It’s all about ‘Gherelin’ do you know ???

Nutrients and diet have greater impact on expression of genes, recent research is going on about interaction of nutrients with gene expression. So, the fields which are dealing such research are nutrigenetics and nutrigenomics.

Epigenetic modifications are caused by nutrients, so Ghrelin gene is important in this scenario. Ghrelin hormone is a 28 amino acid containing peptide, released in Gastro intestinal tract, was discovered in 1999. Ghrelin hormone is also known as hunger hormone, released by ghrelinergic cells and plays role as a neuropeptide.

As we know it’s an appetite promotor hormone so, when the stomach is empty it is released and when stomach is stretched, secretion stopped. To increase feed intake ghrelin, need AgRP (Agouti-related peptide). The insertion of ghrelin in vivo and vitro has involved this peptide in regulation of feed intake, regulation of body weight, GIT motility, CVS functions, enzyme release, cell proliferation and reproduction. Fasting has relationship with plasmatic ghrelin release in body.

The major kind is des-ghrelin, non-acylated ghrelin found in stomach. Ghrelin-O-acyltransferase (GOAT) is responsible for acyl-modifying ghrelin found in mice and human. This enzyme has major role in body of avian species. It is commonly found in globular region of proventriculus of chickens. It is involved in release of growth hormone but also inhibits feed intake.

• Avian Ghrelin (GOAT System)

Avian ghrelin was isolated in 2002. It contains 116 amino acids and share very little amino acid sequence homology with mammalian preproghrelin except in core UAG sequence. It is produced by splitting of 23 amino acids of preproghrelin. Ghrelin expression in proventriculus is maximum.

Ghrelin stimulate the GH release based on ghrelin discovery. Intravenous injection of ghrelin stimulates the release of GH in plasma. Avian Ghrelin gene is made up of two exons reported in 2003. The GHSR1a mRNA sequence in chicken codes 347 amino acids protein.

• Ghrelin Role in Avian Nutrition

Various studies shown that increase in plasma GH level in Leghorn chickens depend upon the quantity of injected Ghrelin. From these studies we can say that ghrelin is a GH releasing peptide in chickens.

Intracerebroventricular (ICV) administration of ghrelin strongly inhibit the feed intake dependent upon dosage. The release of corticotropin-releasing factor (CRF) containing neurons instead of activating NPY neurons in chicks stimulating by ghrelin.

Physiological Functions of Ghrelin:

Ghrelin perform different physiological functions in the body. Table summarize the different functions ghrelin in the different body parts.

• Growth Hormone Secretion:

Due to its binding with GHS-R1A on pituitary somatotropic cells, ghrelin cause stimulation of growth hormone secretion. Hypothalamus is also involved in the ghrelin induced GH secretion. GH secretion is also induced by desacyl ghrelin due to GH insulin regulation. Vagus nerve is also necessary induction of GH.

• Appetite and Food Intake:

Ghrelin level increases before feeding, during fasting and decreases after having a meal, it is secreted in pulsated manner. Administration of ghrelin by peripherally and centrally in rats increase food intake.  Hunger is controlled by orexigenic and anorexigenic peptides.

There are a lot of orexigenic peptides like neuropeptides Y (NPY), agouti related peptide (AGRP) and orexin but ghrelin is only orexigenic peptide which induce the appetite peripherally.

Ghrelin increase hunger through central as well as peripheral routes. It also takes place from Vagus nerve. Formation of ghrelin occur in the hypothalamus and ghrelin force arcuate nucleus (ARC) neurons producing NPY and AGRP.

It stimulates the arcuate nucleus (ARC), paraventricular nucleus (PVN) and dorsomedial region. Site of releasing of ghrelin is stomach, after secretion it reaches the brain. By triggering the activity of NPY or AGRP neurons, ghrelin increasing the hunger and food intake.

• Reproductive Function:

Ghrelin control the various function of male and female reproductive system. Ghrelin exerts various effect on hypothalamic pituitary gonadal axis and male and female reproduction systems as well as suppress the gonadotropin releasing hormone (GnRH), secretion of LH and FSH and induction of prolactin  nutrients. In the male reproductive system ghrelin and GHSR are present in the testis especially in Leydig and Sertoli cells.

Ghrelin modulates the testicular stem cells factor and damage the Leydig cells growth. Higher level of ghrelin can cause the male reproductive changing like in condition of energy deficiency.

In female reproductive system both ghrelin and GHSR are found in the ovary. Ghrelin either inhibit or stimulate the steroidogenesis (progesterone and estradiol production). It is studied that ghrelin boost the growth and stop the apoptosis of ovarian cells.

• Energy Homeostasis:

Body weight is influenced by the ghrelin level. Plasma ghrelin level has opposite effect on body weight in anorexia, cachexia and obesity. By increasing body weight due more feed intake, pregnancy and using high fat diet ghrelin going down.

While on the other hand, ghrelin level is high when body weight become low due to any reason like food restriction, chronic exercise and cachectic condition caused by anorexia nervosa.

• Gastric secretion and Gastrointestinal Motility:

Ghrelin administration route and dose effect the gastric secretion separately. When administrated peripherally gastric secretion higher. Moreover, ghrelin action with gastrin is to induce secretion of gastric acid.

And centrally administration either stimulate or stop the gastric secretion. On the other hand, gastrointestinal motility disorders are treated with ghrelin because of its therapeutic action.

• Anti-Inflammatory Function:

Ghrelin has anti-inflammatory actions and inhibit the production of cytokines-are pro-inflammatory. Due to anti-inflammatory action, ghrelin plays important role in many diseases control like pancreatitis, sepsis, arthritis and diabetic nephropathy.

• Bone Formation:

Ghrelin is also play important role in the growth of osteoblasts and differentiation and enhance the bone mineral density. Proliferation of osteoblasts stimulation by ghrelin through the PI3K and MAPK pathway. Oral administration of ghrelin cause bone formation and trigger the intramembranous bone repairing of calvarial bone defects in rats.

• Modulation of Ghrelin Level:

There are some impacts of dietary nutrients and different plant base compounds on ghrelin level. Level of ghrelin fluctuate throughout the day. It is highest in fasting, before having meal and at night while decreasing within 1 hour after feeding or having a meal.  Change in ghrelin level is depend upon the macronutrient of the diet.

Authors: Wasim Yousaf ^a, Hammad Ur Rehman Bajwa^b,*, Shehryar Shahid ^c, Muhammad Adeel Arshad ^d

1. Department of Animal Breeding and Genetics
2. Department of Parasitology
3. Department of Livestock Management
4. Department of Animal Nutrition