1- physiology of feeding + satiety Flashcards
what is energy homeostasis?
- a physiological process whereby energy intake is matched to energy expenditure over time
- promotes body fuel stability - energy primarily stored as fat
how do you calculate BMI?
weight (kg)/square of height (m)
what are some consequences obesity?
- stroke
- respiratory disease
- heart disease
- osteoarthritis
- dementia
- covid-19
- diabetes
- cancer
why need fat?
- energy storage
- prevent starvation
- energy buffer during prolonged illness (when ill use up lots of energy so need it from stored fat)
what is consequence of disease of adipose tissue?
difficult to lose wight as over time (long term obesity) induces brain re-programming so your brain views the extra weight (fat) as normal + dieting as a threat to body survival
how does CNS influence energy and body weight?
1)Behaviour- feeding and physical activity
2)ANS activity- regulates energy expenditure
3)Neuroendocrine system- secretion of hormones
= site of integration of these factors is the brain, specific neural centre responsible is hypothalamus
what are 3 basic concepts underlying control system of body weight + energy intake?
- satiety signalling
- adiposity negative feedback signalling
- food reward
what is satiety?
= period of time between termination of 1 meal and initiation of the next
what is satiation?
= sensation of fullness generate during a meal
what is purpose of peptide hormones released during a meal?
variety of peptide hormones released by specialised cells in gut + stomach, they are released during a meal to limit meal size (can go wrong in obesity)
what are 3 examples of peptide hormones that are released during a meal to limit size?
- cholecystokinin (CCK)
- peptide YY (PYY3-36)
- glucagon-like peptide (GLP-1)
where is cholecystokinin (CKK) released from and what’s its function?
- secreted fromenteroendocrinecells in duodenum and jejunum.
- Released in proportion to lipids and proteins in meal.
- Signals via sensory nerves to hindbrain and stimulates hindbrain directly (nucleus of solitary tract (NTS))
where is peptide YY released from and what’s it’s function?
- secreted from endocrine mucosal L-cells of G-I tract.
- Levels increase rapidly post-prandially.
- Inhibits gastric motility, slows emptying and reduces food intake (Hypo)
where is glucagon like peptide released from and whats it’s function?
- product of pro-glucagon gene. Also released from L cells in response to food ingestion.
- Inhibits gastric emptying and reduces food intake (Hypo, NTS)
*GLP-1 important as this is target of anti-obesity drugs
what do signals respond to that control energy balance and where are they sensed?
- signals are produced in response to body nutritional status
- these are sensed in hypothalamus
- they act to modulate food intake + energy expenditure
what are 2 adiposity signals and what is their purpose?
leptin and insulin = act at hypothalamic neurons to say eat more or less →adiposity signals
what must be communicated in order to control energy status to control amount of body fat?
brain
what is leptin?
adiposity signal that is major one for controlling fat homeostasis in body
what is insulin?
adiposity signal, major control factor for glucose homeostasis (but can also control fat homeostasis a bit)
what is effect on adiposity signals as more fat is stored?
increased levels of adiposity signals as more fat stored
what does reduced leptin mimic?
mimic starvation, causing unrestrained appetite
(more leptin = lean. less leptin = large)
what is affect if deficient in normal functioning leptin receptor?
(plenty leptin but not functioning leptin) = obese and diabetic (hyperglycemic, hyperinsulinemic + insulin resistant)
*only explain less than 10% of obesity
what are biological roles of leptin (has multiple)?
- glucose homeostasis
- maintenance of immune system (relationship to covid)
- maintenance of reproductive system angiogenesis
- tumorigenesis
- bone formation
→so if leptin not working problem then big knock on effect
what is ghrelin?
a hunger signal - another satiety peptide, has long term influences on energy expenditure + weight
- it’s a octanoylated peptide, produced and secreted by oxyntic cells in stomach
how does ghrelin levels differ around meals?
increase before meals and decrease after meals (makes sense as hunger signal)
what can raise ghrelin levels?
Levels are raised by fasting and hypoglycaemia.
what does peripheral ghrelin stimulate? what is mechanism?
stimulates food intake, decreases energy expenditure and decreases fat utilization – increases body weight
- acts to trigger central pathways to prepare body to process in-coming nutrients –for storage as fat so helps control fat metabolism, increase lipogenesis and decreases lipid oxidation
what is effect of diet induced obesity on leptin?
leads to decreased leptin resistance
- most obesity is associated with high leptin levels (corresponds with high fat level) = this means leptin use therapeutically is reduced as high resistance
what are the 2 theories of why leptin resistance in diet induced obesity?
- Defective leptin transport into brain
- Altered signal transduction following leptin binding to its receptor
what are prevention options for diet induced obesity?
- Lifestyle changes: dieting and exercise – do not appear to produce marked sustainable weight loss in the overall population
- Psychological therapies – cognitive behavioural therapy – not able to deliver on a mass scale
- Bariatric surgery – effective – but reserved for morbidly obese. substantial weight loss and often resolves type 2 diabetes very quickly + effectively (not totally sure why)
- Therapeutic agents to reduce body weigh
what are therapeutic options for obesity?
- there have been previous drugs like noradrenergic, serotonergics, sibutramine, rimonabant which were effective but had extreme side effects
- GLP1 receptor agonists = more modern approach like luraglutide and semaglutide
what are examples of GLP1 receptor agonists for obesity therapeutic agents?
luraglutide = has to be injected, was originally given for diabetes but then discovered also gave weight loss
semaglutide = later development (better version) - very effective, 15-20% weight loss and reduced cardiovascular + heart disease, huge impact (the maker can’t keep up with demand, very popular)
→companies are trying to make oral versions of these drugs
