0:00 - 4:21 - Intro
- What inspired this Podcast
- What is a fibroblast and a Phenotype?
- Why are we looking at Pulmonary Fibroblasts?
- What an Activated Fibroblast (Myofibroblast) is.
- When Myofibroblasts are beneficial and when they are not.
4:22 - 5:58 - How Myfibrobast create tension
- Myfibroblasts create contractures; this is what makes it muscle-like (-Myo)
- Anaconda Analogy
- Niek’s personal experience and inspiration
5:59 - 7:28 - The role of the Immunecentric Approach
- Today’s episode will mesh into the Immunecentric Approach. (IC Approach)
- The IC Approach is not a Way of Life; rather it’s a set of skillsets.
- The IC Diet —> 60-70% amelioration in tension and pain.
7:29 - 9:32 - What You need to know before we start
- Fibroblast to Myofibroblast Transition (FMT)
- When Fibroblasts change their uniform (phenotype)
- Activation tends to happen via TGF-Beta (TGF-b)
- Fibrosis defined.
- TGF-b is the radio signal that casues FMT
9:33 - - What this paper found
- Most scientists target TGF-b to limit fibrosis; works great in mice, not in humans.
- This team of scientists started targetting metabolic pathways instead and received a way better outcme in fibrotic amelioration.
- 2 reasons why this is so crazy; (1) Food, (2) Macrophages play a big role in FMT.
- We are going to dive deep and then spel out a solution
11:25 - 13:22 - Quick Breakdown of Metabolic Pathways in Fibroblasts
- How metabolism works within our cells
- TCA Cycle; Carb (OXPHOS) & Fat (B-Ox) Burning
- Glycoloysis; No Oxygen (O2), just sugar; precedes TCA Cycle
- Pentose Phosphate Pathway (PPP); DNA Precursors
- Glutaminolysis; Collagen Production
- de novo serine & glycine synthesis; Collagen production
13:23 - 15:19 - Warburg Metabolism and where else we see this pattern
- Activated Firoblasts use Aerobic Glycolysis; its a silly metabolic move.
-Where else we see this kind of metabolism; Cancer and M1 (Pro-Inflammatory) Macrophages; Warburg Metabolism
15:20 - 17:17 - Why would activated Fibroblasts do Warburg Metablism
- Rapid Production of ATP, fast but inefficient
- NAD Repletion can still continue, via lactate
- Feeds PPP and de novo glycine synthesis pathways
- PPP —> More Fibroblast Cells
- e novo glycine —> Collagen Production
- Energy, Fibroblasts and Glycine
- Quick Summary via Analogy
17:18 - 20:52 - What Warburg Metabolism does to drive fibrosis
- How FMT can traansfer via Mechanotransduction
- What happens under aerobic Glycolysis / Warburg Metabolism; lactate & succinate mve int ECM.
- Does 2 things; HIF-1 and TGF-b
- Acidifies the environment; stabilizes HIF-1.
- What HIF-1 does; quick analogy
- TGF-b = signalling molecule for FMT; acidifying the ECM drives up TGF-b
- TGF-b upregulates glycolysis; more gas power, fuel on the fire
- What this nets out.
- Everything Summarized
20:53 - 23:51 - The Third Player in the Mix; Macrophages
- Macrophages and Fibroblasts are Best Friends
- A quick breakdown on Macrophage terminolgy function across the Body using Analogy.
- How Macrophages relate to Fibroblasts and why the IC Diet is so impactful.
- Steering Fibroblasts away from FMT
- Use cases to target Fibroblasts via Macrophages
23:52 - 27:29 - Why is the Gut the Primary place to start?
- Quick review of the Influence of the Gut Lining; the gut is the inner skin; greatest reservoir of the Immune System lives here.
- How Fibroblasts play a role at the gut lining via Mechanics.
- There is both Mechanical and Biochemical conversations; both have influence.
- How You can start leveraging this.
27:30 - 30:11- The most common Client Profiles
- Most of the Population is Overweight, Insulin Resistant and / or has Gut Issues and what this means for Your Fibroblasts
- Why do You only have to have 1 of the 3 above; explanations for each.
- This activates Fibroblasts; never undergo apoptosis, this drives disease because the Body profiles as having a chronic injury.
- If Your Inflammed Your tight, If Your tight You’re going to be inflammed.
30:12 - 32:29 - Solution Set for the most common profile
- Cut off Glycolysis in both M1’s and Fibroblasts; Immunity Code Gut Protocols.
- Clear HIF-1, succinate and lactate; Immunity Code Niacin & 4-axis rotation
- Immunity Code Diet as Maintenance
- Could solve 60-70% of Your Problems.
32:30 - 34:45 - The second most common Client Profile
- Too much autophagy, overtraining, too hard on the Biohacking, wiry, sarcopenia
- You get creaky, slow, stiffer.
- History of too much fasting, overdoing biohacking, overtraining.
- Too many M2 (Anti-Inflammatory) Macrophages, Anti-Inflammatory Imbalance
- M2’s release TGF-b which activates the FMT
- This can come full circle and become Pro-Inflammatory.
34:46 - 38:17 - Solution Set for the second-most common profile
- Add Shikonin into Your Day 2 Supplement Stack
- Add Argemona mexicana (Prickly pear) into Your Day 2 Supplement Stack
- Add Fagonia cretica into Your Day 2 Supplement Stack
- All have been shown to slow FMT by targetting the metabolic Pathways
- - Add Resveratrol into Your Day 1 Supplement Stack; binds to the receptor of TGF-b to prevent TGF-b from transmitting it’s signal.
38:18 - - Additional Protocols and Close-Out
- Avoid taking Glutamine at the 24 hour mark; does not feed into Glutaminolysis and why timin is so important
- Add Glutamine within 1 hr mark of workout and why.
- Post Bodywork, combine with Niacin and 4-axis for HIF-1 Clearance
- Other additions Rutin, Orexin-A, Apigenin, Baicalin, Naringin
RESOURCES
The Paper that inspired this Podcast
Fascial Immunity Podcast
Shikonin - As chemical compound
