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Obesity is the result of a complex set of genetic, evolutionary, physiological, and psychosocial factors. When treating obesity, it is important to address each of these components in order to develop efficacious and sustainable treatment plans. Lifestyle factors such as larger meal portions and sedentary lifestyles are obvious drivers of the obesity epidemic. However, a person’s weight is also influenced by complex crosstalk between gut microbiota and the immune, nervous, digestive, and endocrine systems. For these reasons, food quality, timing of meals, type of exercise, sleep and circadian patterns, and stress levels might play an important role in promoting obesity.
Insulin resistance results from impaired insulin signaling in muscle, liver, and adipose tissue, resulting in reduced whole-body glucose uptake. Insulin resistance is characterized by hyperinsulinemia that can lead to pre-diabetes, metabolic syndrome, and, ultimately, type 2 diabetes as glucose uptake in peripheral tissues fails to match glucose load. Hyperinsulinemia results in a pro-inflammatory and pro-growth state and is associated with obesity (particularly central adiposity), type 2 diabetes, cardiovascular disease and various type of cancer. A common misconception is that insulin resistance is caused by excess carbohydrate consumption, which presumes that large carbohydrate loads place a burden on the glucose-insulin axis. While reducing carbohydrate intake certainly does reduce insulin demands, low-fat, high fiber, vegetarian, and macrobiotic diets have each demonstrated dramatic reductions in insulin resistance despite a high carbohydrate intake.
The body’s circadian rhythm regulates daily patterns of behavioral and hormonal function that play a critical role in sleep and overall health. This rhythm occurs in every cell in the body and, for optimal function, needs to be synched to a central “clock” in the brain. There are several zeitgebers (rhythmically occurring phenomena that have primary control over circadian rhythm) that control the function and timing of these clocks, most notably light. In the presence of light, particularly of blue wavelengths, the hormone melanopsin is produced, inhibiting the release of melatonin. At night, in the absence of light and melanopsin, melatonin is released and contributes to sleep onset.
During the light period, particularly in the morning, larger amounts of cortisol and insulin are released. Notably, insulin secretion and insulin sensitivity are both controlled by circadian rhythms. Insulin production diminishes and remains low throughout the day unless foods requiring insulin are consumed. During the morning, we are particularly sensitive to the action of insulin. As the day progresses, we become more resistant to insulin, and during sleep we are most insulin resistant. There are likely many sources of circadian disruptors in our modern culture; for example, allowing light exposure during dark hours. Night shift workers have among the highest rates of obesity due to the presence of light at night and disordered sleep and eating rhythms.
Others circadian disruptors include frequent snacking, high-fat foods, late-night eating, and medications that alter sleep-wake patterns. These disruptions lead to altered melatonin production, a potent hormone that, when dysregulated, leads to insulin resistance, glucose insensitivity, and sleep disturbance. Interestingly, because food is also a driver of the circadian clock, intermittent fasting mitigates circadian dysfunction and, if performed appropriately, resets a dysregulated circadian clock.
Dysbiosis refers to a microbial imbalance in the small and large intestines causing an inflammatory state that is associated with impaired insulin sensitivity in muscle and adipose tissue as well as defective pancreatic islet cell function. Gut microbes vary in composition and metabolic activity depending on a variety of factors including the type of food that is ingested. Agrarian diets high in fiber and carbohydrates (fruit, legumes, and vegetables) and low in animal fat and protein have been shown to increase short chain fatty acid (sCfa) production by gut microbes. Short chain fatty acids influence appetite regulation, reduce gut inflammation, improve insulin sensitivity, and mitigate cardiovascular disease risk factors. Diets high in fat, sugar, and animal protein promote inflammation by causing gut bacteria to produce alternate compounds, branched chain fatty acids that have negative control on appetite, mood, energy levels, and even pain sensitivity.
Finally, meal timing is very important. Multiple studies have demonstrated beneficial effects of front-loading calories (consuming the majority of energy in the first half of the day) on weight loss. Along those lines, eating breakfast improves insulin sensitivity for meals consumed later in the day. Routine breakfast consumption is also associated with reduced energy intake and better regulated appetite later in the day. This suggest that we can maintain better control of energy intake, appetite, and metabolic response by front-loading calorie consumption.
Obesity occurs as a result of a complex set of genetic, environmental, and behavioral cirumstances. Insulin resistance, dysbiosis, and circadian dysfunction play major roles in the pathophysiology of obesity. Traditional long-standing caloric restriction methods tend to fail. A rational approach to lifestyle modification that includes adopting a high-fiber, whole-food based diet, front-loading calories, avoiding snacking, managing circadian rhythms, and exercising can help alleviate some of these physiologic concerns.
Source: International Journal of Disease Reversal and Prevention.
