S2: Beyond the Classical Endocrine Glands Flashcards
What are the two key enzymes that adipocytes have to release energy from stored triglycerides as free fatty acids?
- Lipoprotein lipase found on the outside of fat cells
2. Hormone sensitive lipase on the inside
Describe lipoprotein lipase
- Lipoprotein lipase can be stimulated by insulin and lead to the uptake of fatty acids in the circulation for storage
- ## LPL is a lipase so actually hydrolyses the TAG into FFA and glycerol and taken up into cell to be resynthesised into TAG and stored
What forms can circulating lipids take?
Circulating lipids can be in the form of FFA in which case they would be bound to serum proteins. But mostly they are part of lipoproteins, so chylomicrons which contain newly digested ones or VLDLs from the liver. These are sources of TAGs.
How can TAG be used to release energy?
What enzyme is needed?
In order to release energy, the stored TAG can be broken down (undergo hydrolysis) and FFA and glycerol released into the circulation, for energy use (so this process is energy releasing). It is hormone sensitive lipase that allows this to happen. It is called hormone sensitive because its activity can be stimulated by hormones such as adrenaline and cortisol.
List some hormones released by adipose tissue
Leptin
Adiponectin
Resistin
Role of leptin
Leptin is released by fat cells and acts on receptors on the hypothalamus where it triggers pathways that are associated with satiety (fullness). It triggers pathways that say we don’t need more fat, we can start burning energy.
It is a type of negative feedback, as adipose stores increase they release leptin which triggers metabolic pathways that turn down lipogenesis and turn down appetite behaviour.
Can leptin be a treatment for obese people?
Not really as only a small minority of obese people have an actual mutation with leptin. minority had an actual mutation with leptin. For most obese people it was more complex and instead associated with very high leptin levels and leptin resistance.
Role of Adiponectin and Resistin
Adiponectin seems to be a hormone that potentiates insulin, seems to be needed to maintain insulin sensitivity and can increase sensitivity. We know in obesity that adiponectin levels decrease, which can compromise insulin effectiveness (as remember obesity is associated with insulin resistance).
Resistin seems to be associated with insuin resistance, in obesity resistin levels go up.
Why can sex hormones be converted?
Weak androgens produced by the adrenal glands don’t have much biological function, however they can be converted in various tissues, especially in adipose tissue. Notably they can convert weak androgens to strong androgens and androgens to oestrogens.
How can obesity change a body?
- Associated with insulin resistance and raised insulin levels (chronic hyperinsulinaemia)
- Insulin can release other factors such as IGF-1
- Adipocytes in obesity tend to release more pro-inflammatory cytokines in obesity
- There is a large amount of leptin release, but they have leptin resistance. Adiponectin levels are decreased which can contribute to insulin resistance (inversely correlated) while resistin is increased (positively correlated), which can also contribute to insulin resistance.
Compare fat cells of normal and obese body
Fat cells in a normal, lean body mass tend to be smaller with fewer macrophages. High adiponectin, lower leptin.
In obesity (on right), the number of immune cells (particularly macrophages) increases, this is due to chemokines secreted by fat cells which bring in more macrophages etc.
So with more adipose tissue, and that more adipose bringing more macrophages. So in obesity, adipose tissue is in a semi-inflammatory state, which can be associated with some of the complications of obesity.
Describe Metabolic Syndrome
Metabolic syndrome is a disorder of energy metabolism, in particular energy storage and is associated with a number of factors:
- Obesity (especially visceral/abdominal)
- Hypertension
- Raised serum glucose (prediabetes, intermediate between above normal and diabetes)
- High serum triglycerides (but low HDL)
- Insulin resistance (you get high glucose and stimulate high insulin which doesn’t work as well)
Compare
Visceral (VS)/intra-abdominal fat to subcutaneous (SC) fat
Visceral fat is much worse, SC fat is more evenly distributed. This is more easily seen in women, with the apple vs pear shaped.
VS and SC fat express different developmental genes. The precise reasons why visceral fat isn’t really known, it may be because it drains easier into the liver.
What hormones are increased during food intake (the absorptive phase)?
What do the hormones do?
Insulin, Leptin, PPY, CCK, GLP-1.
These stimulate neurones in the hypothalamus which lead to an anorexigenic effect -> inhibits food intake/appetite suppressor.
What hormones are increased when the stomach is empty?
What do the hormones do?
When the stomach is empty, the hormone ghrelin released from the stomach will stimulate various neural pathways in the hypothalamus leading to an orexigenic effect -> stimulating food intake.
Ghrelin is a potent appetite stimulator.
Reducing leptin increases appetite.
