Weight loss: causes and options

The current pharmaceutical options such as lorcaserin have clearly not been an adequate solution to problem of obesity. Extreme measures such as surgery, mitochondrial decouplers, tapeworm ingestion and illegal stimulants are not discussed.

While weight gain may be caused by medical conditions that alter water balance, commonly the weight gain is understood as accumulation of fatty tissue. Fatty tissue is caused by excess energy intake and deficit of energy expenditure (production of work, production of heat and bypass). In a biological system, such as a human, the energy intake is regulated first by availability, then by appetite and finally, by bioavailability of energy sourches such as fat, sugar, alcohol and protein. Assuming that food as an energy source is available, the energy intake is mainly regulated by appetite unless there is an overt mechanism that causes loss of energy sources, such as digestion disorders.

At the fundamental, biochemical level, there are certain biomolecules that increase or decrease appetite. Originating from the gut, Ghrelin is the primary hormone that creates sense of hunger [1] while, also originating from the gut, anorectic hormone peptide YY3-36 (PYY), cholecystokinine (CCK) and glucagon-like peptide-1 (GLP-1) reduce the appetite in response to energy intake and reduce reward to food intake in the responsible brain parts. Bile acids have an important role: these stimulate PYY and GLP-1 as well as modulate gut microbiota, which participates in appetite regulation in the one hand and energy accumulation efficiency in the other hand [2].

Fatty tissue, by default, “should” inhibit food intake by signalling via leptin and insulin that no more energy is necessary. However, due to cultural pecularities of food overconsumption in certain geographical regions especially, metabolic syndrome may be acquired. Metabolic syndrome is characterized by resistance to insulin (and probably leptin), and it is a risk factor for cardiovascular diseases and type 2 diabetes [3]. Insulin and/or leptin resistance destroys appetite control. Hence, obese people may feel hungry, probably against both their better judgement and superfluous energy reserves.

Food has hedonic reward, taste influences food intake. Food industries and art of culinary have been competing to produce as tasty foods as possible for generations. Children like sugar, for example. Considering these preferences, it is probably no wonder that corn flakes, former healthy food, has become sweeter and sweeter during course of the history [4]. In the same time, in some areas with well-entrenched healthier cuisine, such as Japan, do not experience obesity epidemic to an extent comparable to, for example, USA or Saudi Arabia. Technically, it is not even an addiction [5], and sugar preference is used in animal studies of a marker of normal enjoyment [6] despite having some traits that are sought to identify addictive substances such as dopamine and endorphin release in pleasure center of the brain [7]. While classifications may be of great academic interest, the desire to consume sweets may be comparable to desire to addictive substances and this clearly identifies it as an practical problem. It must be solved lest the situation be determined by rather hard-wired appetite and competition of capitalist food industry[8]. However, tastes can be acquired – for example when a child becomes accustomed to healthy food, that child develops a a preference for healthy food (reviewed in [1]). Taken that into account, the aquired taste of obesity-causing food is the major interventable culprit of obesity behind “junk food” eating cultures that can be identified from the world obesity maps readily available with the help of online search engines. Indeed, genetics plays a part, about 20% according to a huge population based genome-wide population study [9]. It is known that the americans of japanese origin have above-average rates of diabetes in USA [10]. Japan has experienced infiltration of western-like foods such as instant noodles to everyday diet of the japanese, and now the prevalence of type II diabetes or glucose resistance in Japan is 13.5% [11]. However, in Japan people tend to walk instead of driving, eat different foods and do not accept obesity as ‘normal’, and rate of their obesity is much lower than everywhere else in the world. Hence, the nutritional solution is exercise combined with diet of Japan 1975 (it was the maximally healthy one according to analysis) [12]. While the debate about the superiority of low-fat or low-carb diet is continuing in mainstream media, in the scientific literature the debater is more or less over. Low-carb diet and Mediterranean diet are clearly superior to low-fat approach [13], far superior.

Pharmaceutical solutions are at best secondary, unclear at worst. Surgery is the last resort. There are certain other add-on interventions provided by cosmetic industry but these, too, are supplementary. The primary interventions are exercise and diet. The supremacy of (A) traditional Japanese diet, (B) low-carb diet (see also ketogenic diet) and (C) traditional Mediterranean diet are established and most likely, must be part of the solution.

[1] https://pubmed.ncbi.nlm.nih.gov/28229538/
[2] https://pubmed.ncbi.nlm.nih.gov/28356427/
[3] https://pubmed.ncbi.nlm.nih.gov/24582089/
[4] https://www.diabetes.co.uk/blog/2015/03/sugar-in-cereal-who-are-the-worst-offenders/
[5] https://pubmed.ncbi.nlm.nih.gov/27372453/
[6] https://rndb.clps.brown.edu/task/sucrose-preference-test/
[7] https://pubmed.ncbi.nlm.nih.gov/20648910/
[8] https://pubmed.ncbi.nlm.nih.gov/23719144/
[9] https://pubmed.ncbi.nlm.nih.gov/25673413/