Lecture notes
Adipokines
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- Aston University, Birmingham (Aston)
In depth cell signalling and physiology notes, created using synchronous and asynchronous material.
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Adipokines.Introduction to adipokines.
What is obesity.
• The World Health Organization defines obesity as “abnormal or excessive fat
accumulation that presents a risk to health.”
• We use BMI as a definition of obesity. This is your weight in KG divided by you
meters squared.
• This is an unhelpful way to measure obesity as it does not tell you about body
composition or muscles.
• Better to use body fat percentage as a measure of obesity.
• Adipokines come from body fat.
• Circulating levels of adipokines change as we gain or loose weight.
Adipose tissue.
• There are different types of adipose tissue.
• White adipose tissue: this is fat you see around the middle of the body
• Brown adipose tissue: very small amounts.
• Beige adipose tissue: these are white adipocytes that have been chemically driven
towards a brown pathway.
• Adipose tissue is a form of connective tissue, and there is an extracellular matrix that
surrounds it.
• Adipose tissue is not made of just adipocytes (fat cells), adipokines come from
adipose tissue but not necessarily adipocytes, they can come from the other cells
that are there.
• Adipose tissue is made up of adipocytes, stromal vascular cells, (these are cells that
can form blood vessels), pre- adipocytes (these are cells that can differentiate into
adipocytes), fibroblasts, endothelial cells and monocytes and macrophages, these
are important as they can release the inflammatory related adipokines.
• Adipose tissue is needed to store energy, so if we went through a period of famine, it
would provide us with an energy source for months.
• It provides a cushion for our organs, the fat helps to pad the muscles and bones and
this is also useful for insulation, to prevent heat loss.
•
Adipokines.
• Adipose tissue was traditionally thought to insulate, protect from injury and store
energy for fasts.
• However, in 1994 there was a study on the obese mouse, which does not stop
eating. It is an animal model of type 2 diabetes, because these mice eat so much
they become insulin resistant and then their pancreas stops being able to produce
insulin. The first of these mice arose by chance, by a mutation.
• It was not understood why this mouse would not stop eating, it was found that there
was an autosomal recessive mutation in a gene, this causes them to gain weight
rapidly after a couple of weeks.
, • This was a mutation in the adipokine, which meant the mouse could not stop eating
and got obese.
• Adipokine is a hormone which moves from adipocytes.
• Adipokines refers to cytokines, acute phase reactants, growth factors and other
inflammatory mediators and adipose tissue hormones, such as leptin and other
chemical messengers.
• Adipokines have autocrine effects (they can affect the adipocyte or other cells in
adipose tissue that they are released from), they also have paracrine effects and
endocrine mechanisms of action they can travel throughout the body having impacts
in the brain, which is where leptin, has its normal physiological effects.
• Many adipokines effect processes in both the periphery and CNS.
major adipokine classes
We can class adipokines based on what they do.
1. Metabolic adipokines- factors that have an impact on metabolism.
2. Pro-inflammatory adipokines- factors which will drive an inflammatory process.
3. ECM components
4. Mitogenic/angiogenic adipokines- factors which drive cell proliferation or the
production of new blood vessels.
• Metabolic adipokines:
• Adiponectin
• Leptin
• visfatin
• Pro-inflammatory adipokines (2)
• TNF-α
• Interleukins (1β, 4, 6, 8 and 18)
• Macrophage migration inhibitory factor (MIF)
• Visfatin (this is pro inflammatory as well as metabolic this shows that adipokines can
fit into more than one category.)
• Macrophage chemoattractant protein-1 (MCP1)
• Extracellular matrix (ECM) components (3)
• Collagen I, III, IV and VI
• Matrix metalloproteinases (MMPs) 1, 7, 9, 10, 11, 14 and 15
• Fibronectin
• In long term obesity the extracellular matrix builds up around the adipocytes, and
thickens, it undergoes a process known as fibrosis, this causes adipokines to get a
little bit smaller.
• Mitogenic/angiogenic adipokines: (4)
• Insulin-like growth factor 1 IGF1)
• Fibroblast growth factor (FGF)
• Hepatocyte growth factor (HGF)
• Transforming growth factor beta (TGFβ)
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