Obesity Flashcards
The mu-opioid receptor (MOR), kappa-opioid receptor (KOR), and delta-opioid receptors (DOR) are localized in brain regions mediating food intake and reward
Opioid antagonists work by blocking opioid receptors in the brain, reducing the pleasure and reward associated with eating, particularly high-fat or sugary foods.
This helps in reducing cravings, overeating, and improving control over eating behaviors.
The combination of naltrexone with bupropion (as in the drug Contrave) has shown effectiveness in managing weight loss by targeting both the opioid and dopamine systems involved in appetite and reward.
While effective for many, side effects and individual variability should be considered when using these medications for obesity management.
Classification of overweight and obesity (adults)
Healthy weight 18.5–24.9
Overweight 25–29.9
Obesity I 30–34.9
Obesity II 35–39.9
Obesity III 40ormore
What are the progressive interventions with obesity?
General advice on healthy weight and lifestyle
Diet and physical activity
Diet and physical activity; consider drugs
Diet and physical activity; consider drugs; consider surgery
What causes obesity?
Body weight and body fat content are typically stable over time
= energy homeostasis or balance
The brain regulates food intake & feeding behaviour in response to input from circulating signals = ‘adiposity negative feedback’
Hormonal regulation of energy homeostasis
Leptin
Insulin
Ghrelin
Peptide YY (PYY) and Cholecystokinin (CCK)
Cortisol
How does Leptin impact hunger?
Produced by adipose tissue, leptin is a key hormone involved in long-term energy regulation.
When fat stores increase, leptin levels rise, signaling the brain that energy stores are sufficient. This leads to decreased hunger and increased energy expenditure.
When fat stores are low, the opposite occurs.
How does insulin impact hunger?
Insulin, produced by the pancreas in response to food intake, signals the hypothalamus to regulate energy balance.
High insulin levels signal the brain to reduce food intake and promote fat storage. Insulin also has an important role in promoting glucose uptake and fat synthesis.
Insulin resistance, can impair the brain’s response to insulin, contributing to increased appetite and reduced energy expenditure.
How does Ghrelin impact hunger?
Known as the “hunger hormone”, ghrelin is produced in the stomach, particularly during fasting or before meals.
Ghrelin levels rise when the stomach is empty and stimulate hunger by acting on the hypothalamus, especially on NPY/AgRP neurons, to increase food intake.
After eating, ghrelin levels decrease to signal satiety.
How do Peptide YY (PYY) and Cholecystokinin (CCK) impact hunger?
PYY is released by the intestines in response to food intake, particularly protein and fat. It helps reduce appetite by acting on the hypothalamus to promote satiety.
CCK is released from the gut after meals and has a short-term effect on reducing food intake by signaling to the brain that the stomach is full.
How does cortisol impact hunger?
Cortisol, the body’s primary stress hormone, can also affect energy homeostasis. Chronic stress leads to elevated cortisol levels, which can increase appetite, particularly for high-calorie foods, and promote fat storage.
5HT plays an important role in feeding behaviour
Serotonin plays a key role in regulating mood and appetite. Higher serotonin levels are associated with satiety and reduced food intake. Low serotonin levels, often seen in conditions like depression, may lead to increased food cravings, especially for carbohydrates.
Orlistat (Xenical, Alli)
Over the counter anti-obesity medication
Lipase inhibitor
Prevents the breakdown of dietary fats to fatty acids and glycerol
Decreases absorption of 30% of dietary fat
“Oily stools”, abdominal cramps, flatus with discharge
Produced a 2.9% greater reduction in body weight than placebo-controls; 12% more patients lost 10% or more of their body weight (Padwal et al. 2003)
Liraglutide /Semaglutide
Antidiabetic medicines
Analogues of incretin – glucagon-like peptide -1 (GLP1) bind to GLP1 receptor
Liraglutide (Saxenda) daily injection
Semaglutide (Wegovy) now available through NHS specialist weight management services – once weekly injection.
Fenfluramine
An amphetamine analogue marketed in 1970s as an anti-obesity drug, less potential for recreational abuse
A 5-HT releasing agent & reuptake inhibitor
Only produced moderate weight loss, effects temporary
Combined with phentermine in 1990s = “fen-phen”
But heart valve & pulmonary hypertension problems
Withdrawn in 1997, cost Wyeth > $7 billion in lawsuits
Phentermine
In the UK, not recommended for the treatment of obesity
Non-selective releasing agent of NA, 5HT and DA
Increases NA in the hypothalamus, stimulated b2-adrenergic receptors to induce appetite suppression
Inhibits monoamine oxidase potentiating 5HT and increasing basal metabolic rate
Associated with a risk of pulmonary hypertension
Withdrawn from the market in Europe
in 2001 over safety concerns and lack of evidence of sustained clinical benefit
