Study Title:

Unfit Fat, Low Adiponectin, Insulin Resistance, and PCOS

Study Abstract

Context: Comprehensive characterization of the adipose tissue in women with polycystic ovary syndrome (PCOS), over a wide range of body mass indices (BMIs), is lacking. Mechanisms behind insulin resistance in PCOS are unclear.

Objective: To characterize the adipose tissue of women with PCOS and controls matched pair-wise for age and BMI, and to identify factors, among adipose tissue characteristics and serum sex steroids, that are associated with insulin sensitivity in PCOS.

Design/Outcome Measures: Seventy-four PCOS women and 31 controls were included. BMI was 18–47 (PCOS) and 19–41 kg/m2 (controls). Anthropometric variables, volumes of subcutaneous/visceral adipose tissue (magnetic resonance imaging; MRI), and insulin sensitivity (clamp) were investigated. Adipose tissue biopsies were obtained to determine adipocyte size, lipoprotein lipase (LPL) activity, and macrophage density. Circulating testosterone, free testosterone, free 17β-estradiol, SHBG, glycerol, adiponectin, and serum amyloid A were measured/calculated.

Results: Comparison of 31 pairs revealed lower insulin sensitivity, hyperandrogenemia, and higher free 17β-estradiol in PCOS. Abdominal adipose tissue volumes/distribution did not differ in the groups, but PCOS women had higher waist-to-hip ratio, enlarged adipocytes, reduced adiponectin, and lower LPL activity. In regression analysis, adipocyte size, adiponectin, and waist circumference were the factors most strongly associated with insulin sensitivity in PCOS (R2=0.681, P < 0.001).

Conclusions: In PCOS, adipose tissue has aberrant morphology/function. Increased waist-to-hip ratio indicates abdominal/visceral fat accumulation, but this is not supported by MRI. Enlarged adipocytes and reduced serum adiponectin, together with a large waistline, rather than androgen excess, may be central factors in the pathogenesis/maintenance of insulin resistance in PCOS.

From press release:

A study from the University of Gothenburg, shows that women with polycystic ovary syndrome (PCOS) have aberrations in their adipose (fat) tissue. This discovery could provide answers as to why these women develop type 2 diabetes more readily, and shows that it is important for their health that women with PCOS do not put on weight.

"We already know that women with PCOS often have insulin resistance, in other words the body's cells are less sensitive to insulin, and are at greater risk of developing type 2 diabetes," says Louise Mannerås-Holm, a researcher at the Department of Physiology at the Sahlgrenska Academy's Institute of Neuroscience and Physiology. "High levels of testosterone in the blood of these women are thought to be one of the main reasons for this." But the current study, published in The Journal of Clinical Endocrinology and Metabolism, shows that aberrations in adipose tissue could be more significant in this respect. Around half of all women with PCOS are overweight or obese and it is widely believed that the excess fat is stored mainly around the middle.

The study therefore pair-matched 31 women with PCOS and 31 women without the syndrome, but of the same age and BMI. Ages ranged from 21 to 37, and BMI from underweight to extremely obese. "The comparison between the groups shows that women with PCOS do not have an abnormally large amount of fat around the middle, but that they do have large fat cells and altered adipose tissue function," says Mannerås-Holm.

In women with PCOS, adipose tissue produces less of the "good" hormone adiponectin which increases the body's sensitivity to insulin. Furthermore, activity of the enzyme lipoprotein lipase is low, which can affect the metabolism of fat in the body.

A total of 74 women with PCOS took part in the study, which also shows that the aberrations in adipose tissue in PCOS could play a key role in increasing these women's risk of developing type 2 diabetes. The factors linked most strongly with insulin resistance were the size of the fat cells, the quantity of adiponectin in the blood and waist size. However, testosterone levels did not play a significant role in this analysis.

"We don't entirely understand the mechanism behind the large fat cells' unfavourable effects, but the results show that it is particularly important for the health of women with PCOS that they don't put on weight," says Mannerås-Holm.

Polycystic Ovary Syndrome (PCOS)

PCOS is the most common hormonal disorder in women of fertile age. Characterised by insulin resistance and high levels of testosterone, PCOS affects 5-10% of fertile women.

The most common symptoms are irregular or disrupted menstruation, problem hair growth, acne and excess weight. In the long term women with PCOS are at greater risk of developing type 2 diabetes, and probably cardiovascular disease too. Extensive research is under way to increase our knowledge of the underlying factors.

Docent Malin Lönn at the Sahlgrenska Academy supervised the study of adipose tissue in PCOS, which was part of an extensive investigation into these women's physical and mental health led by docent Elisabet Stener-Victorin at the Sahlgrenska Academy.

Study Information

L. Manneras-Holm, H. Leonhardt, J. Kullberg, E. Jennische, A. Oden, G. Holm, M. Hellstrom, L. Lonn, G. Olivecrona, E. Stener-Victorin, M. Lonn.
Adipose Tissue Has Aberrant Morphology and Function in PCOS: Enlarged Adipocytes and Low Serum Adiponectin, But Not Circulating Sex Steroids, Are Strongly Associated with Insulin Resistance.
Journal of Clinical Endocrinology & Metabolism
2011 March
Department of Physiology at the Sahlgrenska Academy's Institute of Neuroscience and Physiology,University of Gothenburg, Gothenburg, Sweden.

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