver disease), and its more severe form, metabolic dysfunction associated steatohepatitis. 

Given that some 90% of people with obesity have some form of liver fat accumulation, there is a need for a non-invasive diagnostic option to liver biopsies which is associated with risks of post-operative pain, bleeding and infection. “Having a technology that can mirror the liver, but in serum, is one of the biggest unmet needs in the cardiometabolic disease space,” said Dr McGillicuddy. 

Serum is the fluid and solvent component of blood that plays no part in clotting, and it is used in many diagnostic tests as well as blood typing. 

The potential for Dr McGillicuddy’s research to positively impact public health in Ireland and globally is immense. The shift from the traditional measures of obesity to the better methods her work promises, based on a more comprehensive understanding of metabolic health, can save lives. 

Conway Fellow, Dr Fiona McGillicuddy from UCD School of Medicine was in conversation with journalist, Sean Duke