How Toxic Fat Cells Cause Metabolic Syndrome: The Short Version

Fat cells actively regulate your metabolism

Jump down to How Fat Dysfunction Messes with Your Health

Forget everything you know about fat cells. Fat cells don't just sit around scrolling TikTok while waiting for someone to eat a sugary donut or carb laden Big Mac so they can store the excess calories in the one spot you don't want them to do so. They are active participants in regulating your metabolism.

Adipose tissue is a complex organ that stores energy, regulates body weight, governs thermogenesis, produces vital hormones, contributes to the endocrine profile of the body, facilitates pregnancy and lactation, regulates appetite, involved with innate immunity, helps with wound healing and hair cycling, regulates inflammation through association with immune factors, protects and cushions organs, and holds cells in place (de Sousa Neto et al. 2022). Not bad for something that gets blamed for fat thighs!

Knowing how and why fat cells contribute to your health can help you overcome diseases like type 2 diabetes (T2D), depression, Long COVID, cardiovascular diseases, hypertension and other metabolic disorders.

Who cares what happens when I get old anyway?

A word to young people who think they won't care because they will just die anyway. It is not the fear of dying that should motivate you; it is fear of being disabled and in pain for years and years due to metabolic disorders.

*Allison Y. (41 year old): "I have a 43 years old friend who is an overweight smoker. She has diabetes and high blood pressure. She recently had both feet amputated from deep diabetic ulcers on her feet that would not heal and turned septic. The ulcers almost killed her. Now she is struggling to use artificial limbs and usually relies on her wheelchair.

Another friend has had arthritis since he was in his early 20's. He started off overweight as a younger adult and then became obese. Now he is around 45 years old and in chronic pain. He can barely move without it causing pain. He needs a wheelchair or a walker to leave the house and can't drive or do many things for himself. He can't get the joint replacements he needs because of his weight; but he can't lose weight very easily because of his chronic pain, so it's kind of a bad cycle.

When you get to middle age it's pretty horrifying watching people your age become incapacitated. It has motivated me to eat better and take better care of my health."

What happens when you gain weight?

When you eat too much your body goes into metabolic overload due to the excess calories. Fat cells increase in both abundance and size during excess weight gain due to accelerated adipose remodeling (Wang et al. 2013, de Sousa Neto et al. 2022). Adipose remodeling also changes the composition of immune cells in the fat tissue. Unlike your latest kitchen remodel, this remodeling leaves your fat stores in worse shape. It impairs adipose tissue function leading to whole body metabolic disorders.

So why is my Grandma Jennifer 320 pounds and still healthy?

Some people are genetically lucky. About 10-25% of obese people are metabolically healthy. They can gain weight and their fat cells remain small and healthy. They seem to keep their insulin sensitivity when they gain weight (Blüher 2010).

This may come down to genetic differences. There are inflammatory and insulin signalling pathways in visceral adipose tissue (VAT). Some pathways are common to obesity and unrelated to insulin resistance while other pathways are common to both obesity and insulin resistance. The lucky people who gain weight and still remain insulin sensitive seem to lack some of the signalling pathways that lead to production of excess inflammation chemicals (Barbarroja et al. 2010). So they gain weight without increasing whole body inflammation.

If you have any signs of metabolic syndrome or excess inflammation you are not one of the fortunate people who can gain weight and remain robust.

Even if you are heavy and metabolically healthy, too much weight can play a toll on your joints and feet.

John Steuart Curry Baby Ruth 1932 oil on canvas.

The SHORT VERSION of How Fat Dysfunction Messes with Your Health

Click here to see references and more science in the LONG VERSION of Fat Gone Bad:

Adipose tissue dysfunction increases whole body inflammation (metainflammation) and results in development of MetS symptoms via several pathways including:

1) Energy causes fat cell growth.

When there is too much energy available from food and/or excess inflammation, fat cells start to grow. All that late night snacking and extra desserts cause accelerated adipose cell growth. They switch from small metabolically healthy fat cells to larger metabolically dysfunctional fat cells.

The larger mutant fat cells undergo epigenetic changes due to the excess energy and inflammation. They start producing inflammatory chemicals, called cytokines or adipokines, and emit more free fatty acids (FFAs).

2) Extra thick fat cells spew out inflammatory chemicals.

Changes in the type and amount of cytokines and FFAs produced by fat cells promotes macrophage infiltration and activation into the fat (adipose) tissue. Macrophages are immune cells such as white blood cells. They are attracted to the sweet inflammatory chemicals produced by the abnormal fat cells.

Normally, white blood cells are beneficial and attack viruses and bacteria. However, in this case the immune cells show up to the fat tissue, find nothing to do, get bored and cause problems by attacking and damaging healthy adipose cells. These trouble making immune cells also spew out MORE inflammatory chemicals or cytokines which attracts more immune cells to the area. This sets up a vicious cycle of inflammation.

3) Fewer new blood vessels mean fat cells get less oxygen.

Changes in fat cell cytokine production reduces the number of new blood vessels growing into the tissue. This decreases blood flow to the area. Adipose tissue starts to suffocate due to lack of new blood vessels and increased inflammation. As you may guess, low blood oxygen is bad. Fat cells start to die.

4) Low oxygen prompts LOX production.

The oxygen shortage causes fat cells to produce too much of the enzyme lysyl oxidase (LOX). Normally, LOX initiates links in collagen protein which helps to stabilize it. Too much LOX, however, makes fat cells stiff and scarred. Dead fat cells end up surrounded by a stiff fibrous network and other fat cells are unable to expand into the area. This lack of space to grow causes fat deposits to build up in less desirable areas like around the internal organs.

5) The toxic environment causes death.

More fat cells die due to damage from crazy Rambo want-to-be white blood cells and lack of oxygen. There is accelerated adipocyte death. Macrophages infiltrate further into adipose tissue to consume the dying cells or encase them in crown-like structures to protect surrounding tissue. You can actually feel this hard and painful tissue in areas with a lot of fat and inflammation.

6) Inflammation spreads.

The inflammation in the fat starts to spread to other tissues including muscle and brain. Brain inflammation causes cognitive issues like memory problems, loss of critical thinking skills and depression. Muscle inflammation causes delayed healing, aches, and lack of energy.

7) Inflammation causes oxidative stress.

Dysfunctional and dying adipose tissue triggers oxidative stress through increased production of reactive oxygen species (ROS). Oxidative stress is caused by an imbalance of ROS. ROS are produced by the body to help fight off viruses and bacteria. Some amount of ROS are good; when too many ROS are produced inflammation increases.

8) ROS activates the immune system. ROS activates inflammasomes which are part of the immune system. This can trigger autoimmune disorders like asthma and multiple sclerosis (MS).

Stop this cycle by reducing inflammation!

Old man lights a torch in a pamphlet commemorating a meeting about retirement funds in 1897.

Epigenetics is how the environment influence how your genes work. Your body reads the genes coded in DNA and uses that information to make different proteins. Epigenetic changes changes how your body reads the DNA. It can turn genes on and off as well as slow down or speed up genetic expression. This causes changes in the proteins your body produces. Epigenetic changes can be reversible and do not change your DNA sequence.

*Names and some minor identifying details in all stories in this website are changed to protect people's privacy.

This information is for informational purposes only and does not constitute medical advice, diagnosis, or treatment.

References:

Barbarroja N, López-Pedrera R, Mayas MD, García-Fuentes E, Garrido-Sánchez L, Macías-González M, El Bekay R, Vidal-Puig A, Tinahones FJ. The obese healthy paradox: is inflammation the answer? Biochem J. 2010 Aug 15;430(1):141-9. doi: 10.1042/BJ20100285. Abstract.

Blüher M. The distinction of metabolically 'healthy' from 'unhealthy' obese individuals. Curr Opin Lipidol. 2010 Feb;21(1):38-43. doi: 10.1097/MOL.0b013e3283346ccc. Summary.

de Sousa Neto IV, Durigan JLQ, da Silva ASR, de Cássia Marqueti R. Adipose Tissue Extracellular Matrix Remodeling in Response to Dietary Patterns and Exercise: Molecular Landscape, Mechanistic Insights, and Therapeutic Approaches. Biology (Basel). 2022 May 17;11(5):765. doi: 10.3390/biology11050765. Full article.

Wang QA, Tao C, Gupta RK, Scherer PE. Tracking adipogenesis during white adipose tissue development, expansion and regeneration. Nat Med. 2013 Oct;19(10):1338-44. doi: 10.1038/nm.3324. Full article.