Adiponectin: the forgotten PCOS hormone

What is it?

Hello everyone,

How is your May going? We are officially in summer territory!!

Today I want to discuss an overlooked hormone - Adiponectin.

I have come across this hormone in almost all my PCOS research, but I have never sat down and wrote an in-depth article about it. It’s most likely because is overlooked in mainstream explanation of PCOS - but here at The PCOS Newsletter we are not mainstream.

Women with PCOS have been found to have lower levels of adiponectin which has a huge impact on our metabolism. This is also true for lean PCOS. Here is why.

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What is Adiponectin?

Adiponectin is both a hormone and a protein. Let me explain. A hormone is a signalling molecule - it goes to specific organs and tells them to do things. A protein is made out of amino acids that have structural, enzymatic, or regulatory functions. It does more than a hormone essentially,

This molecule is released primarily by our adipose tissue - our fat but can also be made by other tissues, including theca cells - the cells in our ovaries that produces androgens. Seeing a connection already?

Due to it being a hormone, it functions through binding to specific receptors, primarily adiponectin receptor 1 (AdipoR1) and adiponectin receptor 2 (AdipoR2).

• AdipoR1 signaling: Primarily activates AMPK, which regulates energy homeostasis. You will hear a lot about AMPK in relation to PCOS.
  When energy levels in cells are low, AMPK activates pathways that produce more energy and slows down processes that consume energy. This ensures that cells can maintain their essential functions, especially during times of stress or increased energy demand.

• AdipoR2 signaling: Primarily activates PPAR-α, which helps the breakdown and use of fats in the body, helping to control blood fat levels, support energy production during fasting, and reduce inflammation.

As you can tell, adiponectin activates some important functions in the body related to energy metabolism and as a result is able to:

1. Enhance insulin sensitivity: It promotes the body's ability to use insulin effectively, helping maintain blood glucose levels in a healthy range.

2. Reduce gluconeogenesis: In the liver, adiponectin decreases glucose production by inhibiting the transcription of key enzymes.

3. Enhance fatty acid oxidation: Through AMPK activation, adiponectin increases fatty acid burning in skeletal muscle and liver, reducing triglyceride accumulation.

4. Improved glucose uptake: It enhances glucose transport into muscle cells through activation of AMPK.

In addition to metabolism, it does more:

1. Anti-inflammatory action: It suppresses inflammation through multiple mechanisms.

2. Antifibrotic properties: it helps prevent excessive tissue scarring in various organ.s

3. Antioxidant effects: It helps neutralise harmful reactive oxygen species.

4. Cell survival promotion: it protects cells from apoptosis (programmed cell death)

5. Cardiovascular protection: It has beneficial effects on the heart and blood vessels, potentially reducing the risk of atherosclerosis.

Overall, an important little guy/girl. Low levels (hypoadiponectinemia) are associated with conditions such as obesity, insulin resistance, metabolic syndrome, T2DM, and CVD. Unfortunately we have low levels….Great!

What happens in women with PCOS?

Multiple studies have shown reduced adiponectin levels in women with PCOS:

• these levels are independent of BMI meaning adiponectin levels are low regardless of weight - which can explain some of the lean PCOS symptoms

• direct correlation with insulin resistance - this is not only in PCOS but all other people with metabolic syndrome

• obese women with PCOS exhibit even lower adiponectin levels compared to normal-weight women with PCOS.

• In addition to the metabolic action, adiponectin in the ovaries has anti-androgenic activity. Adiponectin reduces androstenedione (a key androgen) in theca cells by downregulating genes like CYP17A1 (androgen-producing enzyme) and LH receptors. Theca cells in PCOS ovaries show fewer AdipoR1/AdipoR2 receptors and as a result reduced adiponectin, which of course blunting its anti-androgenic effects.

The genetic link

The reason for this reduced adiponectin in women with PCOS is partially genetic. A meta-analysis found a correlation between adiponectin levels, the ADIPOQ gene and PCOS. The reason for these variations are not clear, some say it’s evolutionary. Interestingly the variations’s association with PCOS risk differs across ethnic groups - they are stronger in Caucasians/East Asians, suggesting population-specific evolutionary drivers, such as adaptations to regional diets or climate.

Weight

For those overweight, enlarged fat cells found tend to secrete less adiponectin. The inflammation created by excess weight also supresses adiponectin prodcution together with down regulating the receptors.

In addition to the metabolic action, adiponectin in the ovaries has anti-androgenic activity. Adiponectin reduces androstenedione (a key androgen) in theca cells by downregulating genes like CYP17A1 (androgen-producing enzyme) and LH receptors. Theca cells in PCOS ovaries show fewer AdipoR1/AdipoR2 receptors and as a result reduced adiponectin, which of course blunting its anti-androgenic effects.

Can I boost adiponectin levels?

Yes, you can.

Weight loss, due to the effect weight has on the hormone, will inevitably boosts adiponectin levels. However, weight loss is a result of certain changes and actions. It’s actually exercise and diet that will get you there.

The Mediterranean diet, together with exercise, low glycemic index foods will lead to better adiponectin levels. In addition, a review of 52 studies showed that the presence of fiber in the diet contributed to an increase in adiponectin of up to 60–115%.

This is why people over complicate health. It’s the foundation of good nutrition and movement that leads to health.

Omega 3 fatty acids have also been shown to increase adiponectin levels together with Vitamin D and Magnesium supplementations.

Can you test adiponectin levels?

Yes, adiponectin levels can be tested with a simple blood test. The adiponectin test measures the concentration of this hormone in your blood, usually after an overnight fast. I have not yet tried this test, but it’s definetely on my list. I am super curious.

Hope you have enjoyed learning about another hormone that influences our health and have one more reason to follow a healthy diet rich in nutrients and movement.

See you next Sunday,

Francesca

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1. Jensterle, M. (2013) ‘Adiponectin and Polycystic Ovary Syndrome’, Biological Research for Nursing, 15(2), pp. 142–150. doi:10.1177/1099800411431674

Liu, Z., Wang, Z., Hao, C., Tian, Y. and Fu, J. (2018) ‘Effects of ADIPOQ polymorphisms on PCOS risk: a meta-analysis’, BMC Medical Genetics, 19, Article 197. doi:10.1186/s12881-018-0702-4.

Corbould, A., Kim, Y.B., Youngren, J.F., Pender, C., Kahn, B.B., Lee, J. and Dunaif, A. (2013) ‘Adiponectin and its receptors in the ovary: further evidence for a link between obesity and hyperandrogenism in polycystic ovary syndrome’, Endocrinology, 154(6), pp. 2308–2318. doi:10.1210/en.2012-2131.6

Jabakhanji, A., Menzel, J., Biemann, R., Mai, K., Abraham, K. and Weikert, C. (2021) ‘The Influence of Nutrition on Adiponectin-A Narrative Review’, Nutrients, 13(5), Article 1442. doi:10.3390/nu13051442.