Control of body weight Flashcards
Describe the homeostatic control of body weight inputs
- Adiposity signals from adipose tissue
- Satiety signals from GIT
- Hunger signals from GIT
- signals coalesce on hypothalamus and brainstem
note this system is very accurate
Describe the adiposity signals and their actions
- i.e. leptin and insulin, signals from stored and available fuel respectively ^[adiponectin, another potential adiposity signal, poorly understood]
- these must signal to brain i.e. cross BBB, bind receptors in order to change food intake and energy expenditure
Leptin - Gk leptos = thin
- Concentration in blood increases in proportion to body fat
- Secreted primarily by adipocytes in white fat
Insulin
- Released by β-pancreatic cells in response to glucose in blood
- However, the basal level of insulin and the total area under the 24 hr insulin curve are excellent indicators of adiposity
- i.e. basal levels higher in obesity
Comparison of Leptin & Insulin
- Leptin:
- Stable signal; t1/2 45 mins
- Correlates with subcutaneous fat
- Insulin:
- Changing signal; t1/2 2-3 mins
- Correlates with visceral fat -> plasma insulin a better predictor of metabolic disorders to Brain: predominantly arcuate nucleus of hypothalamus
Central actions of leptin & insulin
- If caloric intake< expenditure i.e. E balance is negative
- low insulin and leptin
- enhances anabolic activity and inhibits catabolic activity
- increased food intake and weight gain
- If caloric intake > expenditure i.e. E balance is positive
- high insulin and leptin
- enhances catabolic activity and inhibits anabolic activity
- decreased food intake, and weight loss
- Anabolic = build up of tissue; Catabolic = breakdown of complex substrates
Describe the hypothalamus nuclei involved in weight and appetite regulation
Hypothalamus
- key regions of the hypothalamus play a role in the homeostatic regulation of appetite
- ArNu= arcuate nucleus
- PvNu = paraventricular nucleus
- LHA = lateral hypothalamic area
### 1st Order Neurones: Arcuate Nucleus of Hypothalamus
- NPY = neuropeptide Y
- AGRP = agouti-related protein
- The above hormones promote appetite, decreasing metabolism and energy expenditure
- POMC = pro-opiomelanocortin
- Endorphins and melanocortins
- α-melanocyte SH (MSH)
- The above hormone promotes appetite suppression
- Leptin and insulin bind to their respective receptors on the NPY/AGRP-ergic and POMC-ergic neurons
- stimulating POMC-ergic neurons
- inhibiting NPY-AGRP-ergic neurons
- these neurons then release/don’t release their respective neurotransmitters which bind to the receptors on downstream target neurons
Tonic Metabolic Effectors
- NPY/AGRP are orexogenic molecules (anabolic effectors):
- INCREASE food intake
- DECREASE energy expenditure
- MSH is anorexogenic molecules ie catabolic effectors:
- DECREASE food intake
- INCREASE energy expenditure
2nd Order Neurones of Hypothalamus
- PVN = Paraventricular nucleus; ‘satiety centre’; releases the following substances involved in control of body weight:
- TRH = Thyrotrophin releasing hormone
- CRH = Corticotrophin releasing hormone
- LHA = Lateral hypothalamic area; ‘hunger centre’;
- Contain the following substances involved in control of body weight:
- ORX = Orexin
- MCH = Melanin concentrating hormone
NPY/AGRP-ergic neurons and POMC/CART-ergic neurons, based on stimulation or inhibition from leptin/insulin, signal bilaterally on PVN and LHA/PFA to stimulate the release of hormones listed above (TRH, CRH; ORX, MCH).
The balance of NPY/AGRP vs POMC/CART stimulation of second order neurons determines the sensation of satiety or hunger.
Describe the role of satiety signals, their origin and their effect of appetite regulation
- Must regulate meal frequency and/or size to maintain energy balance
- Major determinant of meal size is onset of satiety:
- ‘a biological state induced by neurohumoral stimuli generated during food ingestion that leads to eating termination’
- Signals arising from gut => brainstem and/or hypothalamus
Origin of Satiety Signals
- Mechanical
- Direct stimulation of stretch receptors whose axons are in vagus
- Food chemicals => Cholecystokinin (CCK) release from I cells of duodenum, jejunum (for revision go to [[Physiology B5 - Lecture 1]], [[Physiology B5 - Lecture 2]], [[Physiology B5 - Lecture 3]])
- stimulates receptors on vagal axon terminals => REDUCE FOOD INTAKE
Origin of Satiety Signals cont
- Food chemicals => stimulation of neuroendocrine secretory cells in GI tract:
- Free fatty acids, glucose and carbohydrate => glucagon-like peptide 1 (GLP-1) and oxyntomodulin (OXM) secretion from L cells of small intestine => REDUCE FOOD INTAKE
- Fat => glucose-dependent insulinotropic polypeptide (GIP) secretion from K cells of duodenum, jejunum => variety of actions including increased insulin secretion
- Food => peptide YY (PYY) secretion from L cells in ileum, colon, and rectum => REDUCE FOOD INTAKE
- Food => pancreatic peptide (PP) and amylin secretion from specific pancreatic islet cells, exocrine pancreas, and distal GIT => REDUCE FOOD INTAKE
Satiety Signalling to Brain
- small ‘hedonic input’
- largely vagal i.e. DVC
- hormonal i.e. CCK, ghrelin; PYY and OXM; GLP-1 and GIP; insulin and leptin –> brainstem and hypothalamus
- Overall effect: meal timing, meal size, energy expenditure
Describe ghrelin and its role
Ghrelin: ‘Hunger Hormone’ ^[side note, only one identified hormone whose sole object is “eat” many more needed to STOP]
- Synthesized in cells throughout GI tract but highest density at fundus of stomach
- Plasma levels rise immediately before meals but fall within 1 hr of food intake; also high during fasting (and in anorexics and thin people)
- Ghrelin activates:
- NPY receptors of ARC nucleus to stimulate feeding (opposite effects to leptin and insulin)
- Vagal afferents to stimulate feeding (via brain), as well as to stimulate gastric acid secretion and gut motility
- rises before meals, rises in basal level during night
- in obese- less diurnal fluctuation and lower ghrelin baseline
An aside: why has public health failed to reverse trends in obesity and diabetes?
- Sumithran et al, 2011
- 10 week intensive weight loss program, starting at 95 kg
- losing about 12 kg
- regaining about 7 kg by the end of the year
- ratings of hunger and desire to eat bounced right back to pre-study baseline
- ghrelin postprandial is higher, PPY lower, amylin and CCK lower
- in other words ‘long term persistence of hormonal adaptations to weight loss’ which is difficult to overcome
