(46) Research on HEALTH: metabolism.

…(drums) and Researchista’s first Special Guest_Professor is Professor Dr. Ronit Shiri-Sverdlov! This is Research on HEALTH month and this month we will talk about metabolism. Let’s recall from school what metabolism is about? Metabolē means “change” in Greek and is the set of chemical transformations within the cells of living organisms (that does not only include humans, but also plants and animals). Wikipedia says that this is usually divided into two categories: catabolism – the breaking down of organic matter, and anabolism – the building up of components of cells such as proteins and nucleic acids. Usually, breaking down releases energy and building up consumes energy [Break down food – create new energy = metabolism]. This post is about on side when metabolism does not work.. called Metabolic Syndrome. I hope the post below will inspire to eat fat in a smart way!

Metabolic Syndrome: beyond simple fat accumulation

Everybody knows that consuming a healthy diet and doing physical exercise regularly are essential for keeping our health in optimal condition and our body in good shape. Although there are general guidelines that may help in defining what a healthy diet is, the term ‘healthy’ very much depends on individual needs and opinion. What is healthy can influenced by genetics, gender, age, cultural habits, nutrient availability, and socioeconomic state, amongst others. The notion that continuous malnutrition increases the risk of developing the metabolic syndrome and the associated metabolic complications is widely accepted.

Why does eating an unhealthy diet lead to detrimental effects on our organs including the liver, in some but not all individuals? Surprisingly, the effect of unhealthy diet on our body goes beyond the amount of fat. In fact, it is all about location!

Professor Dr. Ronit Shiri-Sverdlov, Maastricht University

From an evolutionary perspective, it has become clear that metabolism is a vital process, which is characterized by the efficient use of energy, as well as the ability to store excess energy for periods of food deprivation. In contrast to our ancestors, current industrialized habits are hallmarked by an excess intake of fat and sugar-enriched foods in combination with physical inactivity. This metabolic imbalance turned our former ‘survival’ state into a serious health problem, currently known as obesity, in which abnormal amounts of fat accumulates throughout the body. Nowadays, nearly one-third of the global population is overweight or obese. Lately, it has become apparent that not only adults suffer from obesity, but also children. As more and more individuals are getting obese, the metabolic syndrome is considered a major health threat.

Before taking a closer look at the liver, it is first important to understand the concept of the Metabolic Syndrome. The Metabolic Syndrome is an ‘umbrella term’ for a cluster of factors that increases the risk of developing fatty liver disease, type 2 diabetes and cardiovascular disease.

It involves a complex interplay between different organs, including the fat tissue, intestines, pancreas, brains, cardiovascular system and the liver, in which lipid homeostasis is dysregulated and metabolic inflammation is taking the lead. The liver is one of the most essential organs involved in metabolism, as it does not only regulate the storage and degradation of nutrients such as fats, carbohydrates and amino acids, but it is also involved in the detoxification of harmful compounds.

What is the exact link between the liver and the Metabolic Syndrome?

When we eat too much fat, the excess fat is transported to the liver, where it will be taken up and start to accumulate. Thus, the more fat that we eat, the more fat that accumulates inside our liver cells. Accumulation of fat in the liver is common in our society: it is present in approximately 15 percent of the general population and 90 percent of the people are currently obese. This simple accumulation of fat in the liver is still reversible and, therefore, not necessarily considered harmful. This condition, however, starts to become problematic, once the unhealthy lifestyle continue for long period of time. Accumulation of fat in the liver increases the risk of developing liver inflammation. Ultimately, liver inflammatory can lead to severe, non-reversible liver damage, including liver failure and other associated complications such as cardiovascular disease. Therefore liver inflammation is considered a major health threat.

Why does continuous intake of fatty meals can cause severe complications to our body?

When our body is in a healthy condition, specific receptors on the plasma membrane of liver ensure that the fat will be taken up and further processed. Before fat can be broken down for direct energy supply or storage, it must first enter the lysosomes. These cellular acidic organelles are small vesicles inside our cells, which contain enzymes that are capable of breaking down the fat. Once the fat has been degraded into smaller lipid particles, it can leave the lysosomes and can be either stored in the cytoplasm of the cell or can return to the blood.

When the levels of fat intake are continuously high, as observed in obese people, the fat circulates longer in the blood and consequently get oxidized. We have shown that unlike non- oxidized fat, when oxidized fat is taken up by the cells, it accumulates inside the lysosomes. The accumulation of the oxidized fat inside the lysosomes is associated with the development of liver inflammation.

What did we conclude? It is not the accumulation of fat, but rather the location by which the fat accumulates, which triggers the inflammatory response in the liver. Therefore, the actual accumulation of oxidized fat in the lysosomes could be the actual trigger for the inflammatory response. These pioneering results have shed new lights on the possible underlying mechanisms which are leading to the Metabolic Syndrome and opened new venues for the treatment and prevention of the associated clinical complications.

by Professor in Hepatic Inflammation and Metabolic Health, Dr. Ronit Shiri-Sverdlov, Maastricht University UMC+ (Maastricht University Medical Centre = Academic Hospital+Maastricht University), Genetics and Cell Biology Department.