Beware of Obesity during Transition to Endemic

Nearly two months have been over since Lebaran's long holiday passed without any significant upheaval. This makes many parties optimistic that the Covid-19 pandemic is transitioning to endemic. The wheels of the economy are shifting rapidly again: stations, airports, terminals, ports, hotels, shopping centers, restaurants, cafes, markets and stalls are back to full capacity.

After two years of being confined at home due to the pandemic, the long Eid holiday also means it's time to travel with family and enjoy a range of culinary delights, as if exacting revenge. It is safe to say that the prospect of a third Covid explosion has passed. There are, however, other potential dangers. Overindulgence in dining out without restraint can result in overweight or obesity, which can be fatal.

Obesity will affect blood pressure as well as glucose and body fat metabolism processes. Except for athletes, this is what will happen to obese people, defined as those with a body mass index (BMI) of greater than 30. Other people with a BMI greater than 30, such as athletes, the non-sarcopenic obesity group, and the sarcopenic obesity group, are not discussed specifically here.


Increase significantly

Obesity began to rise around the end of the twentieth century and has accelerated in the twenty-first. Obesity has been on the rise in developed countries for over 40 years. However, in many developing countries, this symptom has become more prevalent in the previous 10-20 years. According to the World Health Organization, 1.9 billion adults worldwide are overweight or obese. Excess weight can lead to a number of serious diseases, including heart, kidney, and immune system problems (cancer).

The fatter (obese) a person is, the greater the body's risk of developing disease disorders, such as hypertension and diabetes. If a person's blood pressure exceeds the normal limit (140/90 mm hg), blood flow to the kidneys will be blocked or become irregular. These disorders, if not treated promptly, can progress to severe chronic renal failure, and the patient may require dialysis or a kidney transplant. As a result, obesity can lead to diabetes and hypertension, both of which can lead to end-stage renal disease.

In Indonesia, kidney disease is the second most common disease after heart disease. According to past data from the 2013 Basic Health Research (Riskesdas), 1,499,400 Indonesians had kidney stones, and 499,800 had renal disease. This is nine-year-old information. Obesity is one of the leading causes of catastrophic diseases (including kidney failure), and the number is unquestionably much higher today.

Riskesdas 2013 also showed that 28.9% of people over the age of 18 had excessive body weight, among which 13.5% were overweight, and 15.45% were obese. In 2016, the total percentage rose to 33.5 percent, with 12.8 percent being overweight and 20.7 percent being obese. According to the 7th Report of the Indonesian Renal Registry published in 2014, 56% of chronic renal patients were under the age of 55. Chronic renal failure appears to affect predominantly those in their productive age.

Obese people are more likely to have cardiometabolic problems such hypertension (high blood pressure), diabetes mellitus, and dyslipidemia (blood lipid disorders). These three factors, individually or in combination, can have an impact on the quality of blood vessels. Obese people are more likely to suffer from strokes, heart attacks, coronary heart disease, chronic renal failure, and peripheral vascular disease as a result of their obesity.

Furthermore, high blood pressure, excessive body mass index/abdominal circumference, abnormal blood sugar, abnormal concentrations of triglycerides and HDL-cholesterol, are elements that make up the metabolic syndrome (conditions that increase the risk of hypertension, heart disease, stroke, and diabetes) or visceral adiposity syndrome (accumulation of fat tissue in the abdomen).

Additionally, uric acid levels and obstructive apnea (airway blockage during sleep) are frequently linked to metabolic syndrome. These two elements have been linked to obesity for hundreds of years. Experts have yet to decide whether or not to include these two features in the metabolic syndrome criteria.

Obesity can set off a cascade of interconnected risks in a complex way. Insulin resistance (the body's inability to convert sugar to energy) is one of them. Excess calories, sugar, fat, and salt consumption are the triggers, and it gets worse when physical activity is limited (sedentary). Technological advancements such as the advent of machinery, automobiles, computers, and gadgets have made human labor easier and have boosted the global trend toward a lifestyle with minimum physical movement.

Because less energy is expended due to a lack of exercise, the body's storage capacity increases. Major metabolic tissues (liver), muscle, and subcutaneous fat store glycogen and triglycerides. Obesity is a concern due to its harmful effects, which are caused by a combination of excessive nutrient consumption and lack of activity. Obesity can also be caused by genetic factors (heredity), which is not discussed in this article.


Become vulnerable

When one is obese, one's body condition sooner or later becomes vulnerable. One of these vulnerabilities can be seen from the low quality of blood vessels, which will result in a decrease in the quality of life. Then, why can visceral fat deposits in the abdomen be so dangerous? This visceral white fat tissue has a different metabolic activity from that of the subcutaneous tissue (tissue under the skin). The ability to respond to the antilipolytic effect of insulin in the abdominal tissue is lower than that of the subcutaneous tissue.

Lipolysis is the process of releasing fat from the tissues, while insulin functions to process food glucose into energy. The antilipolytic effect of insulin is a condition in which insulin cannot function to process glucose into energy. Because the ability to respond to the antilipolytic effect in the abdominal tissue is low, the fat and glucose stored in the abdominal tissue are difficult to convert into energy, or in other words, they are not absorbed, and accumulate over time.

On the other hand, catecholamine lipolysis is a chemical process that releases alert hormones into the bloodstream in response to stress or emotions. Studies have found that the lipolysis effect of catecholamines on abdominal tissue is higher in the tissue under the skin. That means visceral fat (in the abdominal tissue) has far more damaging properties than subcutaneous fat (under the skin).

The expansion of fat tissue in the abdomen due to consuming excessive calories tends to stimulate the recruitment of inflammatory cells, including macrophages (important cells in the immune system). These macrophages detect the accumulation of fat cells in the stomach, and this is considered a foreign substance that will disrupt the balance of the ecosystem. Therefore macrophages regard it as a threat that must be confronted and destroyed. Macrophages become active and release their weapon, namely the production of pro-inflammatory cytokines that are directly used to attack insulin. Because it is attacked, insulin is unable to carry out its function to convert fat into energy. This is why obese people are very at risk of developing insulin resistance.

In obese patients, free fatty acids will be released from the liver into the blood and into the cells (through a port called the FATP1 receptor), and change normal cellular pathways to become abnormal (called serine kinase pathway activation). Some of the products of this abnormal pathway activation are fatty acyl-CoA, a substance that damages cells' energy house called mitochondria. Then this will oxidize fats and produce reactive oxygen species which are very damaging because they are able to separate the valence of chemical bond pairs to cause oxidative stress.

In addition, other products of abnormal serine kinase pathway activation (through the so-called diacylglycerol/DAG pathway) will interfere with the sugar transport process into cells through changes in chemical reactions (modulation of IRS-1 phosphorylation and GLUT-4 function). People with obesity also experience activation of the toll-like receptor (TLR) pathway, which together increases the production of pro-inflammatory cytokines, particularly the hormone interleukin 6 (IL-6). IL-6 is what then stimulates the liver to produce inflammatory substances (C-reactive protein/CRP) which play a very important role in destroying the inner lining of blood vessel walls (endothelium), especially small blood vessels (microvascular), and leading to metabolic syndrome.

Generally, obesity may trigger insulin resistance. However, there is also obesity that does not trigger insulin resistance, for example in athletes. Generally, an athlete's body mass index is more than 30, but the circumference of the thighs and chest is wider than the circumference of the abdomen. That is, the muscles are big, but the stomach is not. But if the circumference of the abdomen also enlarges, this can lead to disease. The medical term for this is non-sarcopenic obesity.

There is a more severe category, called sarcopenic obesity (very large abdominal circumference, thinning of muscle mass, accumulation of fat in the abdomen, and very porous bone mass). These are all categories of obesity that can trigger insulin resistance. However, there are also thin people who experience insulin resistance, for example due to genetic factors (heredity) or other factors.


Obesity and risk of chronic kidney disease

Under normal and healthy conditions, kidneys are very adaptive to support the body's biological systems because they are equipped with a special autonomous system to protect themselves from various conditions. For example, when facing a disease attack. However, this self-protection does not guarantee everything. With or without kidney disease, kidney function naturally declines with age.

It is known that in young people, kidney function can reach 100 cc/minute. In old age, kidney function can decrease to 60 cc/minute, and this level is still within physiologically safe limits. The difference is, old age kidneys easily fall into a state of chronic kidney failure when faced with body disorders or extreme stress, such as obesity. Due to being depressed by obesity for a long time, kidney function decreases, which is characterized by an inflammatory process. The fatter a person is, the faster kidney function declines.

Excess weight, especially around the stomach, will cause many adverse metabolic effects that affect the kidneys. Obesity can activate the body's sympathetic nervous system, which will then release hormones that can increase sodium (salt) storage and blood pressure. Being overweight will impair the body's ability to move sugar (glucose) from the blood to cells. As a result, it is more difficult for the body to excrete excess sugar in the blood, which in turn leads to diabetes.

The explanation above shows how complex the molecular mechanisms of obesity is, and how great the risks are. So, the management and prevention of obesity in abdominal area is important so that it does not continue to become a series of serious diseases such as chronic kidney disease. Calls to maintain a healthy diet and increase body movement in daily life will be very useful to prevent disease.

The preventive health paradigm must be able to shift the curative paradigm. If this preventive health campaign can become a lifestyle, the quality of national health will increase and the burden of medical costs nationally will decrease. []


Djoko Santoso
Professor, Faculty of Medicine, Universitas Airlangga
Chairman of Health Department, Indonesian Council of Ulama, East Java


Translated from:
Mewaspadai Bahaya Obesitas di Saat Transisi Menuju Endemi
by Djoko Santoso