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Obesity, gout and the sluggish immune system

21 May 2014

Obesity, gout and the sluggish immune system

Obesity is recognised as a risk factor for gout, cardiovascular disease, type 2 diabetes and some forms of cancer. What is less well known is that carrying excess weight can also prevent the immune system from functioning correctly. For those prone to gout, this could work in their favour!

The prevalence of obesity is increasing worldwide. In New Zealand almost one in three adults and one in nine children are considered obese. The rates are even higher in Maori (48 percent obese) and Pacific (68 percent obese) adults.

Obesity’s effects on the immune system are thought to underlie some of its connections to chronic diseases. The link seems to be the fat tissue itself. Fat cells have been shown to secrete many factors that local immune cells respond to. This promotes a state of overstimulation of the immune system (chronic inflammation), which impairs normal immune function.

For the past decade Malaghan Institute Arthritis and Inflammation Group Leader Dr Jacquie Harper has been investigating the immune responses that drive gout—a disease that is strongly linked with obesity.

“When foods such as liver, kidneys and sardines are broken down by the body, uric acid is released,” says Dr Harper. “Uric acid has many important health benefits and the body is equipped to deal with it, but only up to a certain point.

“A gout attack is triggered by uric acid crystallising in the joints. The immune system perceives the crystals as a threat and launches an immune response against them. It is the resulting inflammation that causes swelling, reddening of the skin and debilitating pain.”

Uric acid levels are higher in obese individuals, increasing their likelihood that they will develop gout. What has been unclear up until now however, is whether their gout attacks are worse than those in non-obese individuals, because of their existing low level of inflammation. Dr Harper’s research, published recently in Rheumatologywould suggest not.

“In collaboration with Auckland Rheumatologist Associate Professor Nicola Dalbeth and colleagues, we investigated the effect of diet-driven obesity on immune cell activity in a model of gout,” says Dr Harper. “Our study is novel in that we focused specifically on immune cells not associated with fat tissue, to determine the wider implications of obesity on immune function.

“We found that obesity elevates the background inflammatory activity of these immune cells, just as it does with fat-associated immune cells. Interestingly however, rather than making things worse, the presence of the crystals actually decreased background inflammation.”

This is good news for obese individuals prone to gout because it suggests that their gout is no worse than that which occurs in some lean individuals. The bad news however is this study further supports the growing evidence that obesity impairs immune function.

While this work has focused on gout, further research is necessary to determine the broader impact of weight gain and dietary fat on the ability of the immune system to respond to different challenges.

This work was funded by the Wellington Medical Research Foundation and the Auckland Medical Research Foundation.

Publication details:
Shaw OM, Pool B, Dalbeth N, Harper JL The effect of diet-induced obesity on the inflammatory phenotype of non-adipose-resident macrophages in an in vivo model of gout. Rheumatology (Oxford) 2014 May 15 (in press)

About the Malaghan Institute of Medical Research
The Malaghan Institute is New Zealand’s leading medical research institute and is based at Victoria University of Wellington’s Kelburn campus. The Institute operates independently and is a charitable trust. Researchers at the Malaghan Institute are focused on developing innovative ways to harness the strength and potency of the immune system, the body’s own natural defence against disease, to treat cancer, asthma and allergy, arthritis and multiple sclerosis.

www.malaghan.org.nz

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