SLT Explanation of Anorexia

Biological Explanations of Obesity

Obesity — defined as a body mass index (BMI) ≥ 30 — is a major and growing public health challenge, associated with substantially elevated risk of type 2 diabetes, cardiovascular disease, certain cancers, and reduced life expectancy. Biological explanations propose that genetic predisposition, neurobiological regulation, and evolutionary mismatches between ancestral physiology and modern food environments all contribute to the development and maintenance of obesity.

Genetic Factors

Twin studies provide compelling evidence for genetic contributions to obesity. Stunkard et al. (1986) studied twins raised apart — finding MZ concordance for BMI of approximately 74%, compared with approximately 32% for DZ twins, even when the twins had been raised in different environments from birth. This is amongst the highest heritability estimates for a complex trait — heritability of BMI is estimated at 40–75% across studies. Adoptee studies (Stunkard et al., 1986) also found a strong correlation between adoptees' BMI and their biological parents' BMI, but not their adoptive parents' BMI — further separating genetic from environmental transmission.

Candidate genes: the FTO gene (fat mass and obesity-associated gene) is the most strongly replicated common genetic variant associated with obesity — individuals with two risk alleles of FTO have approximately 1.67 times the odds of obesity compared with those with no risk alleles (Frayling et al., 2007). FTO appears to regulate energy expenditure and appetite. Other risk genes include MC4R (melanocortin 4 receptor — regulates appetite in the hypothalamus) and LEPR (leptin receptor — variants associated with leptin resistance). Like most complex traits, obesity is polygenic — hundreds of common genetic variants each contribute small effects.

The thrifty gene hypothesis (Neel, 1962) proposes that genes promoting efficient energy storage were adaptive in ancestral environments characterised by feast-or-famine food availability. Individuals who could store energy efficiently (as fat) during times of plenty survived better during periods of scarcity. In modern food-abundant environments, these same 'thrifty genes' promote excessive fat storage, producing obesity. This evolutionary mismatch account is consistent with the high prevalence of obesity in populations with recent history of famine (e.g. Pacific Islander populations) compared with populations with historically stable food supplies.

Set Point Theory: Biological Defence of Body Weight Low High Body Weight Set Point Zone (defended range) Weight BELOW set point ↑ Ghrelin ↓ Leptin ↓ Metabolic rate ↑ Hunger → body drives weight back up Weight ABOVE set point ↓ Ghrelin ↑ Leptin ↑ Metabolic rate ↓ Hunger ← body drives weight back down Counter-regulatory response Counter-regulatory response Set point can shift upward over time with chronic overeating — explaining why recovered weight after dieting is often higher than the original set point

Set Point Theory

Keesey and Corbett (1984) proposed that body weight is regulated around a biologically determined set point — a defended weight range that the body actively maintains through homeostatic counter-regulatory mechanisms. When weight falls below the set point (e.g. through dieting), the body responds by:

  • Increasing ghrelin levels (increasing hunger)
  • Decreasing leptin levels (reducing satiety signalling)
  • Reducing metabolic rate (adaptive thermogenesis) to conserve energy
  • Increasing the hedonic value of high-calorie foods

These combined responses powerfully resist weight loss and drive weight back towards the set point, explaining the difficulty of maintaining dietary weight loss. The set point is not entirely fixed — it can shift upward with chronic overeating (potentially through changes in hypothalamic leptin sensitivity), which may explain why obesity, once established, is difficult to reverse.

Leptin Resistance and Hypothalamic Dysfunction

In typical physiology, leptin produced by adipose tissue signals the hypothalamus to reduce appetite and increase metabolic rate. In obesity, a common pattern is leptin resistance: circulating leptin levels are high (because there is substantial adipose tissue producing it), but the hypothalamus fails to respond normally — meaning satiety signals are not generated despite elevated leptin. Causes of leptin resistance include: hypothalamic inflammation (associated with high-fat diets); reduced leptin transport across the blood-brain barrier; and downregulation of leptin receptors. The result is a vicious cycle: high leptin → resistance → inadequate satiety signalling → continued overconsumption → more adipose tissue → even higher leptin.

 Key Takeaways

  • Twin studies (Stunkard et al., 1986): MZ concordance ~74% even in twins raised apart; heritability of BMI 40–75%. Strong genetic contribution established by adoption studies.
  • FTO gene (Frayling et al., 2007): most replicated common variant — two risk alleles → 1.67× odds of obesity. MC4R, LEPR also implicated. Obesity is polygenic.
  • Thrifty gene hypothesis (Neel, 1962): genes promoting efficient energy storage were adaptive during feast-or-famine in the EEA — now maladaptive in food-abundant modern environments.
  • Set point theory (Keesey and Corbett, 1984): body defends a weight range through counter-regulation — ↑ ghrelin, ↓ leptin, ↓ metabolic rate when weight falls. Explains difficulty of maintaining weight loss.
  • Leptin resistance: in obesity, high leptin levels fail to suppress appetite — hypothalamus does not respond normally. Causes: hypothalamic inflammation, reduced receptor sensitivity, impaired blood-brain barrier transport.
  • Set point can drift upward with chronic overeating — potentially via leptin resistance and hypothalamic inflammation — helping explain why established obesity is difficult to reverse.