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ADIPONECTIN

BY: DR VARUN GUPTA


JR-2 DEPT. OF PHARMACOLOGY
RMCH BAREILLY
CONTENTS
• HISTORY
• INTRODUCTION
• ADIPONECTIN AS A HORMON
• WHY IS IT IMPORTANT TO STUDY ADIPONECTIN?
• CORRELATION BETWEEN ADIPONECTIN AND
INSULIN RESISTANCE
• ADIPONECTIN RECEPTORS
• DRUGS AFFECTING ADIPONECTIN LEVELS
• SUMMARY
HISTORY[1]
• Adiponectin was first identified in 1995 in
differentiating adipocytes.

• In 1996 it was identified in mice as the mRNA


transcript most highly expressed in adipocytes.

• In 2007, adiponectin was identified as a


transcript highly expressed in pre-adipocytes
(precursors of fat cells) differentiating into
adipocytes.
INTRODUCTION
• Adiponectin is a protein which in humans is
encoded by the ADIPOQ gene.[2]

• Composed of 247 amino acids.

• Accounts for 0.05 % of total serum protein.

• Concentration: 2- 20 μg/mL in the blood.

• adiponectin also gaining recognition as a


hormone.
ADIPONECTIN AS A HORMONE[3]
• Adiponectin is a white and brown adipose
tissue hormone.

circulates in the bloodstream in trimeric,


hexameric, and high-molecular-mass species.

Adiponectin is an insulin sensitizing hormone


that exerts its action through its receptors
AdipoR1, AdipoR2 & T-cadherin.
Contd..
• Adiponectin enhances AMPK (5' adenosine
monophosphate-activated protein kinase) [4] and the
PPARα [5] pathway in the liver and skeletal muscle.

• Adiponectin can exist in two different forms as-

1. a full-length protein or
2. as a globular form.

• The globular form of adiponectin appears to stimulate β


oxidation in muscle
• while the full-length form appears to decrease glucose
output by the liver
WHY IS IT IMPORTANT TO STUDY
ADIPONECTIN?
• Evidence strongly suggests that adiponectin
plays a role in the pathophysiology of type 2
diabetes and other metabolic syndrome
diseases!!


CORRELATION BETWEEN ADIPONECTIN
AND INSULIN RESISTANCE
• Obesity and type 2 diabetes are associated with
decreased adiponectin levels
• Reduced plasma adiponectin is also seen in people
with conditions such as cardiovascular disease and
hypertension, diseases that are often associated with
insulin resistance.
• In a study conducted by Hotta et al., (2001), plasma
adiponectin levels dropped in parallel to the
observation of decreased insulin sensitivity in rhesus
monkeys. [6]
• Monkeys with decreased insulin sensitivity developed
type 2 diabetes.[6]
Contd..
• Adiponectin is inversely proportional to
obesity, diabetes, and other insulin-resistant
states.[7]

• Plasma concentrations reveal a dimorphism,


with females having higher levels than males.

• Weight reduction significantly increases


circulating levels.
Contd.
• Adiponectin increases fatty acids oxidation, which lowers
circulating free fatty acids and prevents insulin resistance. [7]

• Adiponectin has been reported to exert an antiatherosclerotic


effect. [8]
• It inhibits macrophage activation and foam cell accumulation,
while it also augments endothelial nitrous oxide production
and protects the vasculature by reducing platelet aggregation
and vasodilation.

• Apart from causing metabolic dysfunction, adiponectin


deficiency may also contribute to coronary heart disease,
insulin resistance, nonalcoholic fatty liver disease.[9]
Contd..
• The physiological role of
adiponectin has not yet been fully
elucidated, but it is believed that
it has the ability to reduce
glucose, triglycerides, and free
fatty acids.

• it plays a major role in the


pathogenesis of metabolic
syndrome.

• Metabolic syndrome comprises a


cluster of metabolic disorders
that give rise to such metabolic
risk factors [10]

• Such as visceral obesity, insulin


resistance, hyperglycaemia
,dyslipidaemia, and hypertension
ADIPONECTIN RECEPTORS [12]
• There are two known ones: AdipoR1 and AdipoR2 & T-
cadherin.

• They are integral membrane proteins that have seven


transmembrane domains where the N terminus is
located within the cell, and the C terminus is external.

• AdipoR1 is a receptor that mainly binds globular


adiponectin, while AdipoR2 binds to full-length
adiponectin

• AdipoR1 is abundant in skeletal muscle. On the other


hand, AdipoR2 is most expressed in the liver.
RECEPTOR
• T-cadherin can bind to the hexameric and
HMW forms of adiponectin but not to
monomer globular and trimeric forms.

• T-cadherin is ubiquitously expressed, with the


highest expression found in the heart and the
aortic, carotid, iliac, and kidney arteries.
Osmotin [13]
• potential agonist for adiponectin!!
• It is a plant protein that is implicated in the
plant defense system. Causes apoptosis in
yeast.
• adiponectin and osmotin were able to induce
phosphorylation of AMP kinase in C2C12
myocytes.
DRUGS AFFECTING ADIPONECTIN LEVELS

• Thiazolidinediones [14] increases adiponectin


levels in all subjects, including normal subjects in
which no other effects of TZDs are observed.
• Insulin also appears to suppress adiponectin
levels.

• Disease-modifying antirheumatic drugs(DMARDs)


[15] increase serum adiponectin levels in patients
with rheumatoid arthritis.
SUMMARY
1. adiponectin is a potent insulin sensitizing
molecule.
2. The two forms (globular and full-length) bind to
different receptors and have different effects.
3. Decreased levels of adiponectin induced by
genetic mutations, obesity, and high fat diets
lead to insulin resistance and pathological
conditions such as type 2 diabetes.
4. Adiponectin activates signaling cascades that
eventually increase glucose uptake by muslce,
increase fatty acid oxidation by muscle and liver,
and decrease gluconeogenesis in the liver.
5. In the future, Osmotin could be used as a novel
therapeutic method for hypoadiponectinemia.
Adiponectin as a hormone refrence
• HORMONES 2012, 11(1):8-20
• DOI:
• Review
• Adiponectin: Regulation of its production and its role in human diseases
• Adeeb Shehzad,1 Waqas Iqbal,1 Omer Shehzad,2 Young Sup Lee1
• 1School of Life Sciences, College of Natural Sciences, Kyungpook National University, Daegu, 2Natural Products Research Institute,

College of Pharmacy, Seoul National University, Seoul, Korea


• Abstract
• Adiponectin is a white and brown adipose tissue hormone, also known as gelatin-binding protein-28 (GBP28), AdipoQ, adipocyte
complement-related protein (ACRP30), or apM1. Adiponectin circulates in the bloodstream in trimeric, hexameric, and high-molecular-
mass species, while different forms of adiponectin have been found to play distinct roles in the balance of energy homoeostasis.
Adiponectin is an insulin sensitizing hormone that exerts its action through its receptors AdipoR1, AdipoR2, and T-cadherin.
AdipoR1 is expressed abundantly in muscle, whereas AdipoR2 is predominantly expressed in the liver. Adiponectin is inversely
proportional to obesity, diabetes, and other insulin-resistant states. In this review we present the current findings regarding the
regulation of its production and several new findings pertaining to its biological effects. Adiponectin enhances AMPK and the PPARα
pathway in the liver and skeletal muscle. Adiponectin increases fatty acids oxidation, which lowers circulating free fatty acids and
prevents insulin resistance. Adiponectin has been reported to exert an antiatherosclerotic effect. It inhibits macrophage activation and
foam cell accumulation, while it also augments endothelial nitrous oxide production and protects the vasculature by reducing platelet
aggregation and vasodilation. Apart from causing metabolic dysfunction, adiponectin deficiency may also contribute to coronary heart
disease, steatohepatitis, insulin resistance, nonalcoholic fatty liver disease, and a wide array of cancers. In this study, we present ample
evidence that adiponectin mediates multiple molecular pathways. We therefore support the concept that it shows distinct potential for
being of therapeutic value in the treatment of obesity related diseases, ranging from metabolic syndrome to malignancies.
• Keywords
• Adiponectin, Regulation, Insulin, Inflammation, Atherosclerosis, Fatty acid, Obesity, Liver disease
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The effect of thiazolidinediones on plasma adiponectin
levels in normal, obese, and type 2 diabetic subjects.
Yu JG1, Javorschi S, Hevener AL, Kruszynska YT, Norman RA,
Sinha M, Olefsky JM.
• 15. J Clin Rheumatol. 2011 Jan;17(1):14-7. doi:
10.1097/RHU.0b013e318204a587.
• Disease-modifying antirheumatic drugs increase serum
adiponectin levels in patients with rheumatoid arthritis.
• Cansu B1, Cansu DU, Kaşifoğlu T, Gülbas Z, Korkmaz C.
• Author information
• Abstract
• BACKGROUND:
• Adiponectin is an adipocyte-derived adipokine with
immunosuppressive and anti-inflammatory properties. It also
decreases expression of adhesion molecules. In terms of its
relationship with acute-phase reactants, there are conflicting
results in patients with rheumatoid arthritis (RA).
Thank you