Beyond the Classic Endocrine Glands Flashcards
how do adipocytes store energy?
as triglycerides and release energy and free fatty acids
what are two key enzymes?
lipoprotein lipase and hormone sensitive lipase
what is lipoprotein lipase?
found on outside of fat cells, stimulated by insulin leading to uptake of fatty acids in the circulation for storage
which form do circulating lipids take?
FFA bound to serum proteins, but mostly part of lipoproteins.
what are other sources of TAGs?
chylomicrons containing newly digested ones or VLDLs from the liver
what does LPL do?
hydrolyse TAG into FFA and glycerol, taken up and resynthesised into TAG and stored
what are TAGs?
triacylglycerides
what happens when there is too much glucose?
when theres more than can be put into glycogenesis, glucose is taken up by adipocytes and synthesised into glycerol or acetyl CoA –> TAG
how is energy released from TAG?
hydrolysis into FFA and Glycerol released into circulation via hormone senstive lipase enzyme
why is it called hormone sensitive lipase?
activity is stimulated by hormones such as adrenaline and cortisol
why is the energy storage more of a problem?
this is associated with the obesity epidemic
what hormones are released by the adipose tissue?
- leptin
- adiponectin
- resistin
what do the hormones released by adipose tissue do?
act as distant targets so are therefore hormones
What is leptin?
hormone released by fat cells acting on hypothalamus receptors to trigger pathways associated with satiety. Causes response that we dont need more fat and can instead burn energy = -ve feedback
why is the leptin response negative feedback?
the leptin triggers a turn down in lipogenesis and turn down in appetite behaviour
why does leptin not work in obese people for weight loss?
obesity is more a problem with leptin resistance and high leptin rather than mutated leptin
what do weak androgens released by adrenal gland do?
convert into strong androgens and also convert androgens into oestrogens
what type of signalling molecule are cytokines?
paracrine but some can enter into circulation
what other hormones are released from adipose tissue?
adiponectin and resistin
what does adiponectin do?
potentiates insulin to maintain and increase sensitivity. in obesity, adiponectin levels decrease which compromises effectiveness of insulin
what is resistin associated with?
insulin resistance, high in obesity
what happens where obesity is associated with insulin resistance?
likely raised insulin levels –> chronic hyperinsulinaemia
what can insulin stimulate release of?
IGF-1
what do adipocytes do in obesity?
release more pro-inflammatory cytokines
normal fat cell?
high adiponectin, low leptin
obese fat cell?
low adiponectin, high leptin resistance, high resistin and more immune cells due to chemokines secreted by fat cells bringing in more macrophages.
implication of more adipose tissue
more macrophages so adipose tissue is in a semi-inflammatory state
why is there insulin resistance in obese individuals?
lots of leptin release but lots of leptin resistance, adiponectin levels decrease contributing to insulin resistance and while resistin increases, it also contributes to insulin resistance.
what is metabolic syndrome?
disorder of energy metabolism
what is metabolic syndrome associated with?
- obesity
- hypertension
- raised serum glucose
- high serum triglycerides
- insulin resistance
which type of fat is worse?
visceral rather than subcutaneous
what is ghrelin?
hormone released from stomach, promotes feeding
where is leptin released?
adipocytes
where do vagal afferents travel?
nucleas tractus solitarius
what do leptin and vagal afferents signal to hypothalamus?
satiety so that hypothalamus integrates and moves towards burning fat/conserving
what increases during absorptive phase?
leptin, insulin, PPY, CCK, GLP-1
what do leptin, insulin, PPY, CCK, GLP-1 do>
stimulate neurones in hypothalamus leading to anorexigenic effect to inhibit food intake
what does ghrelin do?
stimulates various neural pathways in hypothalamus leading to orexigenic effect to stimulate food intake
anorexigenic effect?
inhibits food intake
orexigenic effect?
stimualtes food intake
what does reducing leptin do?
increases appetite
what is ghrelin good at?
appetite stimulation
what does mutation in LEP (leptin) gene, adipose tissue or LEPR (leptin receptor) lead to?
abnormal eating behaviour and early onset morbid obesity
how can leptin deficiency be treated?
with leptin to result in reduced fat mass
why is leptin treatment rarely effective?
single mutations are rare, its usually much more complex
what is obesity associated with?
leptin resistance
what is renin?
enzyme produced by kidney which can cleave pro-hormones in the circulation
what hormone can heart cells release?
atrial natruiuretic peptide (ANP)
when is ANP released?
in response to atrial stretch
when does atrial stretch occur?
raised BP due to raised blood volume = greater venous return = greater stretching
what are the aims of ANP?
to oppose/inhibit the RAAS system
what are the effects of ANP?
- vasodilation to reduce BP
- inhibits Na+ absorption is kidney promoting diuresis
- modulates the RAAS system by inhibiting renin so less Ang II and aldosterone which would usually increased blood volume and BP
what does renin do?
converts Angiotensinogen to Angiotensin I so that Ang I –> Ang II via ACE
when is renin produced?
in response to low perfusion pressure, reduced Na+ or sympathetic stimulation
what does angiotensin II do?
lowers BP via vasoconstriction and stimulating adrenal cortex to secrete aldosterone
how does aldosterone work?
increases salt and water retention in kidneys increasing blood volume and blood pressure
what is erythropoietin?
hormone release by kidney in response to low partial pressure of oxygen in circulation
what does erythropoitein do?
stimulates bone marrow to produce more RBC
what is recombinant EPO?
used to treat anemia due to renal failure
what is calcitriol?
hormone that synthesises active Vitamin D. Conversion into calcitriol by an enzyme happens in kidney
what is the function of vitamin d?
calcium homeostasis, if calcium levels drop, activity of enzyme increases and more vitamin D released
what are the effects of vitamin d?
increase absorption of Ca2+ from the gut and releases Ca2+ from bone raising Ca2+ levels.
parathyroid hormone
also involved in calcium homeostasis
what is main store of calcium?
bone
what do osteocytes produced?
fibroblast growth factor 21 (FG23) which decreases absorption of phosphate and synthesis of active vitamin D when it reaches kidney
what do osteoblasts produce?
uncarboxylated osteocalcin (uOCN)
what does uOCN do?
increases insulin production and secretion in pancreatic beta cells increasing adiponectin secretion (potentiates insulin in adipocytes) and increases insulin sensitivity and glucose uptake in muscle
examples of tumours that increase secretion of hormone?
pituitary adenoma, increased corticotrophs = cushing disease
tumours can be ectopic source of hormone
e.g. lung tumours secrete ACTH and stimulate cortisol secretion outside of normal gland release.
what tumours are hormone dependent?
breast and prostate cancer
what do hormone dependent tumours do?
convert circulating precursors into biologically active steroids that stimulate their own growth
breast tumours convert weak androgens to oestrogen
allows tumour to keep growing
what is oestradiol?
active end product, used to therapeutically target enzymes to stop production of hormones to stop growth
what is circadian rhythm controlled by?
melatonin secreted from pineal gland?
what are circadian rhythms?
bodys biological clock
how are circadian rhythms secreted?
in a rhythmic pattern, low in the day, rise at night
what does circadian rhythm correlate with?
physiological functions e.g. body temp drop during sleep and decrease in alertness at night
why are circadian rhythms endogenous?
not entrained to light-dark cycle instead they run on 24 hour cycle
how can circadian rhythms be influenced?
via sensory input from environmental cues
what controls circadian rhythm and has neural links to pineal gland?
suprachiasmatic nucleus
