Physiology: Feeding & Satiety Flashcards
What physiological imbalance leads to obesity?
Small constant mismatch between energy intake and energy expenditure
What is energy homeostasis?
over time energy intake is matched to energy expenditure
Obesity BMI range
Up to 25 -> normal
25 - 29.9 -> overweight
30 - 39.9 -> obese
> 40 -> morbidly obese
Describe obesity as a disease
group of conditions with multiple causes
What are the major factors influencing obesity? (2)
- Genetics (susceptibility genes linked to fat storage and also regulation of energy intake and expenditure)
- Environment (wide variety of high calorie food, reduced physical activity e.g. cars, jobs)
What are some diseases does obesity contributes to? (11)
- Stroke (hypertension)
- Dementia (Alzheimer’s)
- Respiratory disease (sleep apnoea)
- Type 2 Diabetes
- Hypertension
- Cardiovascular disease (lipids, diabetes, hypertension)
- Increased cancer risk (especially colon, breast, uterus, prostate)
- NAFLD (Non-Alcoholic Fatty Liver Disease)
- Gall bladder disease
- Osteoarthritis
- Hyperuricaemia -> gout
Functions of fat (3)
- Energy storage
- Prevention of starvation
- Energy buffer during prolonged illness
How does the brain respond to long-term obesity?
Brain defends body weight because it views the new weight as normal and dieting as threat of starvation.
In what 3 ways does the CNS influence energy balance and body weight? What is the site of integration of these influences and what is the neural centre responsible?
- Behaviour - feeding and physical activity
- ANS - regulates energy expenditure
- Hormonal - secretions of hormones
Site of integration: brain
Neural centre responsible: hypothalamus
Lesioning of which part of the hypothalamus causes obesity?
Ventromedial
Lesioning of which part of the hypothalamus causes leanness?
Lateral (lateral leanness)
Define satiation.
Define satiety.
Define adiposity.
Satiation: sense of fullness generated during a meal. (signals increase during meal time to limit meal size)
Satiety: period of time between meals. (satimety)
Adiposity: the state of being obese.
What 3 concepts underlie the control of energy intake and body weight?
- Satiety signalling
- Adiposity negative feedback signalling
- Food reward
What are the 5 Satiation Signals and discuss their location of secretion, release, and action?
- Cholecystokinin
- secreted from enteroendocrine cells in duodenum and jejenum.
- released in proportion to lipids and proteins in a meal.
- signals via sensory nerves to hindbrain and stimulates hindbrain directly (Nucleus of solitary tract NTS) - Peptide YY (PYY3-36)
- secreted from endocrine mucosal L-cells of GI tract
- release increases post-prandially
- inhibits gastric motility, slows emptying and reduces food intake (hypothalamus) - Glucagon-like Peptide 1 (GLP-1)
- product of pro-glucagon gene
- released from L cells in response to food ingestion
- inhibits gastric emptying and reduces food intake (hypothalamus, NTS) - Oxyntomodulin (OXM)
- from pro-glucagon gene, and small intestinal L cells and oxyntic cells
- released after meal
- acts to suppress appetite - Obestatin
- peptide produced from gene that encodes ghrelin
- released from cells lining the stomach and small intestine
- not sure but may reduce food intake and antagonise action of ghrelin
What is the hunger signal? What produces it? When is it produced? How are its levels raised?
Ghrelin
- produced + secreted by oxyntic cells in stomach
- levels increase before meals and decrease after.
- levels raised by fasting and hypoglycaemia
What does peripheral ghrelin do?
- stimulates food intake
- decreases energy expenditure
- decreases fat utilisation
overall increases body weight
What do ghrelin-containing hormones in brain do?
- helps control fat metabolism
- increases lipogenesis
- decreases lipid oxidation (liver and adipose) (lipid oxidation causes cell damage)
What can be injected into hypothalamic centres to increase food intake? (3)
-Glutamate
-gaba
-opioids.
Effects are short lasting.
What neurotransmitters suppress food intake?
Monoamines (drugs developed based on these systems but most withdrawn with bad side effects)
What are the two adiposity signals (reporting fat status), where are they produced and what do they act on?
Leptin (produced in fat cells) and Insulin (produced in beta pancreatic cells)
Act on hypothalamic neurons.
Levels of these increase in blood with increase in fat.
What happens with reduced leptin?
Reduced leptin mimics starvation -> unrestrained appetite
Where are there high levels of leptin receptors?
Hypothalamus
List biological roles of leptin
- food intake/energy expenditure/fat deposition
- peripheral glucose homeostasis/insulin sensitivity
- immune system maintenance
- reproductive system maintenance
- angiogenesis
- tumourgenesis
- bone formation
What therapy can be effective in ob defected people? In what group of people is it ineffective?
Injected leptin therapy
Ineffective in people with leptin resistance
What can cause leptin resistance?
diet-induced obesity (defected leptin transport + problem with leptin receptors)
List some anti-obesity drugs (4)
- sibutramine (decreases food intake, withdrawn but can still be bought online)
- Orlistat (reduces fat absorption in small intestine, bad gastric side effects, need vitamins at same time, approved in europe, over the counter)
- Contrave/Mysimba (approved in europe)
- Liraglutide (drug used for type 2 diabetes that is a GLP-1 agonist + shows weight loss effects at high dose, has to be injected)
What surgery is performed for obesity?
Bariatric surgery - gastric by-pass (50-60% weight loss, Type 2 diabetes resolution, reduced calorie intake because of by-pass but also altered secretion of peptides from stomach that affects hypothalamus and beta cells, e.g. PPY3-36, GLP-1, ghrelin
What are some metabolic stress consequences
- obesity
- dyslipidaemia
- Type 2 Diabetes
- Insulin Resistance
- Metabolic Syndrome
- CVS disease
