Obesity Flashcards
what is obesity?
- classified by BMI (>30 = obese)
- highly heritable ie. underpinned by genetics
- BMI = weight in kg/[height in m]^2
- it is a complex chronic disease defined by excessive fat deposits that can impair health
- obesity influences the quality of living, such as sleeping, moving and can have a negative impact on mental health
- obesity can lead to increased risk of type 2 diabetes, heart disease, stroke, impaired reproduction, liver and gall bladder disease respiratory disorders and certain cancers
- there is currently an obesity epidemic, the worldwide rates keep rising (NZ has the this highest obesity rate in the OECD, 1 in 3 adults is classed as obese, and 1 in 10 children is classed as obese)
What are the underlying causes of obesity?
Is it simple related to energy balance?
Eintake = Expended + Estored
Expended = basal metabolism + activities
Estored = weight gain
When energy intake is greater than energy expenditure (ie. a positive energy balance exists) the extra energy is stored as fat
What are the three possible ways that have been looked into for weight loss
- Reducing energy intake
- Increasing activities
- Increases basal metabolism
Describe how weight loss could be achieved by reducing energy intake
Reduce energy intake by: calorie restriction, low fat diet, low carb diet, blocking fat absorption (Xenical)
Reality:
- weight loss can be achieved but these diets can be hard to maintain
- furthermore, the body resets to a lower basal metabolism which makes it hard to maintain the weight loss
Describe ketogenic diets
- diets restricted in carbohydrates
- promote the use of body fat and ketosis
- reduces insulin secretion
- reduces appetite from satiety effect of protein
- heavily marketed for weight loss
- there are some concerns around removing healthy carbs ie. fruits (high in sugar) and pulses and grains
- keto diet based on saturated fats increase LDL levels
- data shows no more effective than low fat diets promoting weight loss
by what mechanism does xenical work for reducing energy intake
- Xenical, a pancreatic lipase inhibitor that reduces fat absorption was heavily marketed for weight loss
- it lost favour due to moderate weight loss win trials and many side-effects ie. leakage, gas and fatty stools
Describe how weight loss might be achieved by increasing activity
- excersise will not make you lose weight because when you excersise you get more hungry and eat more (increased activities but also increased energy intake)
- but it does have other benefits: cardiovascular and sensitivity to insulin
Describe how weight loss might be achieved by increasing basal metabolism
- increasing muscle mass because muscle is more metabolically active than fat and burns more ATP at rest
- uncouplers ie. substances that uncouple oxidative phosphorylation in the mitochondria, casing energy to be released as heat rather than generating ATP
Examples: - DNP and FCCP (cause hyperthermia and organ failure ie. very toxic)
- BAM 15 (shows promising results but still in pre-clinical trials stage)
- Uncoupling protein activators. Uncoupling proteins sit in the mitochondrial menebrane and are mostly found in brown adipose. when activated they promote generation of heat as opposed to ATP (associated with some heart problems)
- Thyroid hormones (also associated with some heart problems)
Why is obesity and how to manage it not that simple?
There are so many factors controlling your appetite and your metabolism ie. hormones.
- the brain is central to regulating food intake (hypothalamus), and it receives a lot of signals from metabolic tissues that controls what we eat
- negative feedback from leptin in adipose tissue to reduce appetite
- GIT also has feedback using GLP-1 (signals to reduce appetite to brain and stomach - slows gastric emptying)
- Meanwhile, ghrelin from the stomach signals that the gut is empty and stimulates appetite
what happens when you don’t have leptin (due to genes not working or something)?
- you will eat too much as no signals to brain from adipose tissue telling you to reduce energy intake
- leptin deficiency is rare but it does occur in humans, and can be fixed with leptin injections
- however, leptin doesn’t resolve obesity as it is leptin resistance that’s the problem
what are the two competing paradigms of obesity pathogenesis?
- Energy-balance model
- Hypothesis is that an increase in intake of energy dense foods, which promotes the reward system in the brain (makes you like it and want to eat more of that stuff) will result in a positive energy balance and promotes fat storage - Carbohydrate-Insulin model
- down to high carb diets being the problem because they promote insulin secretion and that promotes fat storage which then leads to a drop in circulating foods which stimulates the brain to eat. That’s when you get the positive energy balance.
The difference between the two models is where the positive energy balance lies (these models are also based on normal physiology
