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SKIN BARRIER - PART II. WHAT ELSE DO YOU NOT KNOW ABOUT THE HYDROLIPID BARRIER?

Updated: Nov 16, 2023

The role of the epidermal barrier and its associated changes cannot be underestimated when it comes to the development of various dermatoses. From atopy to inflammatory conditions and recurrent discoloration, understanding the epidermal barrier is crucial.

In the previous post, we focused on the lipids within the stratum corneum. Now, let's shift our attention to the Skin Surface Lipids (SSLs) - the lipids present on the skin surface. These include sebum and other components that work together with the stratum corneum to form our hydrolipid film. We will explore both the well-known and lesser-known functions of this film. The final part of this series will delve into the practical aspects for cosmetologists, including treatments and home care products that aid in the regeneration of the epidermal barrier. Understanding epidermal lipids is crucial for the therapy and care of all skin types, as imbalances in their composition can lead to various skin problems.



 

Sebaceous glands and sebum production - a closer look at their intricate functions

Sebaceous glands are closely associated with hair follicles. Their quantity remains constant throughout our lives, and their activity is regulated, in part, by hormones. While the highest concentration of sebaceous glands is found on the face and hairy skin, they are not limited to those areas. Meibomian glands, for instance, are present on the eyelids. Sebaceous glands are typically connected to the hair follicle, except within mucous membranes. Structurally, they consist of acini, which can be singular or multiple. It is important to familiarise ourselves with the concept of a sebocyte - the secretory cell of the sebaceous gland. Cytologically, a sebocyte is a modified keratinocyte. Sebaceous gland cells differentiate from stem cells towards the center of the acinus, with some progeny cells synthesising lipids. As they mature, they enlarge significantly compared to their original size, around 100-150 times. Sebaceous glands are classified as holocrine glands, meaning that mature sebocytes undergo apoptosis, releasing their secretion, or sebum. Muscles attached to the hair follicles aid in the "squeezing" of sebum onto the skin surface. This entire process takes approximately a week, a crucial piece of information for determining treatment intervals. The gland duct is lined with stratified squamous epithelium, and excessive keratinization of the gland orifice can contribute to the formation of blackheads.

The distinction between sebum and oil is not entirely clear, as some sources use these terms interchangeably. However, other researchers explain that sebum refers specifically to the oil that has reached the skin surface, mixing with remnants of Natural Moisturising Factor (NMF) and epidermal lipids, as well as sweat.

Functions of sebum:

1. Protection against oxidative stress by transporting vitamin E to the skin surface

2. Antibacterial action through IgG

3. Expression of antibacterial peptides and proinflammatory cytokines

4. Regulation of neuropeptides

5. Protection of keratinocytes against UVB radiation

6. Maintenance of the integrity of the skin barrier

7. Regulation of steroidogenesis and local synthesis of androgens.

Sebaceous glands perform a wide range of functions, with the prevention of transepidermal water loss (TEWL) being the most well-known and understood. Most people associate sebum with negative effects due to its excessive secretion. However, deficiencies in sebum secretion also have negative consequences, as evident from the functions mentioned above.

Sebum secretion is hormonally stimulated but influenced by various factors such as age, gender, and the concentration of vitamin D3. Interestingly, individuals with acne have more innervated sebaceous glands, characterized by elevated levels of nerve growth factor (NGF).

It is essential to note that sebaceous glands are rich in receptors, including:

1. Steroid receptors (androgen and progesterone receptors)

2. Thyroid receptors (including alpha and beta estrogen receptors)

3. RAR-alpha, -gamma receptors, RXR-alpha, -beta, and -gamma receptors

4. Melanocortin 1 and 5 receptors

5. Opioid receptors

6. Cannabinoid receptors 1 and 2

7. Histamine type 1 receptors

8. Receptors for endothelial growth factor

9. Receptor for fibroblast growth.


 

KNOWLEDGE OF LIPIDS AND THE EFFECTIVENESS OF SKIN THERAPY.

Understanding lipids and their role in skincare is crucial for cosmetologists and skin therapist. While regulating sebum secretion is a common practice, addressing lipid deficiencies and damaged skin barriers requires a different approach. By comprehending the specific composition of lipids in different skin layers, we can make informed decisions in our treatments.

Previously, it was thought that increased sebum production was a primary factor in acne-related inflammation. However, recent findings indicate that the composition of sebum plays a more significant role than its quantity. Patients with acne often have lower levels of linoleic acid, which is crucial for preventing comedone formation. This component ensures the proper development and adhesion of corneocytes in the sebaceous gland ducts. Conversely, elevated levels of oxidised squalene stimulate keratinocytes to produce pro-inflammatory cytokines.

Beneath the concept of sebum, we find a mixture of lipids from various sources: epidermal lipids and the secretion of sebaceous glands. These lipids combine with hydrophilic components like sweat and residual NMF to form a W/O emulsion, with sterols acting as emulsifiers.

While ceramides dominate the lipids in the stratum corneum, glycerides are the most abundant in sebum. These glycerides, esters of glycerol and higher fatty acids, are considered essential fatty acids. It's worth noting that they are widely used in many creams, such as Caprylic/Capric Triglyceride derived from coconut oil, due to their popularity and effectiveness.

Glycerides, also known as acylglycerols, are a well-known group of lipids. Among them, diglycerides play a crucial role in intercellular signalling. On the other hand, triglycerides are the most abundant glycerides found in sebum. Cutibacterium, a bacterium, breaks down triglycerides into glycerol and fatty acids, thus leading to reduced levels of triglycerides in individuals with acne. Interestingly, triglycerides have recently been discovered to have the ability to extract lipids from the outermost layer of the skin, the stratum corneum, by anchoring themselves to its surface.

Squalene, a chemical substance first described in 1966 but known since the early twentieth century, is a polyunsaturated hydrocarbon and a triterpene belonging to the lipid family. It is often confused with its derivative, squalane, which is a popular ingredient in cosmetics. Squalene plays a significant role in cholesterol synthesis, making it essential for the biosynthesis of steroid hormones.

The structure of squalene resembles other substances like beta-carotene, coenzyme Q10, and vitamins E, K, and D, and it possesses antioxidant properties. However, squalene itself can undergo oxidation. The presence of oxidised squalene on the skin serves as an indicator of environmental pollution, exposure to heavy metals, and other harmful compounds found in smog and cigarette smoke.

As cosmetologists, we value squalene as a component of sebum because its excess can impede the fluidity of sebum, making it challenging for it to leave the sebaceous gland and contributing to the formation of blackheads. This sheds light on the importance of using local antioxidants and UV filter creams, as they can influence the composition of sebum and the functionality of our hydrolipid barrier. It is worth noting that squalene is produced by sebaceous glands and, unlike wax esters, is not present among subcutaneous lipids.


FREE FATTY ACIDS

Free fatty acids on the surface of the epidermis have different origins: either they are produced by sebaceous glands, or they are a product of the hydrolysis of triglycerides by bacterial enzymes.

The more we learn about lipids, the more impressed we are by them. Fatty acids and their proportions are crucial for the health of our skin. They are responsible, among other things, for maintaining acidic pH on the skin's surface, which is important for the homeostasis of the skin and the environment, necessary for the proper microbiota. Fatty acids are also converted by lipoxigenases into bioactive mediators, including eicosanoids, which play an important role in the course of skin inflammatory reactions.

Among the fatty acids, we can also find sapienic acid, which occurs in nature exclusively in human sebum (hence the name). It is attributed with antibacterial function. It is the most abundant fatty acid in our sebum.

Another important fatty acid for our skin is linoleic acid, as its proper level determines the appropriate consistency of sebum. With a deficiency of linoleic acid (and an increase in oleic acid, with which the body tries to replace the missing acid), sebum becomes harder and less fluid, which can have comedogenic effects. Linoleic acid also has photoprotective activity, as it can absorb UV radiation. Moreover, it has been discovered that the oxidation process of linoleic acid in the sebaceous gland affects the synthesis of waxes and sapienic acid.

Linoleic acid and gamma-linolenic acid belong to exogenous essential fatty acids, and if we do not provide them with an adequate supply through diet/supplementation, our skin will suffer. Many studies have shown that individuals with acne have lower levels of fatty acids compared to individuals with healthy skin. In the group with reduced FFA content, increased amounts of wax esters and cholesterol, as well as triglycerides, were also observed.

In recent years, many new studies and articles have described the relationship between diet and the composition of fatty acids in sebum. Researchers have been intrigued by the fact that in some societies living in non-urbanized areas and relying on a simple, unprocessed diet, which practically does not include saturated fatty acids, trans fats, high glycemic index carbohydrates, sugar, and cow's milk, acne problems do not occur at all. Therefore, it is crucial for a cosmetologist to have an interdisciplinary approach to skin problems and to recognize nuances and dependencies between the condition of the skin and the functioning of all other systems in our body.

The fatty acids contained in sebum should be perceived by us as part of a larger metabolic network that we are constantly getting to know and understand better, thanks to which we can increasingly effectively control inflammatory reactions and improve the condition of the skin in its various pathologies.

STEROLS AND THEIR DERIVATIVES

As mentioned earlier, cholesterol functions as an emulsifier in the emulsion that is the hydrolipidic film. Cholesterol itself is formed through the transformation of squalene, which is later used as a substrate for the production of steroid hormones such as vitamin D and certain androgenic and estrogenic sex hormones. Skin steroidogenesis is one of the most important determinants of properly functioning skin, and its disorders play a significant role in the etiology of many inflammatory diseases such as common acne, rosacea, and atopic dermatitis. Antagonists of receptors for these hormones in the skin hold great promise in the context of acne and androgenic-type alopecia therapy. Clinical trials are currently underway for a new drug called Clascoterone.

WAX ESTERS

Waxes and their esters are produced exclusively by sebaceous glands. No other cells in our body can do this. We are still learning about the synthesis pathways of these compounds and the enzymes responsible for them. However, it is known that wax biosynthesis occurs in correlation with sebocyte differentiation. Waxes on the skin serve a similar function as the wax on fruit skin - they simply create a protective, waterproof layer that prevents TEWL. Waxes are more resistant to oxidation and hydrolysis than squalene or triglycerides. They are also more resistant to high temperatures. An interesting phenomenon associated with waxes is the "lotus effect", which was first observed on lotus plants. This is a colloquial term for the self-cleaning phenomenon of the surface, where wax not only repels water but also anything that slides off its surface.

 

SUMMARY

In this blog post I uncovered the essential elements of the skin's epidermal barrier, including sebum, sterols, wax esters and free fatty acids, but that's not all!

In my upcoming blog post I will dive into the skin microbiome and explore how it impacts the aging of the skin barrier and its antibacterial functions.

A.


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