|Posted on December 11, 2020 at 1:55 PM|
The “chemical obesogen” hypothesis conjectures that synthetic, environmental contaminants are contributing to the global epidemic of obesity. In fact, intentional food additives (e.g., artificial sweeteners and colors, emulsifiers) and unintentional compounds (e.g., bisphenol A, pesticides) are largely unstudied in regard to their effects on overall metabolic homeostasis. With that said, many of these contaminants have been found to dysregulate endocrine function, insulin signaling, and/or adipocyte function. Although momentum for the chemical obesogen hypothesis is growing, supportive, evidence-based research is lacking. In order to identify noxious synthetic compounds in the environment out of the thousands of chemicals that are currently in use, tools and models from toxicology should be adopted (e.g., functional high throughput screening methods, zebrafish-based assays). Finally, mechanistic insight into obesogen-induced effects will be helpful in elucidating their role in the obesity epidemic as well as preventing and reversing their effects.
Keywords: obesity, BPA, bisphenol A, food additives, preservatives, pesticides, plastics, pollutants, contaminants
Since the industrial revolution, the goals of food technology have predominately been maximizing palatability, optimizing process efficiency, increasing shelf life, reducing cost, and improving food safety (free from harmful viruses, bacteria, and fungi). As such, over 4,000 novel ingredients have entered the food supply, some intentionally (such as preservatives) and some inadvertently (such as bisphenol A, BPA), and there are 1,500 new compounds that enter the market every year . While food processing techniques are also constantly being optimized to minimize toxic compounds and toxicants such as lead, melamine, and aflatoxin, other “non-toxic” additives are not thoroughly tested for their chronic, additive, and/or cumulative effects on human physiology.
Obesity and related chronic disorders are increasing at alarming rates and it is estimated that 86% of Americans will be overweight by 2030 . This trend continues despite increases in awareness, nutritional and behavioral research, the amount of diet foods available, and even gym memberships . Unfortunately, the etiology of obesity and diabetes in regard to biochemical mechanisms is still largely not understood. Treatment and prevention of obesity hinges on our ability to 1) characterize the biochemical pathways that promote obesity, 2) identify what changes in our environment are promoting obesity, and 3) avoid and reverse the effects of the offensive agents and practices. It is crucial that clinicians understand and communicate that most novel food ingredients have not been evaluated for metabolic safety. In this review, we outline what agents have been identified that may be contributing to obesity, describe current methods being used to identify offensive compounds, and identify critical gaps in our methods and body of knowledge.
The importance of identifying agents that contribute to obesity
There is an abundance of research related to obesity etiology and prevention in regard to decreasing caloric intake and increasing energy expenditure. However, “non-traditional” risk factors are under increased scrutiny for their contributions to the obesity epidemic: emotional stress, sleep deprivation, disruption of normal circadian rhythm, composition of the gut microbiome, oxidative stress, medications such as antidepressants and oral contraceptives, average home temperature, and environmental toxicants [24••,36•,55]. Agents in our food supply have immense potential to affect metabolism due to continuous exposure and potential interactions among multiple compounds. A recently hypothesized factor contributing to the obesity epidemic is our exposure to obesogens, chemicals in our environment that can disrupt metabolism and lead to accumulation of excess fat mass (coined by Grün and Blumberg in 2006 ). It is critical that we identify these obesogens in our food supply in order to facilitate obesity prevention and treatment .
Unfortunately, many of the obesogenic compounds in our food supply were added deliberately to enhance production instead of being added to enhance nutrition. For example, pesticides are added to ward off insects during farming; BPA is a strong, clear plastic that has ideal properties for making bottles and coating cans; and mono- and diglycerides are added to emulsify the fat and water in foods to achieve a favorable texture. Simple exclusion of these compounds may not be possible until alternatives are developed, but then these novel compounds must be tested. Like pharmaceuticals, thorough testing is time-consuming and expensive.
Obesogen identification and characterization is in its infancy, and much of the scientific evidence supporting the relationship between synthetic compounds and the obesity epidemic is currently weak. Strong, evidence-based scientific support is derived from randomized, controlled trials, ideally cross-over design, that comprise four steps: 1) addition of the compound of interest, 2) observation of an effect, 3) removal of the compound of interest, and 4) disappearance of the effect. However, the bulk of evidence relating environmental contaminants and obesity is derived from epidemiological studies which are correlational by nature. While correlations are important, they are limited in that conclusions about causal relationships are impossible. Well-designed animal studies provide strong evidence within the animal model, but must be confirmed in humans. Cell studies are important for deriving mechanisms that may link certain compounds to obesity, yet provide only weak evidence for the global phenomenon (the obesity epidemic). Thus, we currently do not have any strong evidence that any contaminant, food additive, or ingredient that is “generally recognized as safe” (GRAS) causes obesity, which is essential for making confident recommendations and changes in public policy.
It is important to note that in evaluating foods for their contribution to obesity, we may identify ingredients that prevent obesity. For example, some hydrocolloids including guar gum and β-glucan may be able to increase satiety and reduce caloric intake with their bulking properties . Also, anthocyanins (potent color compounds from grapes, purple corn, blueberries, and other plants) may reduce oxidative stress, prevent obesity, and help control diabetes in cell culture, animal models, and humans . Again, not all compounds in a class are equal; for example, although the hydrocolloid guar gum may prevent obesity (mentioned above), another hydrocolloid called carrageenan, found commonly in chocolate milk and ice cream, may contribute to insulin resistance in mice .
What in our food is making us fat?
There are many aspects of the average Western diet that may promote obesity. The macronutrient ratio (fat:carbohydrate:protein), the characteristics of the fat (e.g., diets rich in palmitic acid vs. eicosapentaenoic acid), the characteristics of the carbohydrates (refined vs. whole grain carbohydrates) [2,59], and form of the protein  are major concerns and reviewed elsewhere [2,59-63]. In addition, advances in food processing have facilitated consumption of high caloric food that is low in other nutrients (e.g., edible oils, refined grains)  as well as increased the glycemic load of common meals . Increased consumption of nutrient-poor added fat, added sugar, added salt, and refined grains may also underlie obesity and co-morbidities in ways that extend beyond energy balance . Baillie-Hamilton announced a well-received hypothesis in 2002 highlighting the potential for environmental compounds in our food to contribute to the obesity epidemic . While the relationship between obesity and food structure is reviewed elsewhere [59-63], herein, we will focus on potential obesogens and obesity-promoting food additives in our foods supply (Table 1)......... https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4101898/