BMW3010 – Multimorbiditeit in Obesitas – Case 1
, BMW3010 – Multimorbiditeit in Obesitas – Case 1
1. DEEP INTO LIPID METABOLISM
Storage
TAG come either from very-low-density lipoproteins secreted by the liver or, after eating,
from chylomicrons that transport TAG reconstituted form the digestion products of
dietary fats. (see learning goal 2 for storage and regulation)
Mobilization
Mobilization of fatty acids involves the process of lipolysis. During lipolysis, intracellular
TAG is sequentially hydrolyzed into diacylglycerol (adipose triglyceride lipase, ATGL),
monoacylglycerol (hormone-sensitive lipase, HSL), and glycerol (MAG lipase, MGL),
releasing one molecule of FA at each step. FFA and glycerol efflux from fat cells is followed
by transport of these metabolites in the blood stream (liver – glycerol; skeletal muscle,
liver, heart – FFAs). Lipolysis is influenced by several regulators:
Catecholamines (noradrenaline + adrenaline)
Natriuretic peptides
Insulin (also potential antilipolytic action via hypothalamic control)
Cortisol
The regulators work via activation or inhibition of plasma membrane adenylyl cyclase
activity, via receptors from the G-protein-coupled receptor family – the adenylyl cyclase
activity controls the formation of cyclic adenosine monophosphate (cAMP) from ATP:
Increase in intracellular cAMP – enhances protein kinase A (PKA) activity
stimulates lipolysis
Decrease in intracellular cAMP inhibits lipolysis
Catecholamines stimulate lipolysis trough the activation of beta-adrenergic receptors
(β1 and β2) increase in cAMP levels. However, catecholamines are also able to stimulate
an antilipolytic pathway involving α2-adrenergic receptors. There are many more
molecules and receptors involved in the inhibition of lipolysis through GI(inhibitory)-
protein-coupled receptors, which do not only originate from adipocytes, but also from
endothelial cells, macrophages, pre-adipocytes and sympathetic nerve terminals.
, BMW3010 – Multimorbiditeit in Obesitas – Case 1
1. DEEP INTO LIPID METABOLISM
Storage
TAG come either from very-low-density lipoproteins secreted by the liver or, after eating,
from chylomicrons that transport TAG reconstituted form the digestion products of
dietary fats. (see learning goal 2 for storage and regulation)
Mobilization
Mobilization of fatty acids involves the process of lipolysis. During lipolysis, intracellular
TAG is sequentially hydrolyzed into diacylglycerol (adipose triglyceride lipase, ATGL),
monoacylglycerol (hormone-sensitive lipase, HSL), and glycerol (MAG lipase, MGL),
releasing one molecule of FA at each step. FFA and glycerol efflux from fat cells is followed
by transport of these metabolites in the blood stream (liver – glycerol; skeletal muscle,
liver, heart – FFAs). Lipolysis is influenced by several regulators:
Catecholamines (noradrenaline + adrenaline)
Natriuretic peptides
Insulin (also potential antilipolytic action via hypothalamic control)
Cortisol
The regulators work via activation or inhibition of plasma membrane adenylyl cyclase
activity, via receptors from the G-protein-coupled receptor family – the adenylyl cyclase
activity controls the formation of cyclic adenosine monophosphate (cAMP) from ATP:
Increase in intracellular cAMP – enhances protein kinase A (PKA) activity
stimulates lipolysis
Decrease in intracellular cAMP inhibits lipolysis
Catecholamines stimulate lipolysis trough the activation of beta-adrenergic receptors
(β1 and β2) increase in cAMP levels. However, catecholamines are also able to stimulate
an antilipolytic pathway involving α2-adrenergic receptors. There are many more
molecules and receptors involved in the inhibition of lipolysis through GI(inhibitory)-
protein-coupled receptors, which do not only originate from adipocytes, but also from
endothelial cells, macrophages, pre-adipocytes and sympathetic nerve terminals.
