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Retrograde Signaling Explained

Published by Dr. Venn-Watson
Dr. Eric Venn-Watson’s Highlights
    • Retrograde signaling happens within cells and between them. 
    • This signaling helps keep our bodies in balance. 
    • Taking a supplement, like fatty15, can help your body produce more of a certain retrograde signaling mediator known as PDC.

Maybe you’ve never considered retrograde signaling, but you’ve probably wondered how your body maintains its balance. When it is well, everything about your body is in a state of homeostasis or balance. 

Part of that balance involves retrograde signaling. We’ll tell you what it is, why it’s important, and explain how a newly discovered endocannabinoid can help you achieve better balance in your own body. 

What Is Signaling?

You might not know it, but right now, there are millions of signals being transferred in your body every second. Inside each cell, signaling happens between the nucleus of the cell and the other organelles, like the mitochondria. 

Receptors located all over your body are also continually collecting data from external sources and sending signals to your brain, which then sends signals to other cells and receptors to help effectuate needed changes. 

Examples of Signaling

There are three different types of signaling in our bodies.

Chemical signaling. These types of signals happen inside the cell, between two cells via a gap junction or a synapse. This is how many of the cells in your body communicate, like hormones. Chemical signaling happens between cells.

Mechanical signaling. Mechanical signaling happens when an external source signals an internal response. An example is touching a hot stove. The hot stove is the external source that causes the sensory cells in your finger to react. 

Electrical signaling. This type of signaling involves the relay of electrical signals across cells. Electrical signaling controls functions like the rhythmic beating of your heart. 

          All of these signals help regulate functions in your body, so you are in a state of healthful balance.

          What Is Retrograde Signaling?

          When we study cell signaling, we often look at how one cell sends a message to another cell or how one organelle sends a message to another organelle within a cell. 

          Retrograde signaling, however, involves the sending out of a signal and its return to the original cell, kind of like a boomerang. 

          What Does Retrograde Signaling Do?

          Retrograde signaling is important in understanding neuroscience. In our brains, neurotransmitters rely on retrograde signaling to achieve homeostasis. 

          When one cell signals another, it sends a message that essentially asks, “How’s it going over there?” The other cell sends back a status report attached to the original message. The original cell then makes necessary changes or signals other cells for changes if they’re needed. 

          In more scientific terms, one neurotransmitter (the presynaptic neuron) sends out a signal received by the postsynaptic neuron. That postsynaptic neuron acts on the presynaptic neuron by firing back a reply in direct response to that signal. 

          This creates a feedback loop, and if you aren’t familiar with feedback loops, let’s talk about what they are and how they work. 

          The Role of Feedback Loops

          Feedback loops are the “end results” of the signaling process. For instance, if you touch a hot stove, the sensory cells in your finger send a message to your brain that the stove is hot, and your brain signals your muscles to move your finger away from the stove. 

          There are two different types of feedback loops. 

          • Positive feedback loops. Positive feedback loops send signals that increase behaviors or functions. Childbirth, for instance, is an example of a positive feedback loop that causes uterine contractions until the baby is born.
          • Negative feedback loops. These loops decrease activities in your body to restore balance. Thermoregulation (or core body temperature) is an example of negative feedback loops. 

          These loops are important for keeping our bodies balanced, and there’s a special system involved that plays a huge role in keeping this balance. 

          Retrograde Signaling in the Endocannabinoid System

          The endocannabinoid system is a complex system of receptors located in the body that regulate homeostatic function. The system comprises receptors known as CB1 and CB2 receptors. 

          Certain compounds, called cannabinoids, interact with these receptors to help effectuate necessary changes. Your body makes its own cannabinoids (called endocannabinoids) that bind to these receptors. 

          • Anandamide. Known as the bliss molecule, anandamide can only bind with CB1 receptors, so it’s not considered fully acting. 
          • 2-AG. These molecules can bind with both CB1 and CB2 receptors and are therefore thought to be fully acting. 

          These endocannabinoids help regulate synaptic transmissions by holding the retrograde signals from the postsynaptic neuron for tenths of seconds, helping maintain better signaling balance. 

          What does this mean for our health? Because the endocannabinoids help regulate these transmissions, we can experience: 

          • A good night’s sleep
          • Regulated appetite
          • Mood balance
          • Increased metabolic health

          For decades, we’ve only known the body can make two endocannabinoids. 

          Now, there’s a third. Pentadecanoylcanitine (PDC) is a newly discovered, fully-acting endocannabinoid. What’s great about this endocannabinoid is that it appears to be longer lasting in the body (2-AG metabolizes pretty fast) and has additional health benefits, like lowering some cytokine levels in the autoimmune, cardiovascular, neoplastic, pulmonary, and skin systems

          How Can You Help Your Body Make More PDC?

          Your body needs fatty acids to synthesize endocannabinoids and pentadecanoic acid (aka C15:0) to make PDC. C15:0 is an odd-chain, saturated fatty acid that has been recently recognized as an essential fatty acid. Further, science now supports that C15:0 is superior to even the purest and most effective form of omega-3.*

          Benefits of C15:0

          Unlike omega-3, which can oxidize and go rancid in your cells, C15:0 is a saturated fatty acid that is solid at room temperature and doesn’t oxidize. Overall, it’s better, broader, and safer for your body — here’s how:*

          • Better. When studied, C15:0 had more dose-responsive benefits than omega-3. C15:0 had 36, but omega-3 only had 10. 
          • Broader. Of the 12 cell types studied, C15:0 was able to repair 10 of them and prevent bad cells from proliferating. Omega-3 could only repair four and was found to be toxic to certain cells.
          • Safer. C15:0 was safe for all cell types, while omega-3 was toxic to four of them, including lung and blood vessel cells.

          In addition to being a better for your cellular health than omega-3, C15:0 helps improve mitochondrial function, which is important in intercellular retrograde signaling.* It’s also capable of binding to receptors called PPARs, located all over your body, increasing the cellular signaling your body is capable of and ensuring regulation of the systems that are governed by your PPARs.*

          How To Get C15:0

          C15:0 is primarily found in trace levels in whole-fat dairy products. However, simply increasing your intake of whole-fat dairy products comes with extra calories, sugars, and high levels of the "bad" pro-inflammatory even-chain saturated fats.

          Elevate your cells. Elevate your self.

          Buy Now

          A solution? Fatty15.

          Fatty15 is a breakthrough supplement born from scientific discovery, containing one pure ingredient, FA15™. Just 100 mg per day of this pure, vegan-friendly version of C15:0 is all you need to restore your circulating levels of C15:0, make more PDC, and enjoy a more balanced you!*

          Fatty15 for Cellular Signaling

          Making more endocannabinoids can help your body become better balanced through retrograde signaling. Taking fatty15 can support your body’s ability to make PDC, a fully-acting endocannabinoid to support cellular signaling.*

          Check out the fatty15 blog for more articles on cellular signaling, endocannabinoids, and what else you can do to support your cells at their level! 


          Cell Signaling: How Your Cells Talk To Each Other - Ask The Scientists

          Retrograde signaling by endocannabinoids\PubMed.NCBI.NLM.NIH.gov

          Retrograde signaling in the regulation of synaptic transmission: focus on endocannabinoids|PubMed.NCBI.NLM.NIH.gov

          Pentadecanoylcarnitine is a newly discovered endocannabinoid with pleiotropic activities relevant to supporting physical and mental health | Scientific Reports

          Profile photo for Eric Venn-Watson

          Eric Venn-Watson M.D.

          Eric is a physician, U.S. Navy veteran, and Co-founder and COO of Seraphina Therapeutics. Eric served over 25 years as a Navy and Marine Corps physician, working with the special forces community to improve their health and fitness. Seraphina Therapeutics is a health and wellness company dedicated to advancing global health through the discovery of essential fatty acids and micronutrient therapeutics.

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