Liver and Adipose tissue lecture Flashcards
What are the four functions of adipose tissue?
Mechanical cushioning
Thermal insulation
Energy Store
Endocrine Organ
Why do children need more brown adipose tissue than adults?
Children have a higher SA:V ratio
What is the fat related function of white adipose tissue?
Controlled storage and release of fat
What cell type does brown adipose tissue develop from?
Muscle cell progenitors
How are fatty acids stored?
Converted into triglycerides
Mainly found in adipose tissue
Can also be found in the liver and muscle
What is the structure of triglycerides?
A molecule of glycerol and three fatty acid chains, that each join to G by ester bonds
Fatty acid chains tend to be saturated
What is the oxygen demand of the adipocyte?
Very low oxygen demand
What percentage of body weight tends to be white adipose tissue?
20%
In the fed state what is the process of fat metabolism in the white adipose tissue?
FA transported to adipose tissue by blood from the liver in VLDL.
Glucose is also transported to adipose tissue
In the adipose tissue glycerol and FA combine to form TG, for storage
This is an anabolic process regulated by insulin.
In the fast state what is the process of fat metabolism in the white adipose tissue?
TG are broken down into FA and glyercol by HSL (Hormone sensitive lipase).
Fatty acids bind to albumin to be transported back to the liver in the blood - then converted to Acetyl-CoA (beta oxidation) as a source for gluconeogenesis.
Glycerol can also be converted to glucose in the liver.
This is a catabolic process regulated by adrenalin and glucagon
What is the role of the liver in FA metabolism in the fast state?
FA enter from adipose tissue - undergoe beta oxidation to produce Acetyl-CoA to enter Krebs
Acetyl-CoA may also be converted to pyruvate (then glucose).
Acetyl-CoA can be converted into ketones if Krebs is saturated
What is the role of ketone bodies in FA metabolism?
Reversible - made from acetyl-CoA (product of beta oxidation)
Increases levels of beta oxidation
Is stimulated by fasting, high fat diet, vigorous exercise, excess alcohol and lack on insulin.
What is the role of muscle in FA metabolism in the fasted state?
Uses FA and ketone bodies for energy production (preserves glucose for the brain)
Also used in times of increased demand such as high intensity exercise
What is the Cori cycle in the muscle?
Glucose enters the muscle
By anaerobic respiration is converted to pyruvate then lactate.
Lactate is recyled back to the liver where is can to restored back to pyruvate then glucose (repeate cycle) or acetyl CoA.
What is the precursor cell for white adipose tissue?
Fibroblast-like precursor cell - recieves hormones that trigger to develop into adpicoytes.
Explain the process by which mature fat cells develop?
Develop from a fibroblast-like precursor cell
Gene expression is alters and beings to accumulate lipid droplets
Lipid droplets accumulate and merge to form a mature fat cell with one large lipid droplet and a peripheral nuclei.
Mature fat cells can not proliferate but the stages in development are reversible.
What changes occur in white adipose tissue when a person gains weight?
Cells increase in size (hypertrophy)
New cells are made
There is no upper limit to the amount of white adipose tissue a person can have
What is the thrifty gene hypothesis of obesity trends?
Certain groups are more likely to be obese as their genes predispose them to be good at storing adipose tissue.
Historically would have been evolutionary advantagous to store lots of fat during summer to prepare for lack of harvest over winter.
However, in modern times when food is readily available this is causing a rise in obesity and type 2 diabetes.
How do adipocytes change in obesity?
Modest weight gain - lipid droplet and cell increases in size until maximum size is reached
More weight gain - recruit pre-adipocytes to differentiate, the number of adipocytes increases
Process repeats
What happens to adipocytes during weight loss?
Cells decrease in size but do not decrease in number
Why is white adipose tissue considered an endocrine organ?
Produces steroid hormones - oestrogen and cortisol
Proteins of energy metabolism, blood clotting and complement pathway
Cytokines
Peptide hormones (leptin)
What are the different leptin genes how are they important in obesity rates?
ob gene - leptin
db gene - leptin receptor
Failure to express these genes, unable to recongise fullness, so continues to eat compulsivly and becomes morbidly obese.
How does leptin relate to adipose tissue?
Link to obesity
Is produced by adipose tissue
Greater proportion of adipose tissue will give you a greater proportion of leptin - in theory this should decrease hunger and reverse obseity
However, obese individuals often develop resistance to leptin so hunger is not resolved.
Who would benefit from leptin as an anti-obesity drug?
Those with an ob/ob mutation so are unable to produce leptin.
What processes is leptin important for regulating?
Appetite
Metabolic rate
Reproduction
What is the role of adiponectin?
Linked to obesity
Higher adipose tissue = less adiponectin
- promotes glucose production in the liver
- promotes glucose oxidation in the muscles
What is the role of resistin?
Linked to obesity
Promotes insulib resistance
Increased levels in obese patients
What is the role of TNFa
Linked to obesity and white adipose tissue?
Impairs insulin signalling and glucose transport
Is a pro-inflammatory cytokine increases insuline resistance
Levels increase with obesity
What is the role of IL-6?
Linked to obesity.
Pro-inflammatory cytokine
Increases lipolysis and glucose uptake
Acute phase response protein
What is the endocrine role of FA?
Linked to obesity?
Impairs insulin production
Causes insulin resistance
Functioning on pancreas is very sensitive to excess adipose tissue
What are the two parts of the hypothalamus that are important in weight regulation?
Lateral hypothalamus - releases hunger signals
Ventromedial hypothalamus - feels fulls and content
What signals from the digestive tract will increase apetite?
Ghrelin - released from an empty stomach
What is the role of pancreatic polypeptide?
Released from the pancreas when the duodenum is distended
Decreases appetite and delays gastric emptying
What is the role of CCK Cholecystokinin?
Released after a meal to aid digestion and reduce apetite.
Inhibits lipolysis in the gur
What is the role of RBP4 and adiponectin in obesity?
RBP4 - reduces tissue insulin sensitivity
Would normally be antagonised by adiponectin, however adiponectin levels drop during obesity
What neurotransmitters act within the hypothalamus to regulate apetite and food intake?
Neuropeptide Y
Agouti-related peptide
Pro-opiomelanocortin
What is the role of neuropeptide NPY in obesity?
NT
- increase food intake
- decrease physcial activity
What is the role of agouti-related peptide AgRP in obesity?
- increase apetite
- decrease metabolism
What is the role of pro-opiomelanocortin in obesity?
POMC
pre-cursor
regulates melanocyte sstimulating hormone levels
Regulates appetite and sexual behaviour
How do gut hormones affect the hypothalamus in the fed state?
Insulin and leptin
Inhibit NPY/AgRP neurones in the hypothalamus
How do gut hormones affect the hypothalamus in the fasting stage?
Ghrelin
Activates NPY and AgRP neurones in the hypothalamus
What are the hormonal differences between fat and thin adipocytes?
Fat (larger lipid droplet) - insulin resistance, chronic inflammation, T2D, high BP, cardiovascular disease and cancer risk
Thin (small lipid droplet) - benign regulation of metabolic tissue, release adiponectin to promote glucose uptake
How is glucose metabolised in white adipose tissue in fed state?
Elevated insulin levels - glucose influx into adipocyte
Glycolysis - supplies glycerol phsophate for TG synthesis
Increases hexose monophosphate pathway - promotes NADPH needed for fat synthesis
Glucose is stored as TG
How is fat metabolised in white adipocytes in the fed state?
Fatty acids as synthesised from acetyl-CoA during fed state
Elevated insulin levels favours inacitve state of hormone sensitive lipase so reduces TG degradation
Leads to an accumulation of TG in white adipose tissue.
How is glucose metabolised in white adipose tissue in the fast state?
Glucagon and adrenaline
Decrease glucose transport and metabolism leading to a decrease in FA and TG synthesis in WA tissue.
How is fat metabolised in white adipose tissue in the fast state?
Glucagon and adrenaline promote hormone-sensitive lipase to break down TG.
FA are released via the blood stream for other tissues to use as an energy source
Glycerol is released via the blood and used for gluconeogenesis in the liver.
What are the key differences between visceral and subcuntaneous fat?
Visceral - surrounds abdominal organs, problematic signals to the liver causing insulin resistance, is more metabolically active
Subcuntaneous - less metabollically acitve so less effect on liver function
What are the different body shapes based on fat distribution?
What is the largest risk for T2D?
Android - upper body obesity, men and post menopausal women, highly metabolically active - insulin reistance
Ovoid - overall obesity, often a genetic disposition
Gynoid - low body obesity, common in pre-menopausal women, benign metabolic effect, not easily mobilised and can be hard to loose weight
What systems are responsible for long term regulation of body fat?
Hormonal, metabolic and neural
Adipose tissue - messenger system of how much is stored
Translation system in the brain - is this the right amount
Effector system - musckes and GI tract - adjust energy expenditure and intake
