Cytokines, SOCS-3 signaling: causes of high blood pressure, high cholesterol, & diabetes….
The Autocrine and Paracrine Roles of Adipokines. K Karastergiou Molecular and Cellular Endocrinology 2009 doi:10.1016/j.mce.2009.11.011
“The secretions of these engorged (fat) adipose tissue macrophages (immune fighting cells), such as IL-6 (interleukin) and TNFα (tumor necrosis factor-alpha) along with MCP (monocyte chemo-attractant protein) and leptin from hypertrophied (enlarged) adipocytes (fat cells) regulate the pathological changes of obesity, such as insulin resistance, and endothelial dysfunction.”
Diabetes, Metabolic Syndrome, and Obesity 2012; 5:175-189 online 7/8/12 I Spreadbury
Comparison with our ANCESTRAL DIET suggests dense ACELLULAR carbohydrates (no longer in the form in which it grows in the field = refined or processed starches) promote an INFLAMMATORY microbiota (the bacteria in our bowel) the primary dietary cause of LEPTIN resistance and OBESITY.
“…diet-related inflammation and evolutionary medicine. The obese guard their elevated weight…. In high-fat diet-induced obesity, leptin resistance is seen initially at VAGAL afferents, blocking the actions of satiety (feeling full) mediators, then centrally with GASTROINTESTINAL BACTERIAL-TRIGGERED SOCS3 signaling.” …. Due to being made up of CELLS, virtually all “ANCESTRAL” foods have markedly lower carbohydrate densities. Thus, the “forgotten organ” of the gastrointestinal microbiotica (BOWEL FLORA) is markedly changed by POSTPRANDIAL LUMINAL CARBOHYDRATE CONCENTRATIONS. … ACELLULAR flours, sugars, and processed food produce an INFLAMMATORY MICROBIOTA in the gastrointestinal tract with FAT effecting a “double hit” by allowing increased absorption of (INFLAMMATORY) POLYSACCHARIDES. A diet free of refined grains and full of whole foods with carbohydrate from CELLULAR tubers, leaves, fruits, and nuts produces a gastrointestinal microbiota consistent with our evolutionary configuration.
Google “SOCS3” search 7/8/12: “HGNC is the gene that encodes a member of the STAT-induced STAT inhibitor (SSI) also known as suppressor of cytokine signaling (SOCS). This gene is induced by INTERLEUKIN 6, interleukin 10, and INTERFERON gamma. The protein encoded by this gene can bind to JAK2 kinase.”
“Signal transducers and activators of transcription (STAT)-induced STAT inhibitor-1 (SSI-1) suppressor of cytokine signaling-1 (SOCS-1) suppresses TUMOR NECROSIS FACTOR alpha (TNF a) induced cell death. Y Morita et al Proc Natl Acad Sci 2000;97:5405-5410
Signal transducers and activators of transcription (STAT)-induced STAT inhibitor-1 [SSI-1; also known as a suppressor of cytokine signaling-1 (SOCS-1)] was identified as a negative feedback regulator of JANUS KINASE STAT signaling…. accelerated apoptosis… This sustains the activation of p38 mitogen-activated protein kinase (MAPK)… CYTOKINES play important roles in controlling … cell DIFFERENTIATION, PROLIFERATION ( STAT3 inhibition of NF-kB induced LVH is attenuated by IL 10), and APOPTOSIS, and these effects are mainly brought about by Janus kinase-signal transducers and activators of transcription (JAKSTAT) signaling. Activation of suppression of cytokine signaling (SOCS-1) is influenced by IL2, IL3, IL4, IL6, IL 13, granulocyste-macophage colony-stimulating factor, erythropoeitin, IFN-g…affect all 4 JAKs.”
Here is a printable version (pdf) of this handout, Cytokines signalling SOCS-3