Wednesday, May 8, 2013

Leptin

Leptin

The discovery of leptin more than a decade ago was a major turning point in our understanding
of adipokines. Mice and humans homozygous for the leptin gene mutation
develop hyperphagia, severe early-onset obesity, insulin resistance preceding obesity,
excess lipid accumulation outside adipose tissue (steatosis), and neuroendocrine abnormalities,
notably, hypothalamic hypogonadism and tertiary hypothyroidism.
Moreover, there is evidence for immunosuppression in congenital leptin deficiency. Leptin is expressed and secreted mainly by adipocytes, but low levels are present in the gastric fundus, mammary gland, placenta, pituitary and skeletal muscle. Leptin has a relative molecular mass of 16kDa and circulates in free or bound forms. The latter represents leptin bound mainly to its soluble receptor and is thought
to be inactive. The concentration of leptin is higher in obese than lean individuals.
Leptin falls rapidly during fasting and increases gradually during feeding. Studies in
rodents and human indicate a link between these changes in leptin and insulin.
Higher leptin level in women is explained partly by increased production in subcutaneous
adipose tissue and stimulation by estrogens. On the other hand, leptin is suppressed
by androgens in males. Chronic glucocorticoid exposure, TNF- and IL-6
increase leptin, while adrenergic stimulation decreases leptin. Leptin exhibits a
diurnal rhythm, peaking at night in humans and in the morning in rodents.
A pulsatile leptin rhythm has also been recognized in humans, although the underlying
mechanisms and functional significance are unknown.
Five leptin receptor isoforms, LRa–LRe, are derived from alternate splicing of lepr
mRNA. LRa is the predominant ‘short leptin receptor’ which lacks the key
cytoplasmic domain required for signaling through the JAK/STAT (signal transduction
and activators of transcription) pathway. LRa is abundantly present in brain capillary
endothelium and peripheral tissues, and is thought to mediate leptin transport.

0 yorum:

Post a Comment