STAT3

STAT3 is a protein that binds to DNA and increases expression of certain immune genes that can cause inflammation that leads to autoimmunity, but also fight infections. 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).

Read: Natural STAT3 Inhibitors

The STAT3 gene is part of a family known as the STAT genes. These genes provide instructions for making proteins that are part of essential chemical signaling pathways within cells. When STAT proteins are activated by certain chemical signals, they move into the nucleus and attach (bind) to specific areas of DNA. By binding to regulatory regions near genes, STAT proteins can regulate whether these genes are turned on or off. STAT proteins are called transcription factors on the basis of this action. The STAT3 protein is involved in many cellular functions. It regulates genes that are involved in cell growth and division, cell movement, and the self-destruction of cells (apoptosis). The STAT3 protein is active in tissues throughout the body. It plays an important role in the development and function of several body systems and is essential for life. In the immune system, the STAT3 protein transmits signals for the maturation of immune system cells, especially T cells and B cells. These cells help control the body's response to foreign invaders such as bacteria and fungi. In addition, the protein is involved in the regulation of inflammation, which is one way the immune system responds to infection or injury. In the skeletal system, the STAT3 protein is involved in the formation of specialized cells that build and break down bone tissue. These cells are necessary for the normal development and maintenance of bones.

STAT3 (Good):

• helps with insulin sensitivity (R).
• when chronically elevated will cause obesity (R).
• suppresses of glucose production (R).
• helps with liver regeneration (R).
• helps reduce fatty liver disease (R).
• has some anti-cancer properties, especially for CML (R).
• helps clear pathogens (R).
• suppresses IgE responses (R).

STAT3 (Bad):

• STAT3 contributes to the development of IBD (R).
• can help cause multiple sclerosis (MS)(R).
• creates Th1 and Th17 cells (R), which are immune cells involved in autoimmunity.
• produces pro-cancer products such as MMP-3, MMP-9, VEGF, HIF-1a, COX2, IL-6, IL-23 and ICAM1 (R).

The STAT3 gene is part of a family known as the STAT genes. These genes provide instructions for making proteins that are part of essential chemical signaling pathways within cells. When STAT proteins are activated by certain chemical signals, they move into the nucleus and attach (bind) to specific areas of DNA. By binding to regulatory regions near genes, STAT proteins can regulate whether these genes are turned on or off. STAT proteins are called transcription factors on the basis of this action.

The STAT3 protein is involved in many cellular functions. It regulates genes that are involved in cell growth and division, cell movement, and the self-destruction of cells (apoptosis). The STAT3 protein is active in tissues throughout the body. It plays an important role in the development and function of several body systems and is essential for life. In the immune system, the STAT3 protein transmits signals for the maturation of immune system cells, especially T cells and B cells. These cells help control the body's response to foreign invaders such as bacteria and fungi. In addition, the protein is involved in the regulation of inflammation, which is one way the immune system responds to infection or injury. In the skeletal system, the STAT3 protein is involved in the formation of specialized cells that build and break down bone tissue. These cells are necessary for the normal development and maintenance of bones.

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

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

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 overactive, 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

• Spices/²-Caryophyllene oxide (in black pepper, cinnamon, clove, lemon balm, oregano, cannabis, rosemary, hops),
• Fish oil (R),
• Silibinin (R) – Milk Thistle 
• Bilberry (R),
• Black Cumin Seed Oil / Thymoquinone (R),
• Olive oil (extra virgin) (R),
• Zinc (R) (constitutive=always active),
• Lithium (R) (constitutive),
• EGCG (R) (constitutive),
• Curcumin (R) (constitutive),
• Broccoli sprouts/Cruciferous veggies/Sulforaphane (R),
• Cayenne/Capsaicin (R)