In my previous blog post, I tried to suss out visceral fat obesity in the context of metabolic syndrome. Now I want to tackle its connection with hypertension or high blood pressure. We all know what high blood pressure is, but how and why does it happen in people with metabolic syndrome?
One article states that insulin resistance, obesity, inflammation, and nervous system overactivity —work together to raise blood pressure in people with metabolic syndrome. They cause blood vessels to tighten, prevent them from relaxing, and increase the amount of fluid in the blood vessels, leading to hypertension.
Wow. That’s a lot of factors contributing to high blood pressure. I’m not sure how to break it down. I don’t think I’ll go over all of them in detail, but I’ll do my best to understand it all.
Insulin Resistance x Blood Pressure
Here’s what I’ve read about insulin and blood pressure:
- Excess insulin makes the kidneys keep more sodium (salt), which can raise blood pressure.
- Insulin resistance also causes blood vessels to tighten (vasoconstriction) and the nervous system to become overactive, both of which increase blood pressure.
High Insulin → High Blood Pressure
When you develop insulin resistance, excess insulin accumulates in your bloodstream. This heightened level of insulin prompts the kidneys to retain more sodium by directly stimulating the reabsorption of sodium ions within the renal tubule. Insulin attaches to receptors on kidney cells, activating intracellular signaling pathways that stimulate sodium transporters, resulting in an increase in sodium being reabsorbed from urine back into the blood.
Jeebus! What a complex passage. Let me simplify it.
High Insulin → kidney Salt retention → High Blood Pressure
I’ll go back all the way to how insulin first gets into the blood. The system that releases insulin into the blood is only aware of the glucose levels. That system lives in the pancreas and has special cells called beta cells in an area called the “islets of Langerhans.”
Yeah, I know it sounds like some mysterious German archipelago, but it’s not. It’s just named after a german who discovered these cells. I think I’m moving off topic, time to get back on track.
Back to the beta cells – these beta cells act like sensors, constantly “checking” how much glucose is in your blood. For those who are metabolic resistant, beta cells just keep on telling your system to release more insulin, because the body’s tissues are less responsive to it. Hence the term insulin resistant.
kidney Salt retention → high blood volume → High Blood Pressure
The insulin tells the kidneys to grab more salt from the stuff they’re about to turn into pee and put it back in your body. Why? To maintain enough blood volume so that the glucose in the bloodstream can be used as energy by other cells in the body, such as the ones found in your organs and muscles in your body. Low blood volume would significantly impair this delivery. High blood volume means high blood pressure, as more blood is pushing against the vessel walls.
High insulin → endothelial dysfunction
Moving on to the second point: How does insulin resistance can cause blood vessels to tighten? Insulin resistance can cause blood vessels to tighten because it leads to impaired function of the endothelium, the lining of blood vessels. Insulin disrupts the normal signaling pathways that lead to the production of nitric oxide (NO), a crucial vasodilator, resulting in decreased blood vessel relaxation and contributing to endothelial dysfunction.
endothelial dysfunction → Less Nitric Oxide → constricted Blood vessels
In the human body, the endothelial receptors create nitric oxide synthase (eNOS), an enzyme that produces nitric oxide (NO) – both which helps regulate blood pressure and maintain cardiovascular health. Insulin normally binds to its receptor on endothelial cells, activating a pathway for stimulating eNOS activity and NO production. When insulin resistance occurs, the pathway becomes less responsive to insulin, leading to reduced activation of eNOS and consequently decreased NO production. Thus leading to constricted blood vessels and high blood pressure.
Interestingly, medicines that improve insulin resistance (like metformin) or lower blood sugar can also help control blood pressure.
Visceral Fat x Blood Pressure
Did you know visceral fat is more than just stored energy? I didn’t! Here’s what I have found: it acts like an organ, releasing chemicals called adipocytokines – a group of proteins and peptides produced by fat cells that help regulate many bodily functions. These chemicals include substances like:
- Leptin – influences the nervous system and raises blood pressure
- Tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6)- which cause inflammation and high blood pressure, called inflammatory cytokines (signaling proteins). Let’s just call them “Inflammation causing chems’
- Angiotensinogen conversion to angiotensin II – leads to tight blood vessels and high blood pressure.
Isn’t that crazy? I feel like my belly is a bag of chemicals now.
High Leptin → “Fight or flight” → High Blood Pressure
Leptin is a hormone produced by visceral fat and primarily influences the nervous system by activating the sympathetic nervous system. This activation results in heightened blood pressure through processes such as an increased heart rate and vasoconstriction. Essentially, elevated leptin levels—commonly linked to obesity—can lead to higher blood pressure by triggering the body’s “fight or flight” response. Medical journals call this kind of reaction a “sympathetic nervous system overactivity.”
visceral fat cell death → High TNF-alpha and IL-6 → Inflammation → High Blood Pressure
Like any other cells in the body, visceral fat cells can undergo cell death. The more visceral fat, the more the cells go through their life cycle. This process triggers a signaling pathway that activates a sort of cleanup crew. It involves the production of TNF-alpha and IL-6 through a complex mechanism that includes the activation of immune cells, especially macrophages (a type of white blood cell), within the adipose tissue (just another word for visceral fat tissue). These macrophages release these Inflammation causing chems in response to cellular damage. Several research studies indicate that these inflammatory cytokines cause hypertension by restricting vascular flow especially in the kidneys.
Angiotensinogen → Angiotensin II → High Blood Pressure
Visceral fat signals the conversion of angiotensinogen to angiotensin II by expressing high levels of the precursor protein angiotensinogen (AGT) which is needed to convert Angiotensinogen. Angiotensinogen, a protein produced by the liver and is used to help regulate blood pressure. To do that it must be converted into angiotensin II by enzymes in the kidneys and and then another set of enzymes excreted from the lungs. Once angiotensin II is created in the bloodstream, it then binds to receptors on blood vessel walls, causing the smooth muscle cells to contract and narrow the blood vessels (vasoconstriction), which increases blood pressure.
In short, the fat tissue itself acts as a local source of this hormone, promoting its production even when levels are already high.
Summary:
Insulin resistance raises blood pressure by
- Signaling the kidneys to retain salt
- Causing blood vessels to tighten by disrupting endothelial cells functions
- Causing endothelial cells to produce less nitric oxide which is needed to relax blood vessel walls
- Causing “Fight or Flight” hormones to be released
- Triggering “Inflammation causing chems” to be released
Holy-moly! No wonder it’s a grueling struggle to control high blood pressure, especially when there are so many hormones and proteins working toward raising it. What an interesting hike up to the high blood pressure summit. I feel that I really know more about what’s happening in my body. I feel confident I can get my hypertension under control.
I’d like to remind readers that I am not a medical professional, just a person on a journey to understand more about her health. If you would like to know more here are my resources:
Resources:
Caiazzo, Elisabetta, et al. “Circulating Cytokines and Risk of Developing Hypertension: A Systematic Review and Meta-Analysis.” Pharmacological Research, vol. 200, 29 Dec. 2023, p. 107050. Accessed 24 Jan 2025
Cleveland Clinic. “Blood Volume Test | Cleveland Clinic.” Cleveland Clinic, 2019. Accessed 24 Jan 2025
DeFronzo, R.A. “The Effect of Insulin on Renal Sodium Metabolism.” Diabetologia, vol. 21, no. 3, Sept. 1981, Accessed 24 Jan 2025.
Giacchetti, G., et al. “Overexpression of the Renin-Angiotensin System in Human Visceral Adipose Tissue in Normal and Overweight Subjects.” American Journal of Hypertension, vol. 15, no. 5, 1 May 2002, pp. 381–388, Accessed 24 Jan 2025.
Kolb, Hubert. “Obese Visceral Fat Tissue Inflammation: From Protective to Detrimental?” BMC Medicine, vol. 20, no. 1, 27 Dec. 2022, Accessed 24 Jan 2025
Kolka, Cathryn M., and Richard N. Bergman. “The Endothelium in Diabetes: Its Role in Insulin Access and Diabetic Complications.” Reviews in Endocrine and Metabolic Disorders, vol. 14, no. 1, 10 Jan. 2013, pp. 13–19, Accessed 24 Jan 2025
Mehaffey, Eamonn, and Dewan S. A. Majid. “Tumor Necrosis Factor-α, Kidney Function, and Hypertension.” American Journal of Physiology-Renal Physiology, vol. 313, no. 4, 1 Oct. 2017, pp. F1005–F1008. Accessed 24 Jan 2025
Stanciu, Silviu, et al. “Links between Metabolic Syndrome and Hypertension: The Relationship with the Current Antidiabetic Drugs.” Metabolites, vol. 13, no. 1, 5 Jan. 2023, p. 87. Accessed 24 Jan 2025
