Adipose Hormones (9) Flashcards
What is adipose tissue?
Body fat → stores energy in the form of fat, which can be used in times of low food intake or high energy usage
WAT → white adipose tissue
→ large spherical adipocytes, storage of lipids as triglycerides
→ beneath the skin - subcutaneous fat
→ around internal organs - visceral fat
→ as lipids accumulate adipocytes can enlarge or increase in number from stem cells
How does insulin contribute to adipogenesis?
Preadipocytes become mature adipocytes when stimulated by glucose/insulin ‘fed state’
→ promotes expression of genes involved in adipocytes differentiation
What is metabolic syndrome?
Cluster of interconnected metabolic disorders closely associated with visceral obesity
→ BMI, fat %, glucose levels, changes to bp
What is subcutaneous fat?
Adipose tissue located directly beneath the skin
→ formed from mesodermal stem cells
→ fat storage and insulin
→ secretes adipokines
What are some adipose derived hormones?
2 main → leptin (increased in obesity)
→ adiponectin (decreased in obesity)
also angiotensinogen, chimeric, cytokines (high adipose tends to drive inflammatory response)
What is leptin?
Hormone mainly produced why adipose cells that plays a key role in energy balance and body weight
→ signals to brain, released to bloodstream when fat cells store excess energy
→ binds to receptors in hypothalamus where it sends signals to suppress appetite and increase energy expenditure
→ in obesity leptin resistance can occur - dysregulation of appetite and energy
How does leptin signal?
Leptin is released by adipose into blood stream
→ crosses BBB to the hypothalamus
→ binds to receptor tyrosine kinase - leptin receptors
→ activates JAK-STAT pathway - leads to phosphorylation of STATS which enter nucleus
→ regulates expression of various genes
What is the difference between leptin and ghrelin?
Both key hormones involved in regulating appetite and energy balance but have contrasting roles
Leptin → satiety hormone released by adipose tissue
Ghrelin → hunger hormone released by stomach
What are endospanins?
Transmembrane proteins found on the cell membrane
→ involved in controlling receptors availability to the endosome
→ sit on membrane and guide where receptor can come off the membrane onto endosome - internalised, recycled or replaces
Decrease in endospanin 1 → more receptor at membrane, increased leptin signals
Increase in endospanin 1 → increase in degradation of receptor, lack of satiety signals (high circulating levels in obese humans)
→ potential therapeutic to intervene leptin signals
What is adiponectin?
244aa protein hormone (adipokine) secreted by adipose tissue
→ secretion caused by insulin
→ reduced in obesity - promotes insulin resistance
→ promotes glucose uptake
→ inhibits gluconeogenesis
→ promotes fatty acid oxidation - uses fat storage
→ complementary and additive effects with leptin
→ complex trimer - many potential therapeutic targets
key role in regulating metabolic health
What is involved in adiponectin signalling?
Primarily signals through two unusual (upside down GPCRs) receptors:
→ ADIPOR1 (skeletal muscle)
→ ADIPOR2 (liver)
signal to mainly AMPK and others
→ AMPK is a key cellular energy sensor - signals mitosis, change gene expression
adiponectin exists in many forms
→ ADIPOR2 has low affinity for the trimer
What disorders is adiponectin linked to?
Muscle → insulin resistance
Artery → atherosclerosis, intimal hyperplasia
Capillary → impaired angiogenesis, endothelial dysfunction
Heart → cardiovascular disease, pathological hypertrophy, ischemic injury
What are adipokines?
Group of hormones and cytokines primary released by white adipose tissue that playing important roles in metabolism, inflammation, immune function
→ communication between adipose tissue and other organs
→ coordinate responses to change in energy status, nutrient availability and metabolic demands
examples; leptin, resistin, visfatin, chemokines, fatty acids, cholesterol
dysregulation linked to type 2 diabetes, cardiovascular disease etc
