Adipokines

PRESENTOR : Dr. KAPIL

MODERATOR: Dr. BD BANERJEE

DEFINITION Adipose tissue is now recognized as an endocrine

organ capable of secreting a variety of biologically active components which are called adipokines.

Adipokines affect appetite and satiety, glucose and lipid metabolism, blood pressure regulation, inflammation and immune functions.

ADIPOKINES Leptin

Adiponectin

Resistin

Adipsin

Apelin

Visfatin

Vaspin

Omentin

Lipocalin-2

LEPTIN Leptin is a 16 kDa non glycosylated peptide

hormone encoded by the gene obese(ob)

Circulating leptin levels are directly correlated with adipose tissue mass

Leptin is secreted in a pulsatile fashion and has significant diurnal variation with higher levels in the evening and early morning hours.

FUNCTIONS The primary actions originally described for leptin are

mediated via binding to Ob-R in the brain, resulting in suppression of appeite and increased energy expenditure.

Appetite suppression is mediated via binding of leptin to its full length receptor (Ob-Rb)in the hypothalamic satiety centres, with stumulation of anorexigenic/catabolic neurons and suppression of orexigenic/anabolic neurons

LEPTIN RECEPTOR

LEPTIN-MECHANISM OF ACTION

OTHER PERIPHERAL FUNCTIONS: LEPTIN AND HAEMATOPIESIS

Ob-R is expressed in haemopoietic cells and leptin is linked to proliferation and differentiation of haemopoietic precursors.

High concentration of human leptin promote platelet aggregation

LEPTIN-ANGIOGENESIS Leptin receptors are expressed in human vasculature

Stimulates endothelial cell growth and angiogenesis

So topical application of leptin also induces dose dependent acceleration in wound repair

LEPTIN AND REPRODUCTION: Expression of Ob-R has also been demonstrated in

human granulosa cells

Significant increase in circulating leptin levels cause ovarian hyper stimulation suggesting that leptin plays a role in follicular growth and maturation

PLACENTAL LEPTIN Placental leptin is likely to affect maternal, placental

and fetal function through both autocrine and paracrine mechanisms.

Placental leptin has physiological affects on the placenta including angiogenesis, growth and immunomodulation

LEPTIN IN FERTILITY Studies have shown that leptin treated females had

significantly elevated serum levels of LH, increased ovarian and uterian weight

And leptin treated males had significantly elevated serum levels of FSH, increased testicular and seminal vesicle weights, greater seminal vesicle epithelial width and elevated sperm counts.

LEPTIN IN PREGNANCY Serum leptin is particularly elevated during second

and third trimesters.

Uterine contractions are inhibited by leptin

Leptin plays a role in hyperemesis gravidarum

LEPTIN IN PUBERTY Leptin may act on hypothalamic cells to stimulate

release of LHRH, thereby triggering gonadotropinrelease.

The subsequent release of follicle stimulating hormone and LH stimulates gonadal steroid secretion, leading to development of the reproductive tract and induction of puberty.

LEPTIN AND INSULIN Hyperinsulinemia is associated with increased plasma

leptin concentration.

Insulin appears to act directly at the level of adipocyteby increasing leptin secretion and gene expression

ROLE OF LEPTIN IN OSTEOARTHRITIS

ADIPONECTIN Adiponectin appears to be a second well known

adipocytokine released by fat cells.

Adiponectin (also known as 30-kDa adipocytecomplement-related protein; Acrp30) is a 247 amino-acid protein monomer which forms trimers which further polymerize into larger polymeric complexes varying in size between 180kDa (hexameres; LMW) or 400-600kDa (16-meres; HMW) .

DIFFERENT MOLECULAR FORMS

ADIPONECTIN RECEPTORS

FUNCTIONS: Enhancement of insulin sensitivity

Anti-inflammatory properties

Inhibition of the development of atherosclerosis

MOLECULAR MECHANISM

INSULIN SENSITIZING ACTION

ADIPONECTIN IN ATHEROSLEROSIS

RESISTIN:• Resistin is a dimeric protein containing 108 amino acids

that received its name from its apparent induction of insulin resistance in mice.

• It belongs to the found in inflammatory zones

(FIZZ) family (also known as RELMs, resistin-like

molecules).

Resistin (FIZZ3) has been found in

adipocytes, macrophages, and other cell types.

FUNCTIONS: Induces severe hepatic insulin resistance

Resistin has been reported to inhibit dopamine and nor adrenaline release in the hypothalamus

ADEPSIN: Also called human complement factor D

(enzyme in the alternative pathway of complement activation)

Functions:

Stimulates triglyceride storage,

enhances fatty acid reesterification and inhibits lipolysis

APELIN A bioactive peptide, secreted mainly from adipocytes

and stromal vascular cells

Functions:

Inhibits glucose induced insulin secretion;

inducing NO production and inhibiting angiotensin II cellular signaling.

VISFATIN An insulin mimetic adipokine recently discovered and

released prevalently by visceral WAT

Visfatin is also identical to pre-B-cell colony enhancing factor

Under endotoxin stimulation it is also produced by neutrophils

FUNCTIONS: Hypoglycemic effect by stimulating glucose uptake, promotes insulin sensitivity;alsoinduces chemotaxis.

VASPIN visceral adipose tissue-derived serine protease

inhibitor

Serine protease inhibitor

FUNCTIONS:

Improves insulin sensitivity.

suppresses the production of resistin, leptin and TNF-α

OMENTIN A secretory protein ,recently identified a new

adipokine.

FUNCTIONS:

Enhances insulin stimulated glucose transport in subcutaneous as well as omental adipocytes.

LIPOCALIN-2 It is also known as neutrophil gelatinase associated

lipocalin

It is a 25kDa secretory glycoprotein, originally identified in mouse kidney cells and human neutrophil granules.

FUNCTIONS:

seems to have dual effects on inflammation, pro & anti-inflammatory effects.

So increased levels of LCN2 in obesity and IR may constitute a protective mechanism against inflammation.

Thank you