Adipokines and Obesity, Insulin Resistance
(in these notes IR = insulin resistance)
adipokine dysreg-->IR-->obesity or maybe so we think
players named: leptin, adiponectin, resistin
LEPTIN
the lean hormone
acts via hypothalamic receptors to reduce food intake, induce satiety
an insulin sensitizing agent
IR animals given leptin-->become insulin sensitive
being researched in humans
obese people have high levels and are resistant to it as well as insulin
explains how you can be hungry with a full belly
one large study suggests that consumption of lg amounts of fructose
-->leptin resistance and incr TGs in rats
MORE ON LEPTIN
helical peptide hormone
incr fat storage, decr appetite
incr energy expenditure via sympathetic activation of thermogenic tissue, kidneys and adrenals
incr pancreatic insulin secretion
increase related to puberty onset
incr in obesity suggests resistance, increased in OSA obstructive sleep apnea
modulates respiratory physiology, give leptin to animals-->better resp during sleep
incr plt agg
mb risk factor for vascular disease
ADIPONECTIN
protein hormone
affects glucose reg, fatty acid catabolism
improves insulin sensitivity-->
decreases gluconeogenesis
increases glucose uptake by adipocytes
also stabilizes endothelial responsiveness and may decr formation of antisclerotic plaques
statins mb anti-inflammatory via their effect on adiponectin
exclusively secreted from adipose into blood
serum levels inversely correlate with body fat percentage
so very fatty person: low adiponectin levels
RESISTIN
incr resistin and high insulin strongly correlated with obesity, IR and chronic inflam
incr resistin may occur in pts with chronic renal dz and decr renal fx, incr inflam, but without IR
appears to be pro-inflammatory cytokine that may mediate inflam dz regardless of IR
TZDs
thiazolidinediones
a class of antidiabetic compounds developed in 1980's as antioxidants
target receptor is PPARgamma (peroxisome proliferator-activated receptor gamma)
a nuclear receptor and transcription factor
several of the adipokines above hit the same receptor
turned on-->decr IR, turned off-->incr IR
PPARgamma is most highly expressed in adipose tissue
activation of the receptor by TZDs results in change in gene expression-->reduced insulin resistance
fat deposition downregs PPARgamma
SOURCES
Miller endocrinology notes 2011
...and some source that I read in Dr Peabody's office specifically about LEPTIN
adipokine dysreg-->IR-->obesity or maybe so we think
players named: leptin, adiponectin, resistin
LEPTIN
the lean hormone
acts via hypothalamic receptors to reduce food intake, induce satiety
an insulin sensitizing agent
IR animals given leptin-->become insulin sensitive
being researched in humans
obese people have high levels and are resistant to it as well as insulin
explains how you can be hungry with a full belly
one large study suggests that consumption of lg amounts of fructose
-->leptin resistance and incr TGs in rats
MORE ON LEPTIN
helical peptide hormone
incr fat storage, decr appetite
incr energy expenditure via sympathetic activation of thermogenic tissue, kidneys and adrenals
incr pancreatic insulin secretion
increase related to puberty onset
incr in obesity suggests resistance, increased in OSA obstructive sleep apnea
modulates respiratory physiology, give leptin to animals-->better resp during sleep
incr plt agg
mb risk factor for vascular disease
ADIPONECTIN
protein hormone
affects glucose reg, fatty acid catabolism
improves insulin sensitivity-->
decreases gluconeogenesis
increases glucose uptake by adipocytes
also stabilizes endothelial responsiveness and may decr formation of antisclerotic plaques
statins mb anti-inflammatory via their effect on adiponectin
exclusively secreted from adipose into blood
serum levels inversely correlate with body fat percentage
so very fatty person: low adiponectin levels
RESISTIN
incr resistin and high insulin strongly correlated with obesity, IR and chronic inflam
incr resistin may occur in pts with chronic renal dz and decr renal fx, incr inflam, but without IR
appears to be pro-inflammatory cytokine that may mediate inflam dz regardless of IR
TZDs
thiazolidinediones
a class of antidiabetic compounds developed in 1980's as antioxidants
target receptor is PPARgamma (peroxisome proliferator-activated receptor gamma)
a nuclear receptor and transcription factor
several of the adipokines above hit the same receptor
turned on-->decr IR, turned off-->incr IR
PPARgamma is most highly expressed in adipose tissue
activation of the receptor by TZDs results in change in gene expression-->reduced insulin resistance
fat deposition downregs PPARgamma
SOURCES
Miller endocrinology notes 2011
...and some source that I read in Dr Peabody's office specifically about LEPTIN