When talking about body fat regulation we always have to adhere to the basic laws of thermodynamics. We know that increases in body fat mass happens when energy intake is higher than energy expenditure, and that we have to either decrease energy intake, increase energy expenditure, or both in order to lose weight. This basic fact has led many to believe that weight loss is all about eating less and/or exercising more. However, what we also have to account for is that the body is not a passive vehicle that just comes along for the ride. We already know that carbohydrates, fats, and proteins have a different thermic effect in the body and thereby differentially influence energy expenditure. We also know that food choices and diet composition have an impact on hormone levels, inflammatory processes, gut microbiota, reward centers in the brain, etc. and can thereby influence appetite, energy intake, and energy expenditure.
Food reward hypothesis
Some calorie-dense and highly palatable foods, such as pastries, pizza, hamburgers, and other common products in the western diet, are generally considered more fattening than simple, whole foods such as meat, vegetables, and fruits. But why is it so? If body fat regulation is all about energy in vs. energy out, it shouldn’t really matter what we eat as long as we don’t consume more calories than we need to sustain bodyweight. However, since dietary choices can impact both energy intake and energy expenditure through several mechanisms, we know that simply talking about calories is too simplistic.
Many processed westernized foods are hyper-rewarding in the sense that they contain a potent combination of sugar, salt, starch, fat, glutamate, and/or other food ingredients that in combination can overwhelm the reward center in our brain (1,2). Food manufacturers know how to use these hard-wired mechanisms to their advantage and hire scientists to design products that we essentially become addicted to (3). From an evolutionary perspective, there’s no doubt that these foods are novel introductions in the human diet. Hunter-gatherer and some traditional, non-westernized populations eat primarily simple, whole foods, and the absence of westernized food in these populations can help explain the extremely low obesity rates in these cultures.
This idea, that highly rewarding processed foods causes us to overeat and are the major driver of the obesity epidemic has been labelled the “food reward hypothesis.” At this point there are several studies supporting this hypothesis, and many obesity researchers consider food reward to be the primary player in the obesity epidemic. Essentially, the food reward hypothesis suggests that the reason we eat more calories than we need to sustain bodyweight is because these highly palatable, processed foods cause us to overeat (4).
Another important player that has emerged over the last decade is the human microbiome. Just like the food reward theory, this hypothesis is based on the idea that there are some factors about the modern obesogenic environment that cause us to store more fat. This goes back to the original premise, the gene-environment mismatch we’re now facing in the modern industrialized world is the fundamental cause of the obesity epidemic. Also, just like the food reward hypothesis, the microbiome hypothesis focuses on the western dietary pattern and the impact highly processed foods have on our health. However, here the focus is primarily on the changes these diets promote in our gut, not the impact they have on our brain. Also, the microbiome hypothesis stretches far beyond just diet.
It’s well established that a refined western diet promotes changes in the bacterial communities in the gut, which contributes to weight gain (5). However, we know that many aspects of our lifestyle other than diet impact the human microbiome. Antibiotics are routinely used in livestock to fatten animals up, and studies in humans have also linked antibiotic exposure in childhood to fatness later in life (6,7) . Some researchers have even proposed that the obesity epidemic in the U.S. could be partially driven by the use of antibiotics in livestock, which reach humans through food (8). Also, caesarean section and bottle feeding in infancy have been linked to being overweight later in life (9,10). Other factors, such as microbial exposures, microbial ecosystems in the home, and microbes inherited from mum, probably also play a role, but these things are harder to measure in scientific studies.
How can gut microbes affect body weight regulation?
How is it that these critters in our gastrointestinal tract are able to influence body fat regulation? Most of the early studies on the gut microbiome and obesity focused on the role gut bacteria play in energy harvesting. Essentially, it was believed that the “obese” gut microbiota extracted more energy from food and that this elevated energy acquisition was the reason for increased fat storage. However, what we’re now learning is that although this energy extraction probably does play a role, the small difference in energy acquisition can only account for some of the difference between the lean and obese microbiota. Many more theories have appeared, but a common theme is inflammation (11,12,13).
The gut microbiota controls the absorption of luminal content from the gut into systemic circulation by regulating intestinal barrier function, and this mechanism could help explain why gut bacteria play such an important role in immunity and inflammatory processes in the body. Microbes in the large intestine ferment indigestible food components (to the human host) and produce short-chain fatty acids. These fatty acids are the primary fuel for the colonocytes lining the large intestine and have been shown to regulate the differentiation and expansion of several types of T cell in the gut (14). This effect on immunological homeostasis is believed to be one of the key reasons gut microbes play such an important role in human health.
We know that obesity increases the risk of colon cancer, type-2 diabetes, cardiovascular disease, and a wide range of other inflammatory disorders. We also know that these conditions often go hand in hand with alterations in the gut microbiota and that these perturbations play an important role in the pathogenesis of these disorders. This suggests that one of the reasons obese people have a higher risk of many diseases is because they have an altered gut microbiota, which often harbor more proinflammatory microbes.
However, it’s not just microbes in the large intestine that have a significant impact on our health. The small intestine also harbors complex microbial communities, and one of the most interesting hypotheses related to the gut microbiome and obesity revolves around these critters. Ian Spreadbury (PhD), at the Gastrointestinal Diseases Research Unit, Queen’s University, Kingston, Ontario, Canada, has written a paper where he hypothesizes that refined carbohydrates change the balance of microbes that live in the small intestine and that these alterations promote fat gain (15).