Are you too thin suffering from chronic inflammation/autoimmune disease such as IBD or Th1/Th17 dominance? Obese? Do you have cancer?

If so, then there’s a good chance that STAT3 is contributing to your problems.

Intro

STAT3 is a protein that binds to DNA and increases expression of certain genes.

The STAT3 pathway is used by a variety of cytokines, hormones and growth factors to increase blood cell formation, immune cell development, stem cell maintenance and growth. However, chronic activation of STAT3 underlies various diseases or disorders, such as cancer or obesity (R).

The Benefits of STAT3

Mice with defective or less STAT3  develop insulin resistance (R).

Mice with disruption of neural STAT3 causes obesity, diabetes, infertility, and thermal dysregulation (R).

STAT3 in the liver contributes to the brain insulin action leading to the suppression of glucose production (R).

STAT3 is able to activate several pathways related to liver regeneration and acute inflammatory reaction after liver injury (R).

Less STAT3 can contribute to fatty liver disease, and STAT3 gene variants are associated with it (R).

STAT3 has some anti-cancer properties.  In particular, it’s needed for the anti-tumor effects of interferon alpha in Chronic Myelogenous Leukemia (CML) (R).

In obesity, chronic STAT3 is activated in the brain by increased leptin levels leading to the development of leptin resistance, whereas in the peripheral organs chronic IL-6-induced JAK-STAT3 impairs insulin action. We report the consequences of chronic JAK-STAT3 induced signaling as present under obese conditions in the main metabolic organs. (R)

Cells/tissues without STAT3 shows impaired pathogen response (R).

When cells completely lose STAT3 function people can develop excess IgE responses (R).

Mice lacking STAT3 specifically in the liver have insulin resistance and glucose intolerance when fed a high-fat diet and restoration of STAT3 expression in these mice corrected the  abnormalities (R).

STAT3 plays an important role in the induction of liver acute-phase genes in response to bacterial LPS (R).

STAT3 action in the mouse hypothalamus and liver appears essential for normal body weight and glucose homeostasis in response to the actions of both leptin and insulin (R).

The Negatives of STAT3

cancers-06-00926-g002-1024

STAT3 contributes to the development of IBD in mice and genetic studies (R).

Mice without STAT3 in T cells are resistant to animal models of multiple sclerosis (MS)(R).

Specifically, inhibiting STAT3 will inhibit Th1 and Th17 cells (R), which are immune cells involved in autoimmunity.

All in all, STAT3 plays an important role in autoimmune and inflammatory diseases and some cancers.

STAT3 produces pro-cancer products such as MMP-3, MMP-9, VEGF, HIF-1a, COX2, IL-6, IL-23 and ICAM1 (R).

The Thin/Inflammation Phenotype vs The Obese Standard American

shutterstock_301460216

A question I ponder sometimes is that the people who are thin in some ways are more likely to have inflammation problems.

There are many reasons for this.  For example, one reason I mentioned previously has to do with PPAR gamma.

STAT3 is another one of those proteins which if inhibited or if it’s not working right will cause insulin and leptin resistance and obesity.

On the other hand, if it’s over active, it will cause autoimmune conditions, inflammation, and cancer.

So STAT3 has good and bad properties.  You can look at your genes at the end.

Natural STAT3 Inhibitors

STAT3 Activators

STAT3 23andme Genes

shutterstock_300433304

Order your 23andme to see your genotypes.

rs744166 G/A

The A allele is presumably higher STAT3, as it increases autoimmune disease risk, but makes you thinner. About half of the alleles in a population are A.

There are a few studies showing a relationship between STAT3 snps and IBD (R).

  • AA=1.5X Ulcerative Colitis risk (R)
  • A=1.2X increased risk of Crohn’s (R)
  • G=2.22X increased risk of abdominal obesity, lower STAT3 (R) – Saturated fat intake exacerbated these effects; among all participants with the highest saturated fat intake (> or =15.5% of energy), people with GG had a 3.30X increased risk for obesity. (R)
  • GG=1.82X increased risk of Psoriatic arthritis, G=1.35X (R)

rs6503691 C/T

CC=more STAT3 production in people, (better for CML) (R).

C is the more common allele. About 33% of the alleles in a population are T.

rs9891119 A/C

C is higher STAT3.

A=lower STAT3, 2.5X more likely to have fatty liver disease (R).

A is the more common allele.  About 39% of the alleles in a population are C.

rs8069645 A/G

Probably G has higher STAT3.

G=increased risk of abdominal obesity (R).

About 31% of the alleles in a population are G.

Disclaimer and Caveats

FDA Compliance

The information on this website has not been evaluated by the Food & Drug Administration or any other medical body. We do not aim to diagnose, treat, cure or prevent any illness or disease. Information is shared for educational purposes only. You must consult your doctor before acting on any content on this website, especially if you are pregnant, nursing, taking medication, or have a medical condition.

HOW WOULD YOU RATE THIS ARTICLE?

1 Star2 Stars3 Stars4 Stars5 Stars 1 Total Votes Loading...
TWEET
0

4 COMMENTS

  • Luigi

    very interesting article, thank you. I have gastritis since 2006 (the NHS havent a clue why), and even ices only partially works on the location as of yet. I am waiting fro my 23andme results.

  • Dylan

    What would be the top 3 STAT3 inhibitors?

  • Phuong

    In you previous post about IL-10, you noted that Cayenne will increase IL-10. In this post, Cayenne block STAT3 which is include the activation of IL-6 and IL-10 , and IFN. I donot understand so much about this point.

    1. Joseph M. Cohen

      IL-10 can be increased in other ways. I’m not sure what you mean – post the studies.

  • Leave a Reply

    Your email address will not be published. Required fields are marked *