Obesity Flashcards
Describe 2 processes that increase fat mass
- Adipogenesis
- Increase in number of cells
- Controlled by PPARγ and C/EBPα (TFs)
- Differentiation of pre-adipocytes into terminally differentiated adipocytes
- More cells = more lipid can be stored - Increased lipid storage
- Increased glucose uptake into adipcutes through GLUT4
- VLDL taken up via LPL dependent process
- Non-esterified FFAs taken up via CD36 dependent process
- All for production of FAs and TAG
- Stored inside adipocytes, stabilised by perilipin
Describe 3 things involved in regulation of lipid storage
- Substrate availability
- Need FFAs, glucose, VLDL/TAG for lipogenesis - Sympathetic Nervous System
- Increased SNS activity = higher lipolysis (fat breakdown) and liberation of lipids from stored fat - Endocrine signals
- Different hormones influence different processes
Endocrine signals influencing lipid storage
Substrate availability: increased by insulin, prolactin, ghrelin, glucocorticoids / decreased by GH, leptin
Lipolysis: increased by adrenalin, glucocorticoids, glucagon, leptin / decreased by insulin
Adipogenesis: increased by glucocorticoids, mineralocorticoids, GH, IGF-1, prolactin, ghrelin / decreased by insulin
What is Irisin and its function
Hormone produced by muscle in response to exercise, switches on thermogenesis in brown adipose tissue. Switches on expression of beige fat - converting white adipose tissue into beige promotes utilisation rather than storage. FNDC5 expression increases in skeletal muscle in response to exercise and is cleaved to form Irisin.
Ways of measuring obesity/fat mass/etc
BMI = weight/height2 - a metric for measuring obesity but doesn’t account for body fat % or distribution.
WHR = waist:hip ratio - attempts to account for fat distribution but still could be subcutaneous or around organs etc. WHR > 1 = high risk of obesity
DEXA Scanning: X-ray to see where the fat is
MRI: fat-only image generated from a complete image and a fat suppressed image
Describe orexigenic molecules
Ghrelin: hormone that stimulates feeding, increases activity in NPY neurones
NPY: peptide produced from the ARC in response to signals from pancreas, GIT, and muscle - most powerful orexigenic peptide
Describe anorexigenic molecules
Leptin: inhibits feeding behaviour, produced by adipocytes in proportion to the amount of fat - a marker on the amount of energy stored
Peptide PYY: excites POMC neurones in the ARC
POMC/CART: expressed from neurones in the ARC that project to the PVN and prevent orexin release
Insulin: inhibits glucose, excites neurones in the ARC, most likely POMC
List 6 genetic conditions that increase susceptibility to obesity
Prader-Willi syndrome MC4-receptor mutation Leptin deficiency Leptin receptor deficiency Maternal under-nutrition Maternal over-nutrition
Describe Prader-Willi syndrome
Loss of paternally derived gene expression on 15q11-13 Epigenetic Affects 1 in 25,000 Always inherited from the father Neonatal/infantile hypotonia Hypogonadism Learning disabilities High levels of ghrelin Increased feeding/hyperphagia
Describe the relationship between leptin/receptor deficiencies and obesity
Leptin deficiency: leptin ΔG133 mutation deletes the leptin protein. Arises in consanguineous mating. Results in hyperphagia, hyperglycaemia, hyperinsulinaemia, increased pituitary hormone secretion, subfertile, obesity
Leptin receptor deficiency: hyperphagia, hyperphagia, hyperglycaemia, hyperinsulinaemia, polydipsia (thirst), polyuria, obesity
Describe the relationship between MC4-receptor mutation and obesity
Most common single mutation associated with obesity.
Receptor for melanocortin - produced by POMC, inhibits feeding.
Mutation in MC4-R prevents melanocortin binding so there is no inhibition of feeding. Satiety signal fails, resulting in a susceptibility to obesity.
Describe the relationship between maternal nutrition and obesity
Maternal under- and over- nutrition both lead to offspring obesity.
Maternal undernutrition: reduced ability to partition glucose to muscle so there is more available for fat. Less leptin signalling in the mother results in leptin resistance or blunted response in the baby - so eat more food.
Maternal over nutrition: placental inflammation results in increased lipid supply. Reduction in β-cell mass leads to a reduction in insulin, so there is more glucose available for fat storage. Increased differentiation in the hypothalamus leads to increased orexigenic expression and so continue to eat.
List 3 consequences of obesity
Type II diabetes
Cardiovascular disease
Reproductive issues
Describe the relationship between obesity and type II diabetes
Obesity causes a reduction in β-cell mass, so a reduction in insulin secretion. Circulating glucose is maintained at a higher level leading to hyperglycaemia. The pancreas is unable to maintain response leading to insulin resistance. The number of insulin receptors decreases and glucose levels in the blood continue to rise. There is more blood glucose available for fat storage. Increased TNF-α also inhibits activation of insulin receptors through inhibition of phosphorylation of IRS-1 - this is enhanced by increased resistin (a hormone from fat).
Describe the relationship between obesity and CVD
Insulin and leptin increase SNS activity. Enhances sodium reabsorption at the kidney, and so increased water retention. Leads to increase in blood pressure (hypertension). Increased angiotensinogen from white adipose tissues is converted to angiotensin, further increasing blood pressure. Due to increased fat there is also increased lipid in circulation.
