Adipose tissue as an endocrine organ

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3. o Adipose tissue:
• White adipose tissue (WAT): stores energy
• Brown adipose tissue (BAT: generates body heat
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4. WAT vs BAT
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5. The most significant physiological functions of WAT
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6. Adipose tissue as an endocrine organ
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7. o Discovery in 1994.
o Derived from the Greek word “λεπτός” )Leptos( meaning “thin“.
o A small peptide (16 kDa) with 167 amino acids.
o Is expressed by the LEP gene, )also known as the ob(.
o Ob gene (Ob for obese) is located on chromosome 7q31.
o Is expressed mainly by adipose tissue, but also found in the
skeletal muscle, gastric and mammary epithelium and the
brain.
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8. o Is increased by:
 Food intake, insulin, glucocorticoids and proinflammatory
cytokines.
o Is decreased by:
 Fasting, cold exposure, exercise, adrenergic stimulation,
growth hormone, thyroid hormone, melatonin, smoking,
thiazolidinediones and with increasing age. 8

9. o Its levels are higher in females than males, partly as a result
of:
 Inhibition by androgens, stimulation by estrogen.
 Females have a higher proportion of subcutaneous fat
(Leptin synthesis is greater in subcutaneous than in visceral
adipose tissue).
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o Signals to the brain about body fat stores.
o Regulation of appetite and energy expenditure.
o And wide variety of physiological functions:
• Modulation of the reward circuitry for feeding, glucose metabolism,
lipid oxidation, substrate partitioning, and adipocyte apoptosis.

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o Mutation in the:
 Leptin gene (ob / ob)
or
 Leptin receptor (db / db)
Obesity

13. o Serum leptin concentrations show a moderate circadian
variation:
A peak during the night at 02:00.
 The leptin concentrations at this time are 30–100% higher than in the
morning or early afternoon.
o There is no alteration in measured leptin concentrations in samples
stored at 20 °C over a 2-year period.
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14. o Radioimmunoassay (RIA) and ELISA procedures:
o suitable for the measurement of leptin in fluids plasma or in serum from
patients with anorexia nervosa, which have much lower leptin concentrations.
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16. o Also known as:
 AdipoQ,
 Gelatin-Binding Protein of 28 kDa (GBP28),
 Adipose most abundant gene transcript 1 (apM1),
 Adipocyte Complement-Related Protein of 30 kDa (ACRP30).
o Is a protein hormone with 244 amino acids.
o The adiponectin gene on chromosome 3q27 was described in 1995.
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17. o This adipokine circulates in three isoforms:
 A trimer, low molecular weight (LMW),
 A hexamer (trimer-dimer) of medium molecular weight (MMW),
 A multimeric high molecular weight of (HMW).
o Circulating adiponectin concentrations are high (500 –30000
μg/L).
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18. o Adiponectin exists as a:
o full-length Adiponectin (fAdp):
 Mw=30 kDa
 Circulates in trimeric, hexameric and higher order complexes.
o globular Adiponectin (gAdp):
 A fragment containing the globular domain of adiponectin
which has potent metabolic effects in various tissues.
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19. o They contain 7 transmembrane domains:
Adipo R1:
 Is expressed mainly in skeletal muscle but also found in the
hypothalamus, liver and other tissues.
 Works with high affinity with gAdp and low affinity with
fAdp.
Adipo R2:
 Is expressed primarily in the liver, but is also found in skeletal
muscle and white adipose tissue. 19

20. o Is involved in regulating glucose levels and fatty acid breakdown.
o May play anti-atherogenic and anti-inflammatory roles.
 Plasma adiponectin concentrations are decreased in patients with CAD.
 It is conceivable that the use of recombinant adiponectin may become
beneficial in the prevention of cardiovascular disease.
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22. o Negatively correlates with:
 Obesity,
 BMI,
 Percentage of body fat,
 Fasting insulin concentration,
 Coronary artery disease,
 Type II diabetes,
 plasma triglycerides.
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o Positively correlates with:
 HDL-C,
 Type I diabetes,
 Anorexia nervosa

23. o TNFα produced by WAT in obesity and suppresses adiponectin.
o Thiazolidinediones prevent this inhibitory effect of TNFα.
o Both insulin and IGF-1 increase adiponectin synthesis in WAT.
o Serum adiponectin concentrations were high in thin individuals and low in
obese individuals.
o Moreover, surgical treatment of morbid obesity by gastric partition surgery
leads to an increase in plasma adiponectin concentration, which is
significantly correlated with body weight reduction.
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24. o Competitive RIAs and sandwich ELISAs:
 RIA has a lower limit of detection of 1 μg/L.
 ELISA has lower limits of detection of 0.079 –0.891 μg/L.
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25. o Discovered in 2001.
o Is called “resistin”: because of insulin resistance in mice injected
with resistin.
o Is a 12.5-kDa protein, contains 108 amino acids.
o Contains high quantities of cysteine.
o Is encoded by the RETN gene.
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26. o Is secreted not only by adipocytes, but also by a large number of
cells, in particular immunocompetent cells.
o Circulates in human blood as a dimeric protein consisting of two
92 amino acid polypeptides that are linked by a disulfide bridge
at Cys-26.
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27. o Release of resistin stimulated by:
 Inflammation,
 LPS (Lipopolysaccharide),
 Il-6,
 TNF α,
 Hyperglycemia,
 Growth and gonadal hormones.
o Thiazoladinedione drugs suppress the production of resistin.
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28. o Very little is known about the potential function of resistin.
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29. o There is no correlation between resistin mRNA expression and:
 Body weight,
 Obesity,
 Insulin resistance.
o Resistin concentrations in persons with type 2 diabetes do not
differ from concentrations in the general population .
o Plasma resistin concentrations are decreased in anorectic patients.
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30. o Was first described in 2005.
o Is a 52 kDa protein with 491 amino acids.
o Also known as:
 pre-B-cell colony-enhancing factor 1(PBEF1),
 Nicotinamide phosphoribosyltransferase (NAmPRTase or Nampt).
o Is encoded by the NAMPT gene.
o Is principally produced by visceral adipose tissue, so is called visfatin.
o Also produced by macrophages of the visceral adipose tissue, and in small
quantities by subcutaneous adipose tissue. 30

31. o Nampt is a rate-limiting enzyme in the NAD+ salvage pathway that
converts nicotinamide to nicotinamide mononucleotide (NMN).
o APO866 is an experimental drug that inhibits this enzyme.
 It is being tested for treatment of advanced melanoma, cutaneous T-cell
lymphoma (CTL), and refractory or relapsed B-chronic lymphocytic
leukemia.
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32. o Visfatin (PBEF):
 Promotes B cell maturation and inhibits neutrophil apoptosis.
 Plays an important role in the progression of arthritis.
 Induces the production of IL-1, IL-6 and TNF-α.
o Visfatin can therefore be referred to as a cytokine because its
plasma level increases in inflammatory conditions such as
psoriasis, arthritis and obesity.
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33. o Visfatin have insulino-mimetic action:
 Because it bind insulin receptors at a site that differs from
that of insulin and reduces blood glucose level.
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35. o There is a positive correlation between obesity and visfatin.
o Visfatin was significantly elevated in the serum of type 2 DM
patient compared to controls.
o Visfatin plasma levels significantly correlates to BMI.
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36. o Is a novel hydrophilic adipokine of 313 amino acids (35 kDa).
o It was initially identified in intestinal Paneth cells and endothelial
cells with the name Intelectin-1.
o In 2005, omentin was officially depicted in an omental fat.
o Omentin-1 and omentin-2 are two highly homologous isoforms.
 Omentin-1 is the major circulating form with a concentration of 100 ng/mL
to 1 g/mL in human plasma.
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37. o Are inversely related to obesity and positively to adiponectin levels.
o Serum levels of omentin were low in patients with:
 Impaired glucose regulation
 T2DM
 Polycystic ovary syndrome (PCOS)
 Atherosclerosis
 Coronary artery disease (CAD)
 Heart failure
 Psoriasis
 Rheumatoid arthritis.
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38. o Omentin levels were elevated in:
 Nonalcoholic fatty liver disease (NAFLD)
 Hepatic carcinoma
 Prostate cancer
 Colon and colorectal cancer
 Gastric cancer
 And pancreatic adenocarcinoma
o Omentin may have an anti-cancer effects. 38

39. o Omentin can regulate:
Inflammation status
Vasomotor and endothelium function
Proliferation
Apoptosis
Differentiation of cell types.
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40. Adipose tissue is the primary storage site for excess energy but
it is also recognized as an endocrine organ. Adipocytes
are now generally accepted to be a complex cell type
involved in generating a number of signals which include
cytokines, hormones and growth factors that not only
affect the neighboring cells but also impact target tissues
involved in energy metabolism and influencing physiologic and
pathologic processes.
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44. o Endocrine Regulation of Energy Metabolism: Review of Pathobiochemical and
Clinical Chemical Aspects of Leptin, Ghrelin, Adiponectin, and Resistin.
DOI: 10.1373/clinchem.2004.032482
o Biochemistry of adipose tissue: an endocrine organ. DOI:
10.5114/aoms.2013.33181.
o Visfatin: Structure, Function and Relation to Diabetes Mellitus and Other
Dysfunctions. https://doi.org/10.2174/092986708785133004.
o Omentin-A Novel Adipokine in Respiratory Diseases. doi:10.3390/ijms19010073
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