Collagens in Energy Metabolism and Metabolic Diseases

Function of Collagens in Energy Metabolism and Metabolic Diseases | Open Access | OMICS Publishing Group

This article shows a link between collagen production and energy problems associated with Metabolic Diseases. Could this be a new avenue of research?

Defining the cellular sources of collagens in the normal and diseased states of the above metabolic tissues is thus critical to understanding metabolic disease. Under certain pathological conditions, the excess accumulation or collapse of collagens may disrupt normal cell-cell interactions, and cause the loss of tissue compliance or elasticity.

Finally, these disruptions of collagens result in tissue dysfunction such as atherosclerosis of the blood vessels, pulmonary fibrosis, liver cirrhosis and fibrosis in other organs.

This review will focus on the role of collagens in metabolic tissues, and attempt to summarize the function of collagens in energy metabolism. 

For a more general overview of collagen and its functions, see reference page:
Connective Tissue and Collagen Basics


The main components of the interstitial matrix and the basement membrane in the extracellular region of animal tissue are referred to as the extracellular matrix (ECM). The ECM plays important roles in providing support and anchorage for cells, regulating intercellular communication, and storing a wide range of cellular growth factors [1]. Thus, the rapid and local growth factor-mediated activation of cellular functions are triggered by changes in physiological conditions, without de novo synthesis

The ECM is tissue specific in quality and quantity. Components of the ECM are secreted from the intracellular region of resident cells via exocytosis. The main components of ECM are the interlocking mesh of fibrous proteins and glycosaminoglycans (GAGs). Furthermore, the main fibrous proteins are collagens, of which 29 types have been reported . The functions of these proteins include protection and support, and forming connective tissue, tendons, bone matrices, and muscle fiber.

Collagen proteins are large and complex, with multiple distinct domains, and are highly conserved among different species. Almost all collagen proteins are glycoproteins, protein cores made in the rough endoplasmic reticulum, and posttranslationally modified by glycosyltransferases in the Golgi apparatus. After being secreted into the ECM as precursors via exocytosis, they need a complex processes such as the cleavage of N- and/or C-propeptides which occurs via highly specific proteinases and then become mature collagens

Skeleton muscle and tendon

The ECM in skeletal muscle is organized in different levels, and collagens are the most abundant structural components of skeletal muscle ECM. 1% to 2% of muscle tissue and 6% of the weight of muscles are collagens

In tendons, the tendonosis occurs when the fibrous material collagens in a tendon begins to degenerate. This may occur as the result of injury. The tendon becomes tangled, weak and jelly-like when collagen degenerates. Additionally, muscular dystrophies are also associated with changes in matrix

Collagens play critical roles in force transmission and tissue structure maintenance in tendons, bone and muscle. It is well known that the contractile filaments in skeletal muscle are important to force development, and the tendon tissue transform this developed force from the muscle to the bone. In addition, collagens also play a role in the skeleton muscle development.

Smooth muscle cells and cardiac muscle cells

Vascular smooth muscle cells (VSMCs) normally reside in the media of the artery, lined with endothelial cells, and are surrounded by a specialized thin sheet-like structure of extracellular matrix components, including collagen types I, III, IV and V et al

Production of a functional matrix in SMCs requires the coordinated expression, modification, process of the ECM proteins, and some others signals such as PDGFß, EDG1 and TGF-ß that are involved in the processing and assembly of most ECM networks, including basement membranes, elastic fibers, and large proteoglycan matrices.

Additionally, the roles of collagens in heart, especially in the heart remodeling, have attracted enormous attention recently. The components of cardiac ECM are composed of fibrous proteins and glycosaminoglycans (GAGs). Fibrous proteins such as collagen and elastin serve as reinforcements for the myocardium. GAGs such as glycoproteins and proteoglycans function as the space-filling concrete in the heart.

The mechanical support for pumping blood in the heart is also provided by Collagens

A number of muscle and related pathologies involve changes in matrix properties

This is the first hint I’ve seen linking EDS muscle problems/pain to collagen production in the ECM.

Cell signal pathway

This is where things get interesting:

The diverse array of collagens not only provide the physical structure of the cell, but also various biological functions largely through them to bind many other interacting partners such as growth factors, other ECM proteins, signal receptors, and adhesion molecules like integtrins.

The collagens perform profound effects on cell fate and behaviors via interacting with the surface receptors and growth factors and then transduce to cytoplasmic signal pathways

The collagens can collaborate with their receptor integrins, growth factor receptors and intracellular signals to regulate gene expression associated with metabolic cell growth, differentiation, survival and glucose uptake


Metabolic diseases continue to be a major health challenge of pandemic proportion in the world. They can be caused by lifestyle or genetic variants, leading to the dysfunction of energy balance through a complex pathophysiological process. The ECM remodeling and tissue destruction are required during these complex process. Lots of component increases, decreases or modifications are involved in ECM remodeling, especially collagens remodeling. With the current level of research and increasing understanding of the function of collagens, there is hope that better medications will emerge to control complex metabolic diseases.

It is well-known that extracelluar signals including growth factors and cytokines bind to specific receptors on the surface of their target cells. Recently, more and more findings were reported that collagen not only builds the main structural components among the cells, but also covalently anchors to the plasma membrane of the cells to enhance the efficient binding between the cytokines and their specific receptors, thereby modulating their mitogenic and angiogenic effects on different types of cells

The newly recognized importance of collagen may finally stimulate more research into connective tissues of all kinds, and the production defects caused by EDS.

Additionally, the recent discovery of additional functions of collagen, not just as a support structure, but an active agent of changes in other kinds of cells may finally provide an explanation of more of the stranger symptoms of EDS.

Obviously, the ECM components, especially the collagens, will be recognized as the key regulators in cell physiological activities in future.

On her blog,, Kendra continues where this article leaves off, and gives a better explanation of the interrelationships and consequences when things go awry:





15 thoughts on “Collagens in Energy Metabolism and Metabolic Diseases

  1. Zyp Czyk Post author

    I had no idea how popular this article would be, and I’m happy that you find it useful.

    I always assumed collagen was just this passive framing material in the body, so I was surprised how far reaching its effects can be. In nature, everything really is connected to everything else!

    Liked by 1 person

  2. Strength/Flexibility/Health/EDS

    Reblogged this on Strength/Flexibility/Health/EDS and commented:
    How and what does Natural Movement Training (NMT) have to do with Ehlers-Danlos Syndrome (EDS), or more specifically collagen and connective tissue? I have to say .. a lot.

    Natural Movement Training makes so much sense to me. It just does and probably because the whole approach is based on how humans used to move… you know, before we had all modern conviences and didn’t have to leave our house, beds and computers to do ANYTHING?
    I also just feel better when watching many of the NMT videos on YouTube, because I can see the muscles that hurt and need strengthening in my body, really work. And I mean work, versus what usually happens in any of my typical workouts.

    Anytime a topic that can somehow be tied back to NMT comes up, I’ve talked about it. I even bought Dr. Francomano a copy of “Move your DNA” and gave it to her as a gift when I saw her last week. One person that I’ve spoken to quite a bit about NMT and who also is reading “Move your DNA,” is one of my co-admins for the Facebook Group, EDS Athletes. Donna, my co-admin, is a paraolympian, has a blog called “Beating Limitations” ( and seems to like reading, researching and applying new information that just makes sense, as much as I do.

    One of the things that Donna recently shared with me, was this article on Collagens in Energy Metabolism and Metabolic Diseases from another EDS blog (

    Here are the reasons she shared this with me and why this info is pertinant to what we’ve both been reading in “Move your DNA,” but is also important for those of us living with EDS.

    Point #1 – A lot of what “Move Your DNA” discusses in the beginning of the book is about the exocellular structure. Exocellular means what happens on the outside of a cell and not just inside (see Wikipedia for a more detailed explanation: and how those situations can affect the overall function and expression of a cell in our bodies.

    You are probably wondering what does this have to do with EDS, collagen and connective tissue cells? See point 2 below:

    Point # 2 – It’s important because collagen is not only involved in the structure (ie. building blocks) of the cell, but also in the way cells communicate to each other. Read this:

    “Defining the cellular sources of collagens in the normal and diseased states of the above metabolic tissues is thus critical to understanding metabolic disease. Under certain pathological conditions, the excess accumulation or collapse of collagens may disrupt normal cell-cell interactions, and cause the loss of tissue compliance or elasticity.”

    So, how can the issues of excess accumulation, collapse of collagen protiens and disruption of normal cell-cell interactions on the outisde affect a connective tissue cell?

    Point #3 – Disruptions in cell-cell interactions (ie. the way cells “talk” to each other) because the collagen proteins have piled-up & collapsed, causing the connective tissue cells to not be able to “talk” to each other, results in issues in our tissues, literally. And these issues mostly occur on the outside of the cell. Read below:

    “Finally, these disruptions of collagens result in tissue dysfunction such as atherosclerosis of the blood vessels, pulmonary fibrosis, liver cirrhosis and fibrosis in other organs.”

    Can you see how issues that stop collagen proteins from doing their job properly and prevent them from talking to each other on the outside of a connective tissue cell, can affect the overall “health” and function of our connective tissues?

    Just read Wikapedia’s definition of EDS to see how these issues can either cause EDS. Or, think about how non-inherited issues could possibly affect the severity of our EDS symptoms: “Ehlers–Danlos syndrome (EDS) is an inherited connective tissue disorder with different presentations that have been classified into several primary types. EDS is caused by a defect in the structure, production, or processing of collagen or proteins that interact with collagen, such as mutations in the COL5A or COL3A genes (See Wikapedia’s deffinition for Ehlers-Danlos Sydrome to read more).”

    Collagen proteins are just like the bricks used to build your house. Many things can affect how well the bricks are placed, if they are placed correctly and how strong they all are once the your house is built. In addition, there could have been issues with the way the bricks were made that will affect their structure or their function once put together to build your house. Any of these issues can result in a some pretty serious structrural problems that stem from your house being built with faulty bricks.

    Finally, what does the book, “Move you DNA” & NMT have to do with all of this? “Move your DNA” pushes you to think about genetic and non-genetic exocellar issues that can affect the structure and function of our cells and thus, our connenctive tissues. Numerous points are made about how focusing on healthier, more natural lifestyle choices, such as strenthening our bodies through natural movements, can help improve the structure, function and stability of our tissues, even if they were built with a genetic defect.

    To read more about how collagen issues can affect our connective tissues, you can read the blog post that I just summarized by reading this link:

    And to read the original article that reviews the role of collagens in metabolic tissues, and attempt to summarize the function of collagens in energy metabolism, you can click the link below:


    1. Zyp Czyk Post author

      Thanks for more fully explaining this article – even I understand it better now!

      However, I can’t find your blog article – all pages are “not found” and I can’t see anything except a sparse “landing page”. What is the link to your blog entries? I’m very interested to see what else you are posting.


    2. Zyp Czyk Post author

      I found the problem: there seem to be two blogs, one on WordPress and one with its own domain. The links here point to, while the actual blog seems to be at

      Liked by 1 person

          1. Kendra Neilsen Myles

            oh thank you! I’ve been so worried, because I went to go comment on this post last night, but then I realized that the blog post I wrote for my own blog was actually was posted as commment to yours. I still have no idea why or how it did that. My OCD got to me, as I was trying to figure out a way to delete this big comment that I accidently made on your very neat website and blog post. Needless to say, I’m so, so sorry. However, I’m glad to hear that you liked the post I wrote and that you liked my site! Thank you. Still some things to put together, but in time…


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