Why inflammation in body fat isn't always a bad thing
Inflammation in body fat may not always be harmful, according to new EU-funded research which contrasts with earlier ideas that link inflammation in body fat to insulin resistance, and ultimately to type 2 diabetes. The findings may eventually lead to new treatments for type 2 diabetes. The results of the study, by researchers at the Karolinska Institutet in Sweden, are published in the New England Journal of Medicine (NEJM). EU support for the work came from two projects: HEPADIP ('Hepatic and adipose tissue and liver dysfunction in the metabolic syndrome'), which received EUR 11.7 million under the 'Life sciences, genomics and biotechnology for health' Thematic area of the Sixth Framework Programme (FP6), and ADAPT ('Adipokines as drug targets to combat adverse effects of excess adipose tissue'), which was funded under the Health Theme of the Seventh Framework Programme (FP7) to the tune of EUR 3 million. Previous work by the Karolinska Institutet team demonstrated that adult humans are continually producing new fat cells (adipocytes) to replace dead cells. Furthermore, overweight people generate and replace more adipocytes than lean people. In patients with obesity, fatty tissue is characterised by low grade inflammation and higher levels of inflammatory factors such as tumour necrosis factor alpha (TNF-alpha) and interleukin-6. These proteins are thought to be particularly harmful because they alter the function of adipose tissue and are known to inhibit the action of insulin. However, the researchers wondered if these proteins might actually play a crucial role in normal adipose tissue function. 'Inflammation may be essential for sensing nutritional needs and maintaining homeostasis in adipose tissue,' the scientists write in their paper. In this study, the researchers took samples of adipose tissue from 23 healthy, lean young women with a body mass index (BMI) of between 20 and 25. The team analysed the levels of inflammatory factors in the samples. Their results revealed a strong relationship between the ability of adipose tissue to produce TNF-alpha and the women's BMI as well as the size and number of fat cells. 'The hypothesis has been that inflammation in adipose tissue indirectly causes insulin resistance and thereby type 2 diabetes,' commented the lead author of the paper, Professor Peter Arner of the Karolinska Institutet's Endocrinology Unit. 'However, when we investigated adipose tissue from healthy and lean young women, we found that inflammation also is necessary for fat cell turnover in the lean, healthy state. This observation was only made for TNF-alpha, since there was no relationship between other inflammatory factors and adipocyte size or number.' The team carried out the same test on young obese women with BMIs ranging from 31 to 48 and found no relationship between TNF-alpha levels and BMI, body fat or adipocyte volume. 'Our [...] findings suggest that TNF-alpha in lean premenopausal women has a physiological role in determining the total mass and volume of adipose tissue, perhaps through the regulation of adipogenesis or lipid storage in adipocytes (or both),' the researchers write. 'We cannot say whether this role also occurs in older women or men.' Professor Arner's team now plans to continue their investigations into how TNF-alpha regulates the regeneration and break down of fat cells. Ultimately, they hope their work will result in new treatments for type 2 diabetes effectively bringing relief to those suffering from the world's most common form of diabetes, which represents almost 90% of diabetic cases in Europe.
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Sweden