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Combating obesity with science

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Published the 11/10/2021


Obesity is the fifth leading cause of death worldwide, and fourth leading cause of death in Europe. To lower our body mass index and to raise our self-esteem, we need to know the molecular aspects of weight loss! This article complements the previous article called: Obesity: a giant problem.


Food degradation

Cells require a constant supply of energy to generate and maintain the biological order that keeps them alive. This energy is derived from the chemical bond energy in food molecules, which thereby serve as fuel for cells. The intermediary molecules that the body uses to store energy is called Adenosine triphosphate, or ATP for short. Excess energy is also stored in chemical bonds, mainly those of fatty acids, the main components of our fat tissue.


There are three distinct types of food that we can digest, and a vast majority of our energy supply comes from one of them: proteins, lipids or fats, and polysaccharides or sugars. All of them must be broken down into smaller molecules before our cells can use them, either as a source of energy or as building blocks for other molecules. The breakdown processes must act on food taken in from outside, but not on the macromolecules inside our own cells.


Stage 1 of the enzymatic food degradation is therefore digestion, which occurs either in our intestine outside cells, or in a specialized organelle within cells, the lysosome. In either case, the large molecules comprised of multiple units (polymers) in food are broken down during digestion intoindividual subunits (monomers)—proteins into amino acids, polysaccharides into sugars, and fats into fatty acids and glycerol—through the action of enzymes. After digestion, those small monomers enter the the cell where they get disassembled further by oxidation.




Figure 1: breakdown of large macromolecules into simple subunits.




In stage 2, a chain reaction called glycolysis converts each sugar molecule into two smaller molecules of pyruvate and subsequently into Acetyl-CoA, producing ATP. Amino acids and fatty acids skip this step and directly undergo a process called the citric acid cycle, which is the third and final stage in the energy production process and occurs only in mitochondria.





Figure 2: schematic view of glycolysis and the citric acid cycle. The whole process can be simplified by approximating the pathways as such: amino acids get broken down and mostly used as building blocks, unless there is a shortage of sugars and fatty acids. Sugars undergo glycolysis, produce pyruvate and subsequently Acetil-CoA, which enters the citric acid cycle, and produces the most amount of energy in oxidative phosphorilation, in the form of ATP. Fatty acids get directly broken down into Acetyl-CoA, and continue on the same pathway as sugars.


As our diet changes to contain more of one of those three types of food, our body adapts to be more efficient in breaking it down. This happens in stage 1 with the help of various enzymes, and takes the body approximately three weeks to fully adapt to the change. A common example of miracle diets is to cut carbohydrates (or carbs, sugars) and shift the diet towards mostly protein-based nutrition. The body, which had a majority of its derivates be carbohydrates until now, and had the enzymatic profile appropriate for that diet, suddenly finds itself without its primary energy source. Regardless of the amount of other energy sources, it is not able to produce sufficient energy from the up until recently auxiliary sources, due to lack of appropriate enzymes. This results in weight loss coupled with digestion problems and extreme overload of liver, which tries to compensate for the missing enzymes. After the aforementioned three weeks, the body gradually adapts to the new regime, and the yo-yo effect occurs. Unless, we do it all again by changing our diet back to „normal“.
Apart from cell and organ starvation, this method carries a significant risk of liver and kidney damage, or even their failure.

Understanding the energy cycle can be of great help in combating obesity as it prevents


Value of food

Nutritive value of food is often disregarded while talking about diets. In contrast to the energetic value, which gives us the estimate energy our body can produce from certain food and is measured in calories or joules, nutritive value is the amount of vitamins, minerals and other helpful chemical entities found inside, which help the body function properly and execute all of its functions such as hormone secretion, digestion and general homeostasis. If the energetic value is the gas to our engine, the nutritive value is the oil, the brake fluid, coolant and others.

WHO reports more malnutrition every year in countries where obesity is most prevalent. A sentence contradictory to itself several decades ago has become a rising concern, especially for children under five years of age. We are used to the notion that malnutrition equals low body weight and insufficient food intake. While that might still be true in some underdeveloped countries, more recent studies place the prevalence of malnutrition in those countries lower than in some developed countries. It is not uncommon to find under- or malnutrition coexisting with obesity within the same country, the same city, or even the same household.

All of this sums up a disturbing notion of modern cuisine: people, but especially children, are exposed to high-fat, high-sugar, high-salt, energy-dense, and micronutrient-poor foods, which tend to be lower in cost but also lower in nutrient quality. These dietary patterns, in coupled with lower levels of physical activity, result in sharp increases in childhood obesity while under-nutrition problems remain unsolved.



Exercise

A simple way to loose weight is to exercise, a practice known from the dawn of time. Physical effort of any kind escalates our metabolic needs, and our fat reserves are used up to combat the rising energy needs during exercising. Yet, entire fields of study are dedicated to the notion of exercise and weight loss, not only in scientific terms, but also in form of cosmetics, gyms, supplements, devices, diet plans, advisors and others, in a far greater quantity. Why is it so hard to loose weight (for most people, at least), when there is a simple formula for doing so: if input > output , we gain weight. If input<output , we loose weight. This is related to the energetic value of food: if we consume more calories than we spend, we gain weight, and if we spend more than we take in, we loose weight. The reason there is a limit to the amount of fat a body can store is the ever-increasing energy demand for maintaining that weight. Although body fat is relatively inert, its cells still need a constant maintenance in terms of nutritive and energetic value.

Several factors contribute to the difficulty of the task, but the major problem lies with the two hormones, leptin and serotonin. Serotonin awards every decision that prolongs and secures our homeostasis, that is, our body's well-being, and loosing weight and depleting energy reserves is certainly not on that list. So, as the pangs of hunger claw deeper and the energy reserves deplete, lack of serotonin associated with food intake increases. Leptin, on the other hand, while initially positive in terms of weight stabilization, is linked to serotonin's function, and will succumb to its relentless nagging for that 1 a.m. ice cream. You giving in to the temptation of a chocolate cake is not for your lack of perseverance, but for the lack of serotonin. Several studies linked personal happiness with lower body weight and healthier lifestyle.

Other factors include the prevalence and abundance of high-fat, high-sugar, high-salt and energy-dense food served at every fast food restaurant and stall. People are generally lazy as a function of energy conservation, and if something is available now, they will get it now. Prevalence and availability of energy-dense food leads to prevalence of obese people. Related to this is is the already mentioned lack of nutrient. Needing nutrients, we feel the urge to eat. But if the food is nutrient deficient, obesity is imminent. Lack of exercise is, however, the biggest obstacle in any attempt to loose weight.



Diets as a way of life

Having discussed the negative dietary concepts, let's now focus on the positive ones and try to ease the burden of weight loss.
First and foremost, some sacrifices will have to be made. Change comes when the aspects of future are more desirable than those of the present, and if we want for the future us to be healthier, leaner and feel better, we need to adjust the present in a sustainable way. To help with the process, we need to view diets as a permanent state, and not just a phase or an ordeal to overcome. The sooner we understand this, the easier it becomes.

It also takes time. As discussed before, three weeks is the minimum amount of time our body needs to adjust to change. We also need to keep in mind that this change comes in small, sustainable steps, and we should adjust the diet to be just as sustainable. Slow and steady wins the race.

We can manipulate our input-output equation on both ends to achieve the desired input<output state: we can reduce the calorie intake into our body, and increase the output values by exercising. The best results are achieved by doing both.

Reducing the input of calories doesn't mean eating less and being hungry: it means eating energy-poor foods rather than energy-rich ones. A device such as a calories counter could be of great help in this regard.
The same rule applies for exercising: slow and steady wins the race, and exercising less in more frequent intervals will always be preferable to an occasional, extremely hard sweat.

Controlling the input and output of energy can be a daunting goal, but one worth pursuing. Not only does loosing weight prevent diabetes, cancer, osteoarthritis, and cardiovascular diseases, but it also raises self-esteem, and lifts a big burden made of fat from our backs, in both a literal and proverbial sense!





References:

1. A meta-analysis of the past 25 years of weight loss research using diet, exercise or diet plus exercise intervention. Miller, W., Koceja, D. & Hamilton, E. Int J Obes 21, 941–947 (1997). https://doi.org/10.1038/sj.ijo.0800499

2. Cost and cost-effectiveness of obesity treatment: A mini review. Chu N-F, Chu W.Health Prim Car, 2019., vol. 3, 1-3. doi: 10.15761/HPC.1000163

3. Diet, physical activity or both for prevention or delay of type 2 diabetes mellitus and its associated complications in people at increased risk of developing type 2 diabetes mellitus. B. Hemmingsen, G. Gimenez‐Perez, D. Mauricio, M. Roqué i Figuls, M-I. Metzendorf, B. Richter. Cochrane Database of Systematic Reviews 2017, Issue 12. Art. No.: CD003054. DOI: 10.1002/14651858.CD003054.pub4. Accessed 21 October 2021.

4. Dynamic Adaptation of Nutrient Utilization in Humans. El Bacha, T., Luz, M. & Da Poian, A. Nature Education 3(9):8

5. Long-term weight loss after diet and exercise: a systematic review. Curioni, C., Lourenço, P. Int J Obes 29, 1168–1174 (2005). https://doi.org/10.1038/sj.ijo.0803015

6. Molecular Biology of the Cell. 4th edition. Alberts B, Johnson A, Lewis J, et al. New York: Garland Science; 2002.

7. Nutrient Utilization in Humans: Metabolism Pathways. Da Poian, A. T., El-Bacha, T. & Luz, M. R.M.P. (2010). Nature Education 3(9):11

8. The Hormonal Control of Food Intake, Coll A. P., Farooqi I. S., O'Rahilly S. Cell. 2007 Apr 20; 129(2): 251–262.doi: 10.1016/j.cell.2007.04.001

9. The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review. Klok M. D., Jakobsdottir S., Drent M. L. Obes Rev. 2007 Jan;8(1):21-34. PMID: 17212793. DOI: 10.1111/j.1467-789X.2006.00270.x

10. https://ourworldindata.org/obesity#8-of-global-deaths-are-attributed-to-obesity

11. who.int/news-room/fact-sheets/detail/obesity-and-overweight

12. https://www.metabolics.com/blog/how-does-the-body-produce-energy

13. https://www.fda.gov/food/new-nutrition-facts-label/how-understand-and-use-nutrition-facts-label





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