POLYUNSATURATED FATTY ACIDS

The composition of the cell membrane reflects the result of two factors related to the individual: diet and metabolism. Just by looking at this composition, it becomes clear that special attention should be paid to the choice of fats in foods and also to assessing their transformation in the body, especially keeping in mind the indispensable role played by polyunsaturated fatty acids (PUFAs), omega-6 and omega-3, as structural and functional elements of the cell membrane.

The omega-3 PUFA family, whose best-known molecules are EPA and DHA, are long-chain fatty acids that participate in membrane fluidity, especially of the membrane of cells in the nervous system and retina (for more on omega-3 DHA) and are precursors of molecules with signalling activity, the most important of which is anti-inflammatory.

PRO-INFLAMMATORY OMEGA-6?

In signaling activity, on the other hand, omega-6 PUFAs, unlike omega-3s, have a “negative reputation, namely being pro-inflammatory.” Arachidonic acid is the best known of the omega-6 polyunsaturates, producing signal molecules to direct our body’s reactivity in an inflammatory direction.

Omega-6 fats are considered “inflammatory” par excellence, but this meaning is incorrect and this “bad reputation” is challenged precisely by scientific knowledge and evidence, perhaps not known to all, but widely shared by those in the field:

• 1- First of all, it should be remembered that among omega-6 PUFAs there is dihomo-gamma-linolenic acid DGLA, which is one of the molecules formed in the “enzymatic cascade”: linoleic acid (found in foods) → gamma-linolenic acid → DGLA → arachidonic acid (more on this at www.lipinutragen.it/en/dgla-at-the-crossroads-of-pro-and-anti-inflammatory-processes). As soon as DGLA is formed-rather than turning all into arachidonic acid-it is more rapidly transformed into series 1 prostaglandins, important signal molecules for anti-inflammatory processes and immune activation;
• A second point is that inflammation, generated by the transformation of arachidonic into its signal molecules, series 2 prostaglandins, does not arise as a harmful process in itself, but is our body’s physiological response to attack and ward off a problem. However, in order to have an optimal inflammatory process, it must evolve over time, indeed in a short time it must be able to extinguish itself (i.e., “resolve”), and to achieve this it must give way to other signal molecules (either from omega-3 or from DGLA) that intervene immediately afterwards with anti-inflammatory activity; the balance also applies reciprocally, i.e., even the presence of omega-3 cannot be in excess of omega-6, precisely so as not to cancel out its reactive and defensive signals.

The omega-6 and omega-3 families, in addition to sharing the characteristic of essentiality, that is, having to introduce their precursors necessarily through the diet, because the human body is unable to self-produce them, also share the “enzymatic machinery” to carry out the metabolic transformations that “cascade” from the precursors to the components of the two families.

This means that starting with the diet, foods containing omega-6 and omega-3 must be introduced equivalently, without excesses of either family, because this ensures the presence of all PUFA molecules for structural and functional membrane balance, including pro- and anti-inflammatory balancing (2).

GAMMA-LINOLENIC FATTY ACID, OMEGA-6

Dihomo-gamma-linolenic acid (DGLA)

In the omega-6 family we find gamma-linolenic acid (GLA), a semi-essential fatty acid, which is derived from its essential precursor, linoleic acid (LA).

From GLA, in turn, dihomo-gamma-linolenic acid (DGLA) is formed enzymatically.

The biological activities of GLA and DGLA are well documented in the scientific literature and involve anti-inflammatory and regulatory properties:

• • DGLA competes with arachidonic acid for COX and LOX enzymes (which convert into prostaglandins and other signal molecules of the inflammatory process);
  • DGLA is a precursor of prostaglandin series-1, with anti-inflammatory, anti-aggregatory and vase-dilatory activity;
  • GLA and DGLA, transformed into their oxygenated metabolites, have various effects, such as increasing cyclic AMP levels and enhancing mitochondrial activity, as well as interacting with various receptors, supporting the activities of immune cells, mucosal cells (intestinal, gastric, and genital apparatus) and smooth muscle, and other metabolic activities. Finally, by acting as regulators of apoptosis and vascularization, they are very important in the management of the tumour process.
    Additional positive effects are clinically found such as increased defences, improvement of gastro-intestinal issues, reduction of menstrual discomfort, and hydration and elasticity of the skin.

It should be emphasized that in all these evaluations, there is always the caveat of assessing the presence of natural and non-natural fatty acids, such as saturated fats and trans fats, in the same formulation that contains PUFA fatty acids. In fact, if you want to get to specific effect supported by PUFAs, you have to be sure to have them as main components, while saturated and trans fats constitute undesirable components that interfere with the main biological activity.

LiGLA: THE FIRST GLA-BASED SUPPLEMENT IN EMULSION

The enzymatic transformations of linoleic acid into GLA and then into DGLA are not always fast and efficient; in some cases they may not perform well, such as in certain pathological conditions (hypertension, arthritis, diabetes, and psoriasis) or related to bad habits or nutrition (alcohol use, stress, smoking, diets deficient in vitamins and minerals).

Intake from food sources (or supplements) turns out to be a valuable solution to deficits or deficiencies. Please note that fatty acid deficiencies or deficiencies can nowadays be analyzed, thanks to membrane lipidomic analysis (analysis processed in our Laboratory with the only accredited method with robotic procedure), so that symptoms simply due to essential fatty acid deficiency are not mistaken as pathology.

NUTRITION SOURCES OF GLA

There are no naturally available sources of DGLA, while there are some (not many) natural sources of GLA such as borage, evening primrose and blackcurrant oils (with varying concentrations of GLA), which can be used in nutraceutical products.

Lipinutragen has studied LiGLA, a supplement in liquid emulsion form based on borage oil with 20 percent GLA, along with antioxidants, alpha-lipoic acid, and sunflower lecithin.

THE DISTINCTIVE FEATURES OF LiGLA

Borage seed oil selected as raw material has the highest concentration of GLA on the market, i.e., 20 percent, and has a very low saturated fatty acid content and no trans fatty acids.

The formulation in the presence of lecithin allows GLA to be absorbed more easily (higher bioavailability for microparticles), distributing itself in an effective and protected manner, thanks to the presence of the antioxidants (Vitamin C, Vitamin E and lipoic acid).

After absorption and biodistribution in the cells of various tissues, GLA fatty acid enters the omega-6 family metabolism and cascade to be transformed into DGLA. Polyunsaturated fatty acids, including DGLA, are then used to biosynthesize phospholipids and, as such, are incorporated into cell membranes. And right here we read the final balance between omega-6 and omega-3 with the presence of DGLA being very important for the fine regulation of pro- and anti-inflammatory signaling in a natural way.

Bibliography:

1. Membrana cellulare e lipidomica. Carla Ferreri e Chryssostomos Chatgilialoglu. 2014, CNR Edizioni
2. Harayama et Riezman. Understanding the Diversity of Membrane Lipid Composition. Rev Mol. Cell Biol. 19:281-296, 2018.
3. Kapoor R, et al. Gamma Linolenic Acid: An anti-inflammatory omega-6 fatty acid (Review) Curr Pharm Biotech 7:531-34, 2006.
4. Burdge G, et al. Alpha linolenic metabolism in adult humans. Eur J Lipid Sci Tech 107:426-39, 205, 2005.
5. Das UN. Essential fatty acids and their metabolites could function as endogenous HMG-CoA reductase and ACE enzyme inhibitors, anti-arrhythmic, anti-hypertensive, anti-atherosclerotic, anti-inflammatory, cytoprotective, and cardioprotective molecules. Lipids Health Dis. 2008 Oct 15;7:37. 
6. Wang X, Lin H, Gu Y. Multiple roles of dihomo-γ-linolenic acid against proliferation diseases. Lipids Health Dis. 2012 Feb 14;11:25.

EFSA CLAIM:

EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of health claims related to gamma-linolenic acid (GLA) … pursuant to Article 13(1) of Regulation (EC) No 1924/2006. EFSA Journal 2011; 9(4):2059. [27 pp.]. doi:10.2903/j.efsa.2011.2059.

CLINICAL TRIALS:

• Wu D, et al. Effect of dietary supplementation with black currant seed oil on the immune response of healthy elderly subjects. Am J Clin Nutr 70: 536-543, 1999
• Zurier RB, et al. Gamma-linolenic acid treatment of rheumatoid arthritis. A randomized, placebo-controlled trial. Arthritis Rheum39:1808-17, 1996.
• Keen H, et al. Treatment of diabetic neuropathy with gamma-linolenic acid. The gamma-Linolenic Acid Multicenter Trial Group. Diabetes Care 16:8-15, 1993.
• Physicians’ Desk Reference for Nutritional Supplements, 1st Edition, ISBN 1-56363-364-7, p. 173.
• Chilton-Lopez T, et al. Metabolism of GLA in human neutrophils. J Immunol 156:2941-47, 1996.
• Johnson M, et al. Dietary supplementation with GLA alters fatty acid content and eicosanoid production in healthy humans. J Nutr 127:1435-44, 1997.
• Ziboh VA, et al. Dose-response effects of dietary GLA-enriched oils on human polymorphonuclear-neutrophil biosynthesis of leukotriene B4. Am J Clin Nutr 55:39-45, 1992.
• Barham JB, et al. Addition of eicosapentaenoic acid to gamma-linolenic acid-supplemented diets prevents serum arachidonic acid accumulation in humans. J Nutr 130:1925-31, 2000.
• Laidlaw M, et al. Effects of supplementation with fish oil-derived n-3 fatty acids and gamma-linolenic acid on circulating plasma lipid profiles in women. Am J Clin Nutr 77:37-42, 2003.
• Wang C, et al. n-3 Fatty acids from fish or fish-oil supplements, but not alpha-linolenic acid, benefit cardiovascular disease outcomes in primary- and secondary-prevention studies: a systematic review. Am J of Clin Nutr 84:5-17, 2006.

Article by the Lipinutragen Editorial Team
The information reported should in no way replace the direct relationship between health professional and patient.

Photo: 123RF Archivio Fotografico: 162388984 : ©denisfilm | 121975769 : ©vainillaychile 

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Weight gain

“We are what we eat” so says Ludwig Feuerbach and even before him Hippocrates; the awareness of a connection between our being and our food has very distant roots, although in a constantly moving and always too busy society, such as the one in which we live, it is clear that the strength of this connection is being lost and is not part of our priorities.

The hustle and bustle of our modern lives, but also the spread of “mass-produced” products, is leading us to neglect the qualitative choice of daily food in favor of poor-quality management, which also becomes impulsive and often influenced by the fashions of the moment. This inevitably leads to a steady increase in cases of overweight and obesity.

The scientific consensus debates extensively on the issue of obesity, which is being called the epidemic of the 21st century, and for the past few years has also been focusing attention on the overweight condition, representing it as the transition time between the conditions of normal weight and obesity.

An overweight person is defined as having a Body Mass Index (BMI) between 25 and 30. This weight condition is already identified as a disorder/dysfunction, although not as serious as obesity; it can also be found associated with changes at the psychological level (such as no longer accepting one’s body) and/or pathological conditions (such as joint problems).

Overweight arises when there is an energy imbalance (energy introduced with food is greater than that consumed) and is caused mainly by unhealthy behaviors, particularly unhealthy eating habits and sedentariness.

Overweight in Italy

A recent article published in the National Epidemiological Bulletin of the Istituto Superiore di Sanità (ISS) provides a clear cross-section of the distribution of overweight in Italy while also explaining the correlations that exist between this disorder and factors such as territory, gender and level of education.

First of all, the study shows an increase in the percentages of overweight individuals from 2008 to the present, and that between the ages of 18-69 there is a prevalence of overweight of 40% for men and 25% for women considering the resident population in Italy (Tab.1 of the study) and that the geographical areas with the highest incidence are those of Central and Southern Italy.

Age, moreover, is a very important correlating factor with overweight; in fact, it can be seen that as age increases, excess weight tends to increase. This is until the age of 75, an age when due to disease or physiological wasting, weight tends to decline.

Another important factor that the study highlights is the correlation of excess weight with educational level: in fact, the higher the educational qualification, the lower the percentage of people with excess weight. This inverse correlation is very pronounced when obesity is taken into account while it is almost zero when it comes to overweight (Fig.1 of the study).

From this study, therefore, it is clear that the segment of people who are overweight are those who work and that economic or educational conditions do not affect them as much as one might think. This confirms that it is indeed lifestyle that has the greatest impact on moderate weight gain.¹

With this in mind and with a view to prevention, the Ministry of Labor has issued a series of directives to encourage a better lifestyle and healthier diet in the workplace, with ad hoc guidelines for each sector; to date, however, these indications still have little grip on the entire Italian workforce.²

Lipids and overweight

Overweight is clearly due to fat accumulation, and this is plaguing a large part of the population in Italy.

In common perception all fats cause weight accumulation, so everything fat is to be fought without distinction. Instead, science has made it clear, now very well, that it all depends on the quality of lipids if weight change occurs, showing that healthy normal-weight, overweight and obese subjects have very different fat composition (lipid composition, in technical terms).

To simplify, overweight subjects have a higher proportion of fatty acids from the monounsaturated family than normal-weight subjects and, unlike obese subjects, have a lower proportion of fatty acids from the omega-6 family, particularly arachidonic acid.

Overweight molecular view

How should this arrangement be read? Still keeping to a simple description, it can be summarized that, when you are overweight, you are in an “intermediate phase,” where the body is certainly accumulating fats in the adipose tissue, but it is also possible that in the body their displacement (mobilization of fats) to organs (e.g., muscles, during some physical activity) where they can be useful takes place. The fat accumulation in that case is predominantly monounsaturated fats, and only then does it not yet become “a problem.”

Everything changes, however, as the diet of those who like to take in more food than they need becomes enriched with saturated fats. In this case, the adipose tissue of those who are going overweight is transformed, accumulating saturated fats instead of monounsaturated fats. This brings about a progressive inflammatory state and a change in the function of the adipose tissue, which will gradually move-and even may facilitate-the overweight state toward the condition of obesity.

In conclusion, if fats are accumulating, it is better to know which fats they are. With an appropriate lipidomic investigation, one can understand the quality of fats in the overweight condition and also what transformation the accumulation is leading to in the body. This will indicate, therefore, how to bring the metabolism, with appropriate individualized nutritional strategies, to turn around.

Bibliography:

1. Masocco M, Minardi V, Contoli B, Minelli G, Manno V, Cobellis L, Greco D. Sovrappeso e obesità nella popolazione adulta in Italia: trend temporali, differenze socio-anagrafiche e regionali con focus sulla Regione Campania. Boll Epidemiol Naz 2023;4(1):1-8. DOI: https://doi.org/10.53225/BEN_059
2. Linee di indirizzo per la prevenzione e il contrasto del sovrappeso e dell’obesità. Ministero della Salute. https://www.salute.gov.it/imgs/C_17_pubblicazioni_3256_allegato.pdf

To know more:

• Correlation sugars & fats:
  www.lipinutragen.it/en/sugars-and-fats-connection/
• Childhood obesity:
  www.lipinutragen.it/en/childhood-obesity/

Articolo a cura del Gruppo redazionale di Lipinutragen

Le informazioni riportate non devono in alcun modo sostituire il rapporto diretto tra professionista della salute e paziente.

Photo: 123RF Archivio Fotografico: 168526018 : ©whitebearstudio1 | 112065444 : ©jetsam86

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Fatty acids, our beloved lipids

The scientific knowledge of lipids is one of the oldest. Indeed, it has always been recognized how essential fats are to life, as fundamental constituents of cells.

Lipids are made by the human body itself, but also taken in through the diet.

Fatty acid categories

Depending its molecular structure, 3 categories of fatty acids are distinguished:

• Saturated (SFA)
• Monounsaturated (MUFA)
• Polyunsaturated (PUFA)

The first two, saturated and monounsaturated, are produced by the body by biosynthesis and also taken in through diet. The polyunsaturates, distinguished in turn into the omega-3 and omega-6 families, cannot all be produced biosynthetically because there are no enzymes present to convert monounsaturates to polyunsaturates. So, through the diet we take in the first polyunsaturates (precursors of the omega-6 and omega-3 families) and then the body transforms them into other polyunsaturated (so-called long-chain) fatty acids, completing the whole lipid kit needed by cells.

In this article, we will focus our attention on the saturated fat.

Saturated fats, to fear?

Saturated Fatty Acids (SFAs) are the most talked category of lipids; demonized and banned for several years because they were associated a health risk, they are now no longer labelled as harmful, although the scientific discussion is still going on. However, scientists agree that their consumption, meaning the consumption of foods containing them, should be moderated.

What does moderate consumption mean? Since our bodies can produce saturated fatty acids in the necessary and sufficient amounts for metabolic needs, as mentioned above, the consensus is that saturated fat intake can be kept around 15-22 g/day. Recall that fats are often valued in the form of calories, so the convention applies to determine how many calories should be introduced per day (e.g. 2000 calories/day) and of these how much should come from fats of the various types (e.g. saturated fat 220 calories).

In lipidomics, fats are not only calories, but it is necessary to consider not only the quantity of fats but their quality according to their biological role. Thus, the rule of not overdoing a prevailing quality of one type of fat applies even more, especially when – as in the case of saturated fats – they can be produced by the body independently as needed.

NOTE: Remember that saturated fats can also arise indirectly from the activation of their production in the body due to a boost from excessive carbohydrate consumption.

Monitoring dietary saturated fat intake can be a good purpose to practice in daily choices. The food label in this control comes to our aid.

Cell membrane, fatty acids balance

With many years of experience in our Lipidomics Laboratory, making use of cell membrane lipidomics analysis as a tool to verify the quality and quantity of fatty acids present in the body (by means of an ISO 17025 accredited robotic procedure at Lipinutragen, unique in the world), we can state that excessive consumption of saturated fats leads to a condition of imbalance that triggers, in turn, an inflammatory type response at the level of various tissues.

The optimal status is represented by maintaining a balance between the three categories of fatty acids described above, which is consequently reflected in the proper composition of the cell membrane, the lipid layer necessary to give form and function to every single cell in the human organism.

The composition of the cell membrane depends on dietary lifestyle and metabolism. Therefore, special attention must be paid to the choice of fats introduced through diet and, if necessary, through supplementation.

Article by the editorial team of Lipinutragen
The information reported must in no way replace the direct relationship between the health professional and the patient.

Photo: 123RF Archivio Fotografico: 185032521 : ©tanatpon13p | 206211818 : ©nsit0108

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Scientific knowledge on LipiMagazine

The LipiMagazine blog was started about 9 years ago to disseminate the scientific knowledge that belongs to our field, and to emphasize its great applicability in daily life.

In particular, the applicability of membrane lipidomics is given by its direct and indirect correlation to epigenetic factors such as lifestyle, diet, health/wellness condition, etc.

Sugars and inflammatory potential

Carbohydrates, simple and complex (the latter, polymers of simple sugars), are macronutrients, basic nutrients along with proteins and fats (lipids).

When we consume sugars, the body begins to digest them, for passage through the digestive tract.

Simple sugars, such as glucose, sucrose (table sugar) or fructose (sugar found in fruit) are absorbed more quickly because they are already in the usable form, unlike complex carbohydrates (polymers of simple sugars) for which more “digestive effort” is required.

Carbohydrates taken in through nutrition, give a metabolic response with insulin production, and it is clear that an excess of this intake over-stimulates the producing organ, the pancreas.

Gradually, with an excess of sugar utilization, at all ages, a greater “insensitivity” to the insulin stimulus can be created in the cells, which is called “insulin resistance,” and this phenomenon triggers an inflammatory response from the cells.

Sugars and saturated fatty acids

In addition, when sugars are in excess, another process is begun: the stimulus for the production of saturated fatty acids (SFAs). Recall that saturated fats are the type of fats that our body synthesizes (“produces”) and there is no need to take in.

With saturated fats increasing, either by direct intake or indirect formation from carbohydrates, cellular structures called membranes in particular are affected, in which areas of increased rigidity are created (SFA fats accumulate), thus affecting their organization and function. This molecular phenomenon leads to an imbalanced condition, which in turn triggers an inflammatory-type response.

From a prevention perspective, to avoid triggering the gear of inflammation, action can be taken on several fronts, starting with the food choices we are called upon to make on a daily basis (e.g., controlling dietary intake of saturated fats, and also indirectly excessive intake of carbohydrates).

!!! Beware of products called “light” and 0% fat. In almost all cases the reduction in fat has been replaced by more sugar, proving to be anything but an advantage.

Sugar” themed library releases:

The topic of “sugars” has been covered extensively in several articles, which for ease of reference we list below:

• Sugar varieties: the focus on NATURAL AND ARTIFICIAL SWEETENERS.
  https://www.lipinutragen.it/en/sweeteners
• Sugary drinks and the effect on our body:
  https://www.lipinutragen.it/en/sweetened-drinks/
• 7 useful tips for a sugar-free life: https://www.lipinutragen.it/en/what-life-would-be-without-sugar/
• Glycemic index and factors influencing its elevation:
  https://www.lipinutragen.it/en/impact-glycemic-index/
• Overweight in children and the 7 dietary mistakes:
  https://www.lipinutragen.it/en/childhood-obesity/

• ARTICLE FOR SPECIALISTS* on diabetes prevention and the role of fatty acids:
  https://www.lipinutragen.it/en/fatty-acids-and-diabetes-prevention/

*Scientific and technical language is used in this article.

Sugar-free or sugar-substitute nutrilipidomic recipes:

• Fruit salad with Nutra Pick nectar (sugar-free):
  https://www.lipinutragen.it/en/nutra-pick-fruit-salad/
• Everything you need to know about honey and a recipe for a lemon-scented sauce:
  https://www.lipinutragen.it/en/honey-nutritional-content/

Article by the editorial team of Lipinutragen
The information reported must in no way replace the direct relationship between the health professional and the patient.

Photo: 123RF Archivio Fotografico: 149585480 : ©niceideas

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Enzyme reactions and fatty acids

The liver is the main organ deputed to the synthesis of fatty acids (lipogenesis); it has the “vocation” of initiating the cascade of enzymatic reactions provided for lipogenesis. Without fats, no cell can live, and for this reason, the liver is an indispensable organ.

Lipogenesis involves three consecutive stages (see figure):

• the ex-novo synthesis of palmitic acid, a saturated fatty acid (16 carbon atoms);
• the two-unit elongation reaction of the palmitic acid structure, transformed into stearic acid (18 carbon atoms). Palmitic acid and stearic acid are the two main saturated fatty acids in our cells, and the cell membrane of the hepatocyte (as shown in the table in the article www.lipinutragen.it/en/liver-and-its-cells-hepatocytes/) also has an amount of up to 40-45% of its total components;
• the subsequent transformation, which is very important and necessary precisely for hepatic metabolism, of stearic acid into oleic acid (monounsaturated fatty acid with 18 carbon atoms) by insertion of a double bond (in technical terms, enzymatic desaturase; see figure shown as delta-9 desaturase or SCD-1).

It is highlighted that saturated fats, although necessary for the formation of cells and the cell membrane, must necessarily be transformed into monounsaturated fats to allow the two components (saturated and monounsaturated) to mix and ensure adequate flow and permeability properties, which are necessary for vital functions.

Hepatic metabolism and membrane composition

In hepatic metabolism, transformation takes on particular significance, as seen in the figure taken from a major review in 2009 [1]. In fact, the ability to “desaturate” has an impact on adaptation and metabolic flexibility of the liver cell.

If the hepatocyte contains sufficient proportions of monounsaturates, the cell membrane remains functional for metabolism, allows adaptation to all demands, and if the fat load increases, lipid accumulation evolves into a condition of steatosis, but without destructive effects.

In the case of impediment of saturated fat transformation, on the other hand, there is an increase in the saturated component over the monounsaturated component, with structural change of the hepatocyte and consequent cellular damage, corresponding to a condition of steatohepatitis. In this condition, there will also be an imbalance in favor of inflammatory-type signaling, which increases the destructive rather than regenerative potential of this very important cell.

Lipidomic analysis and liver status interpretation

To know how the liver is functioning, whether it is in metabolic homeostasis or whether it has developed metabolic or inflammatory issues, health experts have at their disposal an analytical tool that accurately reports the composition of the hepatocyte: lipidomic analysis of the mature red blood cell (performed in our Lipidomics Laboratory with exclusive robotic equipment, according to ISO 17025 accredited method).

The molecular information present in the outcome of membrane lipidomic analysis is the complementary aspect to biochemical-clinical (for GOT-GPT-ALT transaminase values, C-reactive protein, etc.) and diagnostic (such as ultrasonography) examinations to assist therapeutic and/or nutritional strategies.

Only by supporting the balance of the lipid pool can the regenerative potential of the hepatocyte be fully expressed, sustaining metabolic demands at all ages and occasions (as described in the article www.lipinutragen.it/en/liver-and-its-cells-hepatocytes/).

Essential bibliography:

[1] Alkhouri,N.; Dixon, L.J.; Feldstein, A.E. Lipotoxicity in Nonalcoholic Fatty Liver Disease: Not All Lipids Are Created Equal Expert Rev Gastroenterol Hepatol. 2009, 3, 445–451
[2] Ferreri, C.; Chatgilialoglu, C. Membrane Lipidomics for Personalised Health, page 39, Wiley, 2015

Read more in LipiMagazine:

• NON-ALCOHOLIC HEPATIC STEATOSIS: www.lipinutragen.it/en/liver-organ-not-to-be-overloaded/
• THE SCIENTIFIC VALIDITY OF MEMBRANE LIPIDOMICS: www.lipinutragen.it/en/lipidomic-membrane-analysis/

Article edited by the Lipinutragen Editorial Group in collaboration with Dr. Carla Ferreri, CNR Director in Bologna and Scientific Director of Lipinutragen

The information reported should in no way replace the direct relationship between health professional and patient.

Photo: 123RF Archivio Fotografico: 178359670 : ©mol4un

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Molecular balance to maintain good liver function

The liver is made up of cells, the hepatocytes, which are 80 percent of its total mass. These cells are veritable factories for the formation and transformation of molecules, whose mitochondria work by producing metabolites and energy, supplying, among other things, high amounts of albumin, coagulation factors and other proteins that are found in the circulation. Liver products also include bile salts, which come from cholesterol metabolism.

A look at cell activity ^[1]

Another role played admirably by hepatocytes is detoxification, which is the transformation through a veritable enzymatic arsenal (collectively called P450 enzymes) of toxic molecules that arrive from throughout the body through the venous (portal vein) bloodstream. This valuable work allows toxic products to be converted into products that can no longer do harm and can be eliminated from the body through excretion pathways.  This transformation also takes place to eliminate drugs.

In this continuous “metabolic” work, the liver may become fatigued, but it is important to note that this tissue has higher regenerative capacity than other tissues, i.e., it is able to fully regenerate cell mass and function after being affected by different types of problems. It can be said that under normal conditions and without alteration of the natural balance, the liver has a “slow” turnover, between cells that have reached the end of their life and cells that divide to generate new cells (only 1-2% of all cells divide). The time can be estimated in months with an average life span of 180 days.

If it is subjected to a series of events of an infectious, traumatic, or even metabolic or vascular nature, the liver can accelerate the formation of new cells; for example, interestingly, after resection of part of this organ, it is able to rebuild its initial mass. This expresses the enormous potential for liver regeneration, which does not have to be altered and can respond naturally by repairing damage.

Liver fatigue and impact on metabolism

The liver, in its fundamental role as a “molecule factory,” can also go into fatigue with issues that impact overall metabolism. In this case, the most predominant origin of liver problems lies in dysregulation of fat metabolism.

When it comes to lipids, it is clear that further investigation with cell membrane lipidomic analysis can allow us to pinpoint exactly where the balance of hepatic functioning is broken, giving substantial help in framing the liver condition and also suggesting rebalancing strategies.

Recall that membrane lipidomic analysis is performed on the mature red blood cell (average life span 120 days), a cell representative of tissues throughout the body, but in particular a faithful mirror of the composition of the hepatocyte, to which it is virtually equal as a distribution of saturated, monounsaturated and polyunsaturated fats (tab from [2] work in bibliography).

Liver cell growth and replication underlie the resolution of most liver damage; it is important to understand how to succeed in maintaining the regenerative potential of this organ over time by supporting the formation of a balanced lipid pool, a prerequisite for the formation of fully functioning cell membranes.

Bibliography:

[1] Stanger, B. Z. Annu. Rev. Physiol. 2015, 77:179–200
[2] Ferreri, C.; Chatgilialoglu, C. Membrane Lipidomics for Personalised Health, page 39, Wiley, 2015

Article edited by the Lipinutragen Editorial Group in collaboration with Dr. Carla Ferreri, CNR Director in Bologna and Scientific Director of Lipinutragen

The information reported should in no way replace the direct relationship between health professional and patient.

Photo: 123RF Archivio Fotografico: 197311168 : ©zodyak53

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CELL STRESS: WHERE TO FIND IT?

Our life is in a state of continuous dynamic equilibrium. On a daily basis, our body is subjected to stresses of various kinds, stressors that undermine the physiological balance.

At the cell level, a stressor can:

• trigger an adaptive response >> stimulus to achieve a new balance with adaptive benefits
• create reversible damage >> stimulus to “fix” the condition that caused the stress
• create irreversible damage and lead to cell death (apoptosis).

Conditions such as intense sports, psychophysical stress, infections, exposure to pollutants, sun or other sources of radiation, and smoking, combined with unregulated lifestyles and poor dietary intake of antioxidants, can lead the cell to increase free radical production. Conditions in which antioxidant defences are depleted and the stressed condition may not be compensated for.

OXIDATIVE STRESS OR RADICAL STRESS: are the same?

The term oxidative stress is often used to refer to the formation of free radicals.

Oxidative stress and radical stress are two different molecular processes.

During the stress phenomenon, reactive oxygen species (ROS) of two types are formed in the cell:

1) oxidizing molecules, such as hydrogen peroxide

2) free radicals, such as the “famous” hydroxyl radicals (OH•). Free radicals are “transient,” i.e., unstable, species whose half-life is much shorter and reactivity quite different from oxidizing species.

Therefore, in the former case the term “oxidative stress” is used, while in the latter case it is more appropriate to speak of “radical stress.”

Recognizing whether one is dealing with oxidative stress or radical stress is important when one has to choose the ANTI-STRESS strategy, but this distinction can only be made by a specialist who will identify the most suitable ANTI-OXIDANT or ANTI-RADICAL synergy, including through membrane lipidomic analysis.

Consequently, “DO-IT-YOURSELF” in stress is definitely the worst choice, because resorting to antioxidants without knowing the molecular process may be useless or even deleterious.

ANTIOXIDANT-THEMED INSIGHTS:

Some in-depth readings on the topic of antioxidants and dietary supplementation:

• Before purchasing a supplement, it is important to know that…
  www.lipinutragen.it/en/food-supplements/
• Antioxidant action supplementation:
  www.lipinutragen.it/en/antioxidant-integration/
• Cell reinforcement with antioxidants:
  www.lipinutragen.it/en/strengthening-the-body/
• Easy homemade ice-cream recipe with natural antioxidant action ingredient:
  www.lipinutragen.it/en/antioxidant-ice-cream/

Article edited by the Lipinutragen Editorial Group.

The information reported should in no way replace the direct relationship between health professional and patient.

Photo: 123RF Archivio Fotografico: 196865541 : ©zannagap | 79736145 : ©fancytapis

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Aging: from the cell the secret to living longer

Over the past 20 years, a tremendous amount of knowledge about aging has developed that has clarified how this natural process is due to a combination of factors ranging from genetics to the environment, including lifestyle and diet, as well as the degree of exposure to a variety of conditions that lead to the development of diseases [1].

Aging, oxidation and regeneration

Science is clearly indicating that favourable aging is achieved by proper prevention throughout life, by monitoring at the level of the individual the functioning of the organism, through parameters ranging from macroscopic ones-such as weight and abdominal fat accumulation-to those referring to the life of cells, i.e., the smallest vital part of our organism. The natural phenomenon of aging is related to the increase in oxidative reactions and damage to the molecules that are the cell’s heritage, with oxidative and inflammatory responses then leading to cell death. Not everyone knows that there are cells of different ages and with different “life expectancies” within the same organism, so aging and cell death are completely natural phenomena that must occur within the times of the average life expectancy for different cell types, reported in the Table.

The cell is an important site for assessing how we are aging, because while it is true that all cells have a life span, i.e., they age and die, as many new cells are formed to make sure that tissues are reciprocated and are always functioning. In each time frame as cells age, new ones are formed following the cell cycle shown in the figure, ranging from G1 -> S -> G2. During the cycle, considerable effort is made to duplicate the “kit” of molecules and form two daughter cells (in a process called mitosis). This cycle ensures that there are always cells available for the functions of systems, organs and tissues [2].

At this point we put the cycle into operation, as if it were an “assembly line,” taking as an example the epithelial cell (which forms the “carpet” of our epithelia, i.e., skin) with a life span of 18-20 days. If the necessary molecular make-up cannot be fully formed, the process will slow down. Cells would not have replacement available, and more tired and aged cells will linger more in the tissue. Here is where the skin will accumulate many more defects, creating problems of normal functioning: lack of hydration and oxygenation, high sensitivity, loss of support and elasticity.

Cell replacement must occur precisely in synergy with “cellular senescence” (aging of the cell) first theorized in 1961 for fibroblasts (connective cells) [3]. In place of heavily oxidized cells come new cells, regenerating tissue.

The membrane and its balance for longevity

In the late 1990s, Prof. Antony Hulbert published a compendium of the lifespan of animal species, including humankind, and reported a striking graph, on the years of life as a function of the fat composition of the cell membrane (shown is the composition of skeletal muscles of mammals and birds) [4]. Specifically, taking up the concept of oxidation assessed in aging, the graph shows the polyunsaturated fat content or peroxidation index of the membrane as a function of age. It is clearly seen that the more polyunsaturated fats the membrane contains, the shorter the lifespan in the animal.

From this observation, the theory of the cell membrane as a “pacemaker” for aging was born, and two important pieces of information were obtained:

• The amount of polyunsaturated fats in the cell membrane must be optimal, i.e., no deficiencies should be found, but neither should excesses be found, because in the latter case the peroxidation index increases, and this correlates with reduced life expectancy. An analysis of the membrane lipidome provides precise information about the content of fat molecules, and whether there is an optimal complement to meet life expectancy and turnover times.

• From the composition of the membrane lipidome, the secret to optimal turnover and promoting cell life can be studied. It is precisely on reading the membrane to delineate human profiles that Lipinutragen has been developing its R&D for some time. In 2008, the cell membrane of the mature erythrocyte of the Cilento population, one of the areas with the highest presence of centenarians, was studied, discovering a peculiar characteristic of the descendants of the long-lived [5]: compared with other fellow citizens not descended from longevans, and with the population of other geographical areas, the offspring of centenarians have the erythrocyte membrane richer in monounsaturated fatty acids, particularly palmitoleic acid, a specific molecule that activates cellular anti-inflammatory signals and for lipid metabolism, and participates in membrane fluidity without increasing oxidations.

Analysis of the membrane lipidome of the mature red blood cell is the only analysis that allows us to examine the individual status and, if deficiencies or excesses of lipid molecules are found, to implement a rebalancing strategy, aiming to protect the cellular make-up, promoting proper turnover and regeneration, two important processes involved in longevity and good health.

Bibliography:

[1] Collection: Aging, longevity and age-related diseases. Nature Aging al sito: https://www.nature.com/collections/dbagdcagdb
[2] C. Ferreri, C. Chatgilialoglu. Membrane Lipidomics for Personalized Health, 2015, pag. 64, Wiley and Sons.
[3] Hayflick L. The limited in nitro lifetime of human diploid cell strains. Exp Cell Res. 1965, 37, 614–636.
[4] Hulbert A. J. Explaining longevity of different animals: is membrane fatty acid composition the missing link? Age 2008, 30, 89–97.
[5] Puca A.A., Novelli V., Viviani C., Andrew P., Somalvico F., Cirillo N.A., Chatgilialoglu C., Ferreri C. Lipid profile of erythrocyte membranes as possible biomarker of longevity. Rejuven. Res. 2008, 11, 63–72.

Other articles related to the longevity theme:

Lifestyle medicine: www.lipinutragen.it/en/way-to-longevity/

Cell replacement: www.lipinutragen.it/en/membrane-lipid-therapy/

Article by the Editorial Group of Lipinutragen

The information given should in no way replace the direct relationship between health professional and patient.

Photo: 123RF Archivio Fotografico: 169729456 : ©zven0 | 114983921 : ©designua

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