Adipocytes can produce antimicrobial peptides

Love your fat cells!

Oksana Goryainova, "Biomolecule"Everyone knows the "standard" of female beauty – 90-60-90.

60 seems to be a particularly "frightening" figure out of this three, namely the waist circumference. To achieve the desired 40 kilos, many girls sit on strict diets, limit themselves in food and rejoice at every kilogram that has gone. Stop, girls! Stop it! After all, a recent discovery has shown that the cells present in adipose tissue are important for immunity and protect us from infections (in particular, from Staphylococcus aureus). Interesting? Then read on!

What does our adipose tissue consist of? The bulk of the cells that make up it are adipocytes, or fat cells. Adipose tissue is widespread in the body: normally it accounts for about 15-20% of body weight in men and 20-25% in women. There are two types of adipose tissue – white and brown. Adipocytes perform many functions: accumulating fats, they play the role of energy reservoirs; provide thermal insulation and protection of organs from mechanical damage; participate in endocrine regulation.

Previously, it was suggested that adipocytes are also immunologically active cells. A recent study by scientists from the USA showed that adipocytes can protect the body from the development of dangerous skin and invasive infections caused by Staphylococcus aureus [1].

Cells vs. bacteriaIn general, several types of cells are included in the protection of the body from harmful microbes.

Since the microbe divides very quickly, it is necessary to provide an equally rapid local immune response to infection. Epithelial cells, mastocytes (mast cells) and tissue leukocytes are involved in this process. It is also important to have time to limit the spread of infection until other protective cells – neutrophils and monocytes - come to the rescue [2]. The main mechanism for limiting the growth of the pathogen is the release of antimicrobial peptides by cells. Antimicrobial peptides play a crucial role in limiting the spread of bacteria on the skin and mucous surfaces, and also prevent their spread to deep tissues where infection can develop [3].

Staphylococcus aureus, or Staphylococcus aureus, is one of the most famous and dangerous microbes. It is the main cause of most infections of human skin and soft tissues, causes focal and systemic diseases. Often, this microbe is the cause of septic shock – a deadly complication of severe infectious diseases [6].

Figure 2. An increase in the number of adipocytes during infection with staphylococcus. A – staining of the skin of mice with hematoxylin and eosin. Ctrl – control, day 1 and day 3 – demonstration of an increase in the adipocyte layer after infection with S. aureus; B – the number of adipocytes in control group mice (Ctrl) and mice infected with staphylococcus (SA). Fig. from [1].Adipocytes protect us from Staphylococcus

So what is remarkable about adipocytes as cells that help our immunity?

The researchers found that, on the one hand, already mature adipocytes present in the host body at the time of infection respond to infection. On the other hand, infection accelerates the synthesis of new adipocytes. How did they discover this?

Examining Staphylococcus aureus and infecting the skin of mice with them, scientists noticed one interesting feature – in response to infection, the subcutaneous fat layer of the mouse increased noticeably (Fig. 2A). The number of adipocytes also increased (Fig. 2B). After infection with Staphylococcus aureus, adipocytes begin to gradually increase in size, that is, the increase in adipose tissue is partially caused by hypertrophy of already mature adipocytes (Fig. 3).

Figure 3. Oil-Red-O (ORO) staining of dermal cells of the control group (Ctrl)
and cells infected with S. aureus (SA) to demonstrate lipid production. Fig. from [1].It has been shown that skin cells isolated from the area infected with the bacterium have a greater adipogenic potential (that is, adipocyte cells divide there faster than usual) compared to cells from the uninfected zone (Fig. 2B).

The number of transcription factors necessary for differentiation of preadipocytes (precursors of fat cells) into adipocytes also increases. To identify proliferating (that is, actively dividing) preadipocyte cells, scientists used bromodeoxyuridine (BDU, BrdU). BDU is able to replace thymidine in the process of DNA replication, thus embedding into new DNA. Subsequent immunohistochemical staining with antibodies to bromodeoxyuridine makes it possible to detect the included modified nucleoside, and thereby identify proliferating cells [7]. It turned out that in mice infected with staphylococcus, the number of cells with nuclei containing BrdU significantly increased. This confirmed the idea that some of the adipocytes were synthesized de novo in response to an infectious agent. It was also found that the violation of adipogenesis is accompanied by increased sensitivity to staphylococcal infection and causes systemic bacteremia (circulation of bacteria in the blood).

The secret weapon of adipocytesThe next question that interested scientists is how adipocytes can protect the body from infection?

It was found that in differentiated adipocytes, the amount of the antimicrobial peptide cathelicidin (cathelicidin antimicrobial peptide, Camp) sharply increased, while the number of other antimicrobial peptides remained the same. Similar experiments on the cell culture of human adipocytes also showed the presence of a precursor of cathelicidin in them. It also turned out to be interesting that if you sow Staphylococcus aureus on the same nutrient medium where adipocyte precursors that secreted cathelicidin previously grew, bacterial growth slows down greatly. Mice in which the growth of fat cells was specifically inhibited showed reduced resistance to staphylococcus, and this directly correlated with a decrease in their fat layer of cathelicidin.

Will excess weight help in the fight against infection?Summing up all of the above, we can say that the local increase in subcutaneous adipocytes is an important process in the body's response to skin infection.

Previously, it was known that adipocytes are capable of secreting bioactive substances – adipokines and cytokines, which mediate various post-traumatic immune reactions [8]. This study only confirms these facts. Local thickening of subcutaneous fat provides the synthesis of cathelicidin in response to infection. Also, this reaction may have an indirect benefit for immune protection, for example, to promote the formation of reactive oxygen species, radicals and nitric oxide with bactericidal activity (to induce the so-called oxidative explosion).

However, all this does not mean that it is now urgently necessary to gain weight. There are two reasons for this:

• A sharp local increase in the level of cathelicidin provides antimicrobial functions more effectively than a small increase in systemic cathelicidin as a result of obesity. For obese mice, the data turned out to be depressing – the antimicrobial peptides they produced were "defective", which made such mice more susceptible to infection [9].
• Cathelicidin is a pro–inflammatory substance, that is, it promotes the process of inflammation. That is why people suffering from obesity often have reactions of chronic inflammation in the body [8, 10].

The conclusion of the article is simple – a measure is good in everything, and you need to look for some kind of golden mean. Of course, exhausting your body with diets can not lead to anything good. Just like obesity does not contribute to overall health improvement. Eat right, take care of your health and do not worry if you have an extra fold – perhaps right now the body is helping you. Therefore, support him in this endeavor, eat some vitamin fruit and say "thank you" to your useful adipocytes.

LiteratureZhang L., Guerrero-Juarez C.F., Hata T., Bapat S.P., Ramos R., Plikus M.V., Gallo R.L. (2015).

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