Updated: Feb 21
How chronic stress leads to weight gain.
The link between stress and weight gain has been well established in research and it may be why your diet and exercise plan are not achieving your desired results.
Stress is part of life and in small doses it can be good thing. It can increase motivation and mental focus so that you get the job done on time. But in our fast-paced lives, stress is relentless and excessive, and it comes in many forms.
A stressful event, or stressor, is not just an emotional trigger but can be anything that disrupts the body.
Stressors can be categorised as follows:
Regardless of its origin or cause, the effect stress has on the body is the same.
The Stress Response: Hypothalamic-Pituitary-Adrenal Axis
During a stressful event or trigger, signals from the stressor are detected in various regions of the brain and these signals converge on the hypothalamus. The hypothalamus integrates and interprets these signals and responds by activating the sympathetic nervous system (SNS) and also by releasing corticotropin-releasing hormone, CRH. CRH acts on the pituitary gland in the brain to secrete adrenocorticotropic hormone, ACTH, which then sends signals to the adrenal glands (small glands located above each kidney).
The combined resultsof SNS activation and CRH release, lead to the secretion of the following hormones from the adrenal glands:
Cortisol, a glucocorticoid and the main hormone responsible for the stress response. Cortisol is usually elevated in the morning and then reduces as the day goes on. It can fluctuate slightly during the day to help deal with short-term stressors and then returns to baseline. Overnight, cortisol is normally low to allow for a good nights’ sleep. Cortisol provides a negative feedback signal to the hypothalamus to stop producing CRH, which under normal conditions would result in a reduction in cortisol levels.
Aldosterone, a mineralocorticoid that regulates fluid balance and blood pressure. It is responsible for fluid retention that worsen in times of stress.
Noradrenaline and adrenaline, catecholamines that influence metabolism and the cardiovascular system. These hormones are responsible for the elevated heart rate that commonly comes with stress.
Cortisol – the stress (and weight gain) hormone
Cortisol is main the “stress” hormoneand when it comes to weight gain, it’s the hormone responsible for increasing visceral (deep) fat as well as the storage of stubborn fat around the abdomen and the upper arms.
In short-lived stress cortisol helps the body manage by:
1. Releasing glucose from protein stores in a process called gluconeogenesis. This provides energy in times of need.
2. Supressing immune activity (an energy-depleting state). However, in prolonged stress, cortisol actually increases immune activity and inflammation (see below).
3. Activating the sympathetic nervous system to increase metabolism and mental focus.
If stress is prolonged and cortisol remains persistently elevated, a number of detrimental processes occur, and these can eventually lead to fat gain.
Cortisol and the Gut-Brain-Weight Gain Connection
Most people have experienced gut “feelings” or “butterflies” during times of stress. This is because there are direct communication pathways between the brain and the gut via the blood stream, autonomic nervous system and the Vagus nerve (more on this pathway in “Faulty Gut-Brain=Weight gain”.
When it comes to stress, cortisol has been shown to produce a number of effects in the gut, and we now know that gut health is central to maintaining a healthy weight.
Research shows that stress, and persistently elevated cortisol, is associated with dysbiosis, leaky gut, inflammation, leaky brain, hormonal disruptions, metabolic abnormalities, cognitive dysfunction, mood disorders, sleep disturbances,
cravings and weight gain.
Cortisol alters gut function
As noted in previous posts and in “The Science” section of this website, any alterations in the gut microbiota or in the function of the gut wall can disrupt immune function and result in inflammation throughout the body and brain. Inflammation is the hallmark of hormonal, metabolic and neurological abnormalities that can ultimately lead to fat gain.
Cortisol is known to alter the composition of the gut microbiota (dysbiosis) as well as influence bowel movements, the secretion of digestive enzymes, the production of gut neurotransmitters and absorption of nutrients through gut wall.
Research has also shown that cortisol damages tight junctions between enterocytes leading to increased permeability of the gut wall, commonly known as leaky gut. A leaky gut allows molecules to cross from the gut lumen through the gut wall and into the blood stream where they activate immune cells and have the potential to cause inflammation throughout the body.
Cortisol contributes to inflammation
Another mechanism by which cortisol can lead to dysbiosis and inflammation is by activating the sympathetic nervous system (SNS). The SNS produces noradrenaline (NA), which has a similar action to cortisol in its ability to change gut motility, secretions and absorption. It also activates enterochromaffin cells (endocrine cells of the gut wall) to produce more NA.
NA is known to stimulate the growth of E. coli, a potentially pathogenic bacteria that is part of the normal gut microbiota. When E. coli numbers increase there is increased turnover of this bacteria and, as they die, they release lipopolysaccharide (LPS) from their cell wall. LPS is a highly inflammatory molecule that activates immune cells and has been found to initiate inflammation within a number of organs throughout the body, including adipose tissue and brain matter.
As discussed in “The Science” section of this website, inflammation within fat cells has been associated with metabolic and hormonal disorders, while inflammation in the brain can lead to increased appetite and disordered energy balance. Both inflammatory states can lead to weight gain and obesity.
It is important to note that inflammatory mediators in the brain trigger also the release of CRH from the hypothalamus. This ultimately leads to the release of more cortisol from the adrenal glands, therefore perpetuating the cycle.
Cortisol is associated with neuroinflammation
Cortisol has been associated with neuroinflammation – an inflammatory state in the brain that alters neurotransmitter production and therefore brain function. It does so either directly or indirectly.
Directly, cortisol damages tight junctions between endothelial cells that line the blood vessels of the blood-brain barrier, leading to gaps in the blood-brain-barrier, commonly termed leaky brain. Leaky brain allows LPS and other molecules present in the bloodstream to cross into the brain matter where they activate an immune response, resulting in neuroinflammation.
Indirectly, cortisol causes dysbiosis and leaky gut – a state that leads to inflammation throughout the body and within the brain matter (as discussed above).
Neuroinflammation has been associated with functional changes within various regions of the brain, one of which is an altered production of the neurotransmitters, serotonin, GABA, dopamine or melatonin. It also impairs the development of new neurons and neural pathways by reducing brain-derived neurotrophic factor, a protein crucial to the process. Various studies have linked these changes to cognitive dysfunction, insomnia, impaired appetite and energy control, mood disorders and weight gain.
Cortisol and Insomnia
Cortisol levels normally reduce as the day goes on and are at their lowest at night. If cortisol remains elevated at night, it can interfere with sleep. Research shows that insomnia or interrupted sleep can lead to weight gain through a complex cascade involving many hormones and neurotransmitters.
Melatonin is the hormone responsible for sleep and it is released from the pineal gland in the brain when the eyes are exposed to darkness. Melatonin synthesis relies on the presence of serotonin, which is a precursor molecule for its production.
Cortisol disrupts sleep by:
Causing leaky gut, which has been associated with reduced melatonin levels.
Altering the production of serotonin by enterochromaffin cells.
Activating the SNS which keeps us alert.
Reducing the production of GABA, the neurotransmitter of relaxation.
Contributing to neuroinflammation and therefore altering the production of melatonin.
It is important to note that sleep disturbances arising from any cause, such as sleep apnoea or the use of stimulants, can activate the stress response and elevate cortisol levels, leading to a vicious cycle of worsening sleep deprivation and increasing stress.
Cortisol and weight gain: other mechanisms
Cortisol increases insulin – the fat-storing hormone
In chronic stress, cortisol converts protein from muscles stores into glucose. This process is called gluconeogenesis and it provides energy to meet the extra demands that stress places on the body. If cortisol remains elevated for prolonged periods of time, so does glucose.
Glucose in the blood stream triggers the release of insulin from the pancreas, which helps it enter muscle and liver cells for storage as glycogen. These organs have a limit on the amount of glucose they can store, and any extra glucose becomes stored as fat. When glucose and insulin are persistently elevated, muscle and liver cells eventually stop detecting insulins signals. This is known as insulin resistance and is a pre-diabetic state associated with increased fat storage, inflammation and a number of metabolic abnormalities.
Cortisol moves fats between various body stores
Cortisol mobilises triglycerides from the liver stores and deposits them in visceral (deep) fat. This is the fat that is associated with metabolic syndrome, obesity and cancer.
Cortisol produces mature fat cells
Cortisol has been found to convert immature cells (progenitor, stem or undifferentiated cells) into mature, fat-storing fat cells. Researchers at Stanford University in California found that persistently elevated cortisol levels in mice, triggered a protein that converts undifferentiated stem cells into differentiated fat cells, resulting in weight gain. They also found that this mechanism increases the growth of existing fat cells.
Cortisol can lead to noradrenaline resistance
Another mechanism by which stress can result in fat gain is throughactivation of the sympathetic nervous system (SNS). The SNS produces noradrenaline, a hormone that increases metabolism and lipolysis, the breakdown of fat. When cortisol is persistently elevated, so is noradrenaline, and just like muscle cells become resistant to insulin, fat cells develop a resistance to noradrenaline. This means that the stress-induced noradrenaline response that initially causes fat loss, no longer works, however the fat-storing signals from cortisol and insulin remain highly effective.
This is why if stress is left unmanaged, it can override a healthy diet and regular exercise.
If you stress more, you will weigh more.
Reversing the damage
We are increasingly exposed to various stressors every day - they’re unavoidable – and chronic stress will not only lead to fat storage it will also counteract any efforts to shift stubborn fat. This is why stress-management is integral for successful weight loss.
As discussed in previous posts, a diet high in fibre and plant foods, along with targeted supplements can help restore gut health and reduce inflammation. Maintaining optimal gut health will help reverse dysbiosis and leaky gut, prevent LPS-induced inflammation and improve the production of gut neurotransmitters, therefore assisting with the gut-brain connection.
Some techniques that have been shown to help reduce cortisol and inflammation include
regular meditation, breathing exercises, yoga, tai chi, massages, walks in nature or just taking time out to rest each day.
It is equally important to reduce exposure to environmental, cosmetic, household and other toxins.
Also, speak to your medical practitioner about managing any sleep disorders, medical conditions, food allergens or modifying your pharmaceutical use.
The recommendations made in The Biome Protocol can help restore gut health, reduce inflammation and improve the gut-brain connection, therefore providing the physiological foundations that help manage certain stressors.
The following blogs have information on foods that may be helpful in reversing some of the damage caused by chronic stress.
1. Bahrami-Nejad Z, Zhao ML, Tholen S, Hunerdosse D, Tkach KE, van Schie S, Chung M, Teruel MN. A Transcriptional Circuit Filters Oscillating Circadian Hormonal Inputs to Regulate Fat Cell Differentiation. Cell Metabolism. 2018 Apr 3;27(4):854-868
2. Qaid, Mohammed & Abdelrahman, Mutassim. (2016). Role of insulin and other related hormones in energy metabolism- A review. Cogent Food & Agriculture. 2. 10.1080/23311932.2016.1267691.
3. Farzi, A., Fröhlich, E. E., & Holzer, P. (2018). Gut Microbiota and the Neuroendocrine System. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 15(1), 5–22
4. Huo R, Zeng B, Zeng L, Cheng K, Li B, Luo Y, Wang H, Zhou C, Fang L, Li W, Niu R, Wei H, Xie P. Microbiota Modulate Anxiety-Like Behavior and Endocrine Abnormalities in Hypothalamic-Pituitary-Adrenal Axis. Frontiers in cellular and infection microbiology, 2017 Nov 30;7:489
5. Petra AI, Panagiotidou S, Hatziagelaki E, Stewart JM, Conti P, Theoharides TC. Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation. Clinical Therapeutics, 2015 May 1;37(5):984-95. doi: 10.1016/j.clinthera.2015.04.002. PMID: 26046241; PMCID: PMC4458706.
6. Wang, H. X., & Wang, Y. P. (2016). Gut Microbiota-brain Axis. Chinese medical journal, 129(19), 2373–2380.
7. Smith, C. J., Emge, J. R., Berzins, K., Lung, L., Khamishon, R., Shah, P., … Gareau, M. G. (2014). Probiotics normalize the gut-brain-microbiota axis in immunodeficient mice. American journal of physiology. Gastrointestinal and liver physiology, 307(8), G793–G802.
8. Swanson GR, Gorenz A, Shaikh M, Desai V, Forsyth C, Fogg L, Burgess HJ, Keshavarzian A. Decreased melatonin secretion is associated with increased intestinal permeability and marker of endotoxemia in alcoholics. American journal of physiology. Gastrointestinal and liver physiology, 308(12), G1004–G1011.
9. Li, Y., Hao, Y., Fan, F., & Zhang, B. (2018). The Role of Microbiome in Insomnia, Circadian Disturbance and Depression. Frontiers in psychiatry, 9, 669.
10. Chao, A. M., Jastreboff, A. M., White, M. A., Grilo, C. M., & Sinha, R. (2017). Stress, cortisol, and other appetite-related hormones: Prospective prediction of 6-month changes in food cravings and weight. Obesity (Silver Spring, Md.), 25(4), 713–720.