Etiology of obesity

Obesity results from a positive energy balance maintained over a prolonged period of time. The mechanisms underlying this positive energy balance are numerous, complex, and to a large extent beyond a person's control. Obesogenic factors such as stress, alterations in sleep patterns, sedentary jobs, increased screen time, and endocrine disruptors are among a few. Genetic and epigenetic susceptibility, aging, menopause, medications, and hypoglycemia also can contribute to obesity (Obesity Medical Association, 2021).

Lifestyle 

Physical, economic, social, and political environments impact lifestyle choices. The current human condition is driving unhealthy choices and overconsumption. (Vandevijvere S, Swinburn B 2014). Overall adherence to the US Dietary Guidelines is low: most Americans do not follow a healthy eating pattern. Together with physical inactivity, eating an energy-rich, nutrient-poor diet predisposes one to many chronic diseases,
Covid 19 negatively impacted obesity lockdown imposed changes in lifestyle behaviors with considerable short-term, and long-term health and nutritional consequences increased cardiometabolic risk, consistently linked to worsened prognosis (Antwi et al., 2021).

Genetic influences

• High precision genetic diagnostic tools have identified numerous genes influencing the phenotypes associated with the early onset of severe obesity ( Thaker,2017).
• Familial studies show that BMI is highly correlated with parental obesity. Children whose both parents are obese, have higher risk of being obese (Albuquerque, 2017).
• The obesity epidemic has to consider arising from both genetics and the environment.

Genetic causes of obesity can be broadly classified into:

• Monogenic causes: those caused by a single gene mutation, primarily located in the leptin-melanocortin pathway
• Syndromic obesity is severe obesity associated with phenotypes such as neurodevelopmental abnormalities and other organ system malformations.
• Polygenic obesity is caused by the cumulative contribution of many genes whose effect is amplified in a ‘weight gain promoting’ environment..

Genetic factors and the environmental factors that influence the expression of these genes play a large role in the development of obesity in children, adolescents and young adults. (Thaker, 2017).

Environmental influences

The increased prevalence of obesity in recent decades has been driven largely by environmental factors such as increased food consumption, highly sweetened beverages, reduced physical activity, sedentary habits, etc. rather than biological ones.

The cost of food has been found to influence the purchasing and consumption decisions of individuals and families.“ Healthier foods cost nearly twice as much as unhealthier foods per serving on average (mean healthy-to-unhealthy ratio = 1.97 [SD 0.14]). A larger healthy-to-unhealthy price ratio was associated with lower odds of a high-quality diet (OR = 0.76 per SD increase in the ratio, 95% CI = [0.64–0.9])” (Kern et al., 2017) So if a healthy diet is more expensive than an unhealthy diet the impact on a family with a low socioeconomic

Neurobiology

Hormones secreted by the gastrointestinal (GI) tract, adipose tissue, and pancreas regulate energy homeostasis by stimulating the central nervous system to produce the sensations of appetite or satiety. Appetite regulating hormones cross the blood-brain barrier to act on receptors in the hypothalamus or by stimulating the hypothalamus via afferent vagal nerve impulses generated by nerve endings on or near the GI tract. 

The body defends its highest fat mass, i.e., diet restriction and weight loss increase ghrelin-induced hunger and the desire to eat while also suppressing the satiety effect of the hormone leptin, which can create a vicious cycle. Some of the hormones known to regulate appetite include ghrelin, leptin, insulin, and cholecystokinin (Yeung & Tadi, 2021).

Ghrelin is a hormone produced primarily in the fundus of the stomach, that increases appetite, and also plays a role in increasing body weight. Diet-induced weight loss is associated with increased levels of ghrelin (Sumithran et al., 2011).

Leptin is an anorexigenic (hunger suppressing) peptide produced in the adipose tissue, gut and pancreas. It is often referred to as the “satiety hormone” or the “starvation hormone".  Leptin’s primary target is the hypothalamus. It also has many other functions related to fertility, immunity and brain function.  Calorie restriction causes a leptin decrease that is disproportional to weight loss and energy expenditure. Sumithran et al. (2011) found at ten weeks, with a weight loss of 14%, leptin decreased by 65%. 

Insulin regulates several aspects of the development and function of adipose tissue and stimulates the differentiation program of adipocytes.  Two types of intracellular insulin receptors (INSR) have been identified; INSR-A and INSR-B. INSR-A, is mainly linked to adipocyte proliferation (hyperplasia), and INSR-B, is more associated with excess lipid storage (hypertrophy) and metabolic pathologies common to obesity (Cignarrelli 2019).

Cholecystokinin (CCK) is a hormone synthesized by neuroendocrine cells scattered throughout the mucosa in the proximal two-thirds of the small bowel. It is released in response to lipid and protein content of a meal. CCK slows gastric emptying and activates CCK receptors on the afferent vagal nerve that subsequently affect central nervous system nuclei involved in appetite regulation (Miller 2021).

 

A number of theories have been offered to explain how modern nutritional bounty and environmental factors work together to predispose humans toward overweight and obesity. The following are a few examples:

• Homeostatic theories help describe some feeding behaviors when energy input and output are relatively balanced
  • Glucostatic theory posits that a drop in glucose metabolism by neurons in the hypothalamus stimulates hunger and feeding behavior. Conversely, increased glucose metabolism by cells in the hypothalamus generates feelings of satiety and suppresses the desire for food. The Glucostatic theory may predict self reported hunger and satiety but not how long someone will stay full (Krishnan,et al. 2019).  Chaput and Trembray (2009) found that Glycemic reduction associated with post-gastric bypass, very low energy diets, carbohydrate-restricted diets and weight loss beyond 10% of body weight, destabilizes energy homeostasis inducing psychobiological vulnerability that favors weight regain.
  • The lipostatic theory assert that adipose hormones and metabolites modulate hunger and that both lipostatic and glucostatic homeostasis are regulated by insulin.
• Non-homeostatic theories describe dysregulated feeding behaviors affected by
  • Learned/Hedonistic factors of preference, i.e., pleasure and disgust
  • Social and economic factors, e.g. externally influenced feeding cycles, externally influenced nutrient input
  • Psychologic disorders
  • Genetic predisposition
• Integrative theories that describe the affect of gut-brain interaction on dietary decision-making (Plassman 2021).

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