Some people gain weight from chronic inflammation, while others lose weight.
The kind of inflammation you’re experiencing will determine if you gain or lose weight.
Most people will lose weight from chronic inflammation.
You might want to read the precursors to this post:
- A First Principles Approach To Obesity/Anorexia: The Big 4 Hormones
- 27 Hormones Involved in Weight Problems (not big 4)
- 29 Surprising and Science-Backed Ways To Lose Weight
The following list is different from the other posts. Believe it or not, there’s a lot more….
There’re many mechanisms in the body that alter appetite and energy storage and expenditure.
People who are over or underweight usually have a metabolic problem, assuming they’re trying to normalize their weight. And this metabolic problem is often from inflammation of various kinds.
CONTENTS [HIDE]
- Why Inflammation Leads to Weight Loss? – The Big Picture
- 5) C3a
- 6) MC4R and MC3R
- 7) STAT3
- 8) IL-10
- 9) TNF-alpha
- 10) IL-6
- 11) Nf-kB
- 12) Interferons (IFNy, IFNa)
- 13) IL-8
- 14) MyD88
- 15) IL-18
- 16) Quinolinic acid
- 17) Histamine
- 18) PAI-1
- 19) Orexin
- 20) Glutamate
- 21) Adrenaline (Epinephrine)
- 22) Norepinephrine (noradrenaline)
- 23) SOCS3
- 24) MMPs
- 25) IL-4
- 26) Serotonin
- 27) CNTF
- 28) GM-CSF
- 29) HMGB1
- 30) MIC1/GDF15
- 31) LIF
- 32) IL-11
- 33) TLR4
- 34) VEGF
- 35) NADPH
- 36) Prostaglandins
- 37) Nitric Oxide Synthase (NOS)
Why Inflammation Leads to Weight Loss? – The Big Picture
Cytokines suppress food intake in the brain (and also via the activation of projections of the vagus nerve to the brain (NTS)) (R).
The most significant mechanism by which inflammation reduces weight is by activating POMC neurons in the arcuate nucleus (ARC) of the hypothalamus (R).
POMC neurons in the ARC are activated by IL-1b and CNTF and this decreases food intake. POMC-containing neurons project to several different regions of the hypothalamus that have the melanocortin MC4 receptor and are involved in appetite regulation (PVN, LH, and VMH). These second-order neurons synthesize CRH that also inhibits food intake (R).
This inhibition of food intake can be significantly reduced by blocking melanocortin receptors (MC4R) (R).
You see, MSH and the MC4 receptors cause both an anti-inflammatory effect and also a reduction in appetite and weight loss (R).
The same thing goes with the nervous system. Inflammation activates the nervous system to reduce inflammation (negative feedback). But this will release CRH and cause weight loss.
So when you have a cytokine response, the body tries to reduce inflammation, and the same mechanisms by which it reduces inflammation also causes weight loss.
As long as you are having chronic inflammation (most common types), it will trigger the activation of these MC4 receptors and CRH and you will lose weight.
It’s critical to realize that psychological stress has the same effect as inflammation, which is why people often lose weight after chronic stress. When you get stressed, IL-1b is released and the same effects occur-activation of POMC neurons.
In CIRS, there is an additional mechanism by which the MC4 receptors are not being activated (because of low MSH and other mechanisms), so this is a unique chronic inflammatory issue that doesn’t necessarily result in weight loss – although it often does.
CIRS is characterized also by TGF-beta and the complement immune activation (C3a, C4a), which causes weight gain, especially when MSH is low.
It is clear that no single cytokine is responsible for the modulation of food intake. Instead, each cytokine along with other factors involved in metabolic function, such as insulin, CCK, and ghrelin, plays a role in a concerted response that ultimately leads to the inhibition of food intake through their actions on neurons in the hypothalamus.
1) Agouti-Related Protein (AgRP)
AgRP is a protein that potently promotes weight gain.
Agouti-related protein (AgRP) is a neuropeptide produced in the brain by NPY neurons in the arcuate nucleus in the hypothalamus. (R)
AgRP increases appetite and decreases metabolism and energy expenditure. It is one of the most potent and long-lasting of appetite stimulators (R).
So you eat more and expend less energy from increased levels of AgRP. Therefore you become fat from increased AgRP and thin from decreased levels.
AgRP is decreased after acute stress (R). This is a large reason why people lose weight after a very stressful period.
Interestingly, some people will gain weight following a period of stress, while others will lose weight.
There are many factors taking place, but some of the main ones in involved are cortisol, NPY, and AgRP.
People who gain weight may be more likely to have higher NPY and cortisol, which increase in response to stress and cause appetite stimulation and produce more fat cells.
On the other hand, people who lose weight probably don’t have as much NPY and cortisol and may also experience a larger drop in AgRP. A drop in AgRP from acute stress will make you thin.
People suffering from chronic inflammation will have lower AgRP.
Higher cortisol is a signal that IL-1b is elevated in the hypothalamus.
IL-1beta inhibits the release of AgRP from hypothalamic tissue (R).
The appetite-stimulating effects of AgRP are inhibited by the hormone leptinand activated by the hormone ghrelin (R). Ghrelin significantly increased AgRP in the presence, but not absence, of Glucocorticoids (R).
It has been found that AgRP stimulates the HPA axis to release ACTH, cortisol, and prolactin. It also enhances the ACTH response to IL-1-beta (R).
AgRP has been demonstrated to block (inverse agonist) MC3-R and MC4-R (R).
When activated, MC3- and MC4 receptor activation help people lose weight. These receptors are activated by the peptide hormone α-MSH (melanocyte-stimulating hormone).
Whereas α-MSH acts broadly on most members of the MCR family (with the exception of MC2-R), AGRP is highly specific for only MC3-R and MC4-R.
In the adrenals, AgRP blocks α-MSH-induced secretion of cortisol in mice (R).
Loss or gain of AgRP function may result in inadequate adaptive behavioral responses to environmental events, such as stress, and have potential to contribute to the development of eating disorders (R).
Some studies suggest that inadequate signaling of AgRP during stress may result in binge eating (R).
Leptin suppresses food intake and increases energy expenditure at least partially by suppressing AgRP (R).
Recent studies have shown that autophagy plays a key role in the regulation of food intake and energy balance in maintaining neuronal AgRP levels (R).
Cortisol (Glucocorticoids) increases AgRP (and NPY) gene expression in the arcuate nucleus through increasing AMPK (R).
Autophagy takes place while sleeping, so it’s important to get good sleep. An Infrared Sauna can also increase autophagy.
If you’re thin, it means you have low AgRP and you need to reduce your stress levels.
If you’re overweight, it means you have high AgRP and you need more sun.
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