adipocytes and insulin resistance Flashcards
major regulator of adipocyte functioning in fed state
STORAGE
- insulin
- increased uptake of glucose into adipocytes to be used for glycerol and also increases activity of LPL to liberate free FA so they can enter adipocytes
regulation of adipocytes in fasted state or when metabolic demand is high
LIPOLYSIS
- epinephrine/glucagon
- stimulate cAMP –> PKA –> phosphorylates hormone sensitive lipase
what is the action of hormone sensitive lipase?
involved in removing FA from triglycerides, most affinity for DAG
outline the reactions from TAG to glycerol + FA in adipose cells
TAG = DAG + FA by desnutrin and HSL DAG = MAG + FA by HSL MAG = glycerol + FA by MAG lipase
describe partitioning of free fatty acids in the fed state
in the fed state, FFA that are liberated by LPL are trapped in local adipose tissue so that they are not taken up by cells that are not needing additional energy
describe the use of fatty acids in the fasted state
in the fasted state, insulin levels are low and thus epinephrine’s activation of HSL is unopposed. this results in the release of FFA that travel to the liver and are used for ketogenesis or gluconeogenesis
why are upper body adipocytes assoc with increased risk of CVD?
upper body adipocytes are larger and larger size = more cytokines and more inflammation
describe leptin
adipokine secreted by adipose tissues that acts as a regulator of food intake on the arcuate nucleus of the hypothalamus
what inhibits leptin transcription?
PPARg
in most cases of polygenic obesity, leptin levels are actually high, why?
leptin levels are high because there is a defect in the signaling pathway (JAK/STAT) - thus “leptin resistance” develops and supplementation does not help
central action of leptin (1)
reduce triglyceride content in adipose and non-adipose tissues
peripheral actions of leptin (3)
- stimulate lipolysis
- reduce expression of acetyl-CoA carboxylase
- inhibit lipogenesis with inhibition of SREBP-1
current view of leptin
signal of energy sufficiency
what is the overall action of adipsin?
promotes triglyceride storage in adipocytes and reduce accumulation in liver and muscle
which adipokine has “positive effects”?
adiponectin= anti-diabetic, anti-inflammatory, anti-atherogenic
what is the effect of adiponectin in skeletal mm?
increases FA oxidation
what is the effect of adiponectin in liver?
- decreases FA influx
- decreased gluose output
- increases FA oxidation
what are the correlations between plasma levels and adiponectin?
inverse correlation with triglyceride levels
direct correlation with HDL levels
effects of TNFa on adipocytes (3)
- destabilizes lipid droplets to make triglycerides accessible to HSL
- through NFkB, decreases expression of adipogenic and lipogenic genes
- inhibits LPL synthesis
effects of TNFa on liver
- increases exp of genes for fatty acid synthesis
- decreases exp of genes for fatty acid oxidation
why are visceral adipose depots associated with more bad effects?
hormones secreted from visceral fat can reach liver directly through portal circulation, ask express more IL-6 and PAI-1 = increased inflammation and thrombosis
what 2 adipokines are secreted more by subcutaneous fat?
leptin and adiponectin
what are PPARs and how do they work?
PPARs are transcription factors involved in adipocyte differentiation and metabolism; form heterodimers with RXRs and bind to PPRE in promoter to regulate transcription
ligands for the different isoforms
PPARa- fibrates
PPARg- TZDs
PPARd- fatty acids
