Nesfatin-1

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Nesfatin-1 is a neuropeptide produced in the hypothalamus of mammals. It participates in the regulation of hunger and fat storage.[1] Increased nesfatin-1 in the hypothalamus contributes to diminished hunger, a 'sense of fullness', and a potential loss of body fat and weight.

A study of metabolic effects of nesfatin-1 in rats was done in which subjects administered nesfatin-1 ate less, used more stored fat and became more active. Nesfatin-1-induced inhibition of feeding may be mediated through the inhibition of

orexigenic neurons.[2] In addition, the protein stimulated insulin secretion from the pancreatic beta cells of both rats and mice.[3]

Biochemistry

Nesfatin-1 is a

NUCB2
). Recombinant human Nesfatin-1 is a 9.7 kDa protein containing 82 amino acid residues.[4] Nesfatin-1 is expressed in the hypothalamus, in other areas of the brain, and in pancreatic islets, gastric endocrine cells and adipocytes.

Satiety

Nesfatin/NUCB2 is expressed in the appetite-control

nucleus of the solitary tract (NTS) and Dorsal nucleus of vagus nerve
.

Brain

Nesfatin-1 can cross the blood–brain barrier without saturation.[5]

The

cannabinoid receptors. Nesfatin-1-induced inhibition of feeding may be mediated through the inhibition of orexigenic NPY
neurons.

Nesfatin/NUCB2 expression has been reported to be modulated by starvation and re-feeding in the

postprandial regulation of feeding behavior and energy homeostasis.[6][7]

Nesfatin-1 immunopositive neurons are also located in the

orexigenic
effect of peripherally administered ghrelin in freely fed rat.

Nesfatin-1 was co-expressed with

tuberal hypothalamic neurons. Nesfatin-1 co-expressed in MCH neurons may play a complex role not only in the regulation of food intake, but also in other essential integrative brain functions involving MCH signaling, ranging from autonomic regulation, stress, mood, cognition to sleep.[8]

Metabolism

There is growing evidence that nesfatin-1 may play an important role in the regulation of food intake and

type 2 diabetes mellitus (T2DM) and associated with BMI, plasma insulin, and the homeostasis model assessment of insulin resistance.[10][11]

It was found that central nesfatin-1 resulted in a marked suppression of hepatic

mRNA and protein levels in both standard diet (SD) and high fat diet (HFD) rats but failed to alter glucose 6-phosphatase (G-6-Pase) activity and protein expression. Central nesfatin-1 appeared to antagonize the effect of HFD on increasing PEPCK gene expression in vivo. In agreement with decreasing PEPCK gene expression, central nesfatin-1 also resulted in a reduced PEPCK enzyme activity, further confirming that it affected PEPCK rather than G-6-Pase.[11]

The part of the glucose entering the

hepatic PEPCK protein and activity, but failed to alter hepatic G-6-Pase activity, suggesting that PEPCK may be more sensitive to short-term central nesfatin-1 exposure than G-6-Pase. In addition, suppression of HGP by central nesfatin-1 was dependent on an inhibition of the substrate flux through G-6-Pase and not on a decrease in the amount of G-6-Pase enzyme. Thus, in SD and HFD rats, central nesfatin-1 may have decreased glucose production mainly via decreasing gluconeogenesis and PEPCK activity.[11]

Recently, it has been reported that ICV nesfatin-1 produced a dose-dependent delay of

gastric emptying.[11][12]

To further delineate the mechanism by which central nesfatin-1 modulates glucose homeostasis, we assessed the effects of central nesfatin-1 on the phosphorylation of several proteins in the

insulin sensitivity and improving glucose metabolism.[11]

AMPK is a key regulator of both lipid and glucose metabolism. It has been referred to as a metabolic master switch, because its activity is regulated by the energy status of the cell. In this study, we demonstrate that central nesfatin-1 resulted in increased phosphorylation of AMPK accompanied by a marked suppression of hepatic PEPCK activity, mRNA, and protein levels in both SD and HFD rats. Notably, central nesfatin-1 appears to prevent the obesity-driven decrease in phospho-AMPK levels in HFD-fed rats. Because hepatic AMPK controls glucose homeostasis mainly through the inhibition of gluconeogenic gene expression and glucose production, the suppressive effect of central nesfatin-1 on the HGP (Hepatic Glucose Production) can be attributed partly to its ability to suppress the expression of PEPCK mRNA and protein through AMPK activation. Furthermore, the activation of AMPK has been shown to enhance glucose uptake in skeletal muscle. Therefore, increased AMPK phosphorylation by central nesfatin-1 may also have been responsible for the improved glucose uptake in muscle.[11]

insulin sensitivity.[11]

The

negative-feedback mechanism in the regulation of metabolism and insulin sensitivity mediated by central nesfatin-1.[11]

See also

References

  1. S2CID 4366701
    .
  2. PMID 18625211
    .
  3. PMID 21224288
    .
  4. ^ ProSci inc. "Nesfatin-1 Recombinant Protein". Archived from the original on 11 April 2013. Retrieved 21 March 2013.
  5. S2CID 17973594
    .
  6. PMID 21862618
    .
  7. PMID 19883614
    .
  8. S2CID 3837217
    .
  9. PMID 19176321
    .
  10. PMID 22020667
    .
  11. ^
    PMID 22688332
    .
  12. PMID 19797401
    .

External links
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