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GHRL (Ghrelin and obestatin prepropeptide)

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Summary of GHRL

GHRL is the gene that codes for the peptide hormone, ghrelin. Ghrelin is considered a multi-functional hormone that is mainly produced by specialized stomach cells (R).  It is also produced by various tissues and organs including the gut, pancreas, kidney, reproductive organs, placenta, bone, and brain (R, R2, R3).

 Injections of Ghrelin in both humans and mice have been shown to increase food intake in a dose-dependent manner: the more Ghrelin, the more you eat (R, R2). Chronically elevated levels of ghrelin are associated with obesity, overeating, and inflammation-related diseases including Ulcerative Colitis, Crohns Disease, Pancreatitis, and possibly Rheumatoid Arthritis (R).

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The Function of GHRL

Obestatin may be the ligand for GPR39. May have an appetite-reducing effect resulting in decreased food intake. May reduce gastric emptying activity and jejunal motility.

Protein names

Recommended name:

Appetite-regulating hormone

Alternative name(s):

Growth hormone secretagogue
Growth hormone-releasing peptide
Motilin-related peptide
Protein M46
Ghrelin

GHRL SNPs

    To see your genotype, you should be logged in and have a file with your genotype uploaded.

  1. RS34911341 (GHRL) ??
  2. RS35683 (GHRL) ??
  3. RS42451 (GHRL) ??
  4. RS4684677 (GHRL) ??
  5. RS696217 (GHRL) ??

Top Gene-Substance Interactions

GHRL Interacts with These Diseases

Disease Score

Fixes

Ways to Increase Ghrelin

If you have low levels of ghrelin and are genetically predisposed to autoimmunity, you might want to increase ghrelin production.

  • Weight Loss - Ghrelin is lower in overweight people (R, R2).
  • Fasting - Ghrelin is secreted when the stomach is empty (R).
  • Fiber - Under fasting conditions, the more fiber consumed, the higher ghrelin levels (R).
  • Curcumin (R) -in diabetic animal models with gastroparesis.
  • Fish Oil (R)
  • Hi-maize Resistant Starch (R)
  • Zinc - In young pigs (R). 

Ways to Reduce Ghrelin

If you have high levels of ghrelin, are genetically predisposed to cancer or eating disorders, or are trying to lose weight, you might want to decrease ghrelin production. Here are some habitual ways to decrease ghrelin:

  • Protein (Red meat) - (R, R2) Ghrelin levels after eating a high protein meal was much lower compared to ghrelin levels after a high a calorie meal.
  • Adequate sleep - (R).
  • Fructose Restriction - (R) Ghrelin does not decrease as much after eating fructose. Lingering ghrelin may lead to overeating and contribute to weight gain and obesity.
  • Vitamin D3 (maybe) - Ghrelin was higher in people who were deficient in vitamin D3 (R).
  • Using Honey instead of sugar (maybe) (R).

Fixes Advanced

Additional Ways to Increase Ghrelin

  • Hydrogen water (R, R2).
  • Sleep deprivation - Even one night of sleep deprivation led to increased ghrelin levels in healthy volunteers (R).
  • Chronic stress increases ghrelin and appetite (R).
  • Adenosine has many of the effects of ghrelin by activating the growth hormone secretagogue receptor (R).

Additional Ways to Reduce Ghrelin

  • Ketogenic Diet (R)
  • Acupuncture (R)
  • Acute stress has been shown to decrease ghrelin levels and reduce appetite (R).

Substances That Increase GHRL

Substances Interaction Organism Category

Substances That Decrease GHRL

Substances Interaction Organism Category

Advanced Summary

     From NCBI Gene: Obesity

     From NCBI Gene: This gene encodes the ghrelin-obestatin preproprotein that is cleaved to yield two peptides, ghrelin and obestatin. Ghrelin is a powerful appetite stimulant and plays an important role in energy homeostasis. Its secretion is initiated when the stomach is empty, whereupon it binds to the growth hormone secretagogue receptor in the hypothalamus which results in the secretion of growth hormone (somatotropin). Ghrelin is thought to regulate multiple activities, including hunger, reward perception via the mesolimbic pathway, gastric acid secretion, gastrointestinal motility, and pancreatic glucose-stimulated insulin secretion. It was initially proposed that obestatin plays an opposing role to ghrelin by promoting satiety and thus decreasing food intake, but this action is still debated. Recent reports suggest multiple metabolic roles for obestatin, including regulating adipocyte function and glucose metabolism. Alternative splicing results in multiple transcript variants. In addition, antisense transcripts for this gene have been identified and may potentially regulate ghrelin-obestatin preproprotein expression. [provided by RefSeq, Nov 2014] From UniProt: Ghrelin is the ligand for growth hormone secretagogue receptor type 1 (GHSR). Induces the release of growth hormone from the pituitary. Has an appetite-stimulating effect, induces adiposity and stimulates gastric acid secretion. Involved in growth regulation. Obestatin may be the ligand for GPR39. May have an appetite-reducing effect resulting in decreased food intake. May reduce gastric emptying activity and jejunal motility.

Conditions with Increased Gene Activity

Condition Change (log2fold) Comparison Species Experimental variables Experiment name

Conditions with Decreased Gene Activity

Condition Change (log2fold) Comparison Species Experimental variables Experiment name

Technical

The following transcription factors affect gene expression:

  • NF-kappaB
  • PPAR-gamma1
  • PPAR-gamma2
  • AP-1
  • c-Jun
  • NF-kappaB1
  • C/EBPalpha
  • c-Fos
  • YY1

Tissue specificity:

Highest level in stomach. All forms are found in serum as well. Other tissues compensate for the loss of ghrelin synthesis in the stomach following gastrectomy.

Gene Pathways:

  • Signal Transduction
  • Metabolism of proteins
  • Neuroactive ligand-receptor interaction

Molecular Function:

  • Ghrelin Receptor Binding
  • G-Protein Coupled Receptor Binding
  • Growth Hormone-Releasing Hormone Activity
  • Protein Tyrosine Kinase Activator Activity

Biological Processes:

  • Actin Polymerization Or Depolymerization
  • Activation Of Mapk Activity
  • Adult Feeding Behavior
  • Cartilage Development
  • Cortisol Secretion
  • Decidualization
  • Dendrite Development
  • Excitatory Postsynaptic Potential
  • Gastric Acid Secretion
  • Glucose Metabolic Process
  • G-Protein Coupled Receptor Signaling Pathway
  • Growth Hormone Secretion
  • Hormone-Mediated Signaling Pathway
  • Negative Regulation Of Angiogenesis
  • Negative Regulation Of Apoptotic Process
  • Negative Regulation Of Circadian Sleep/Wake Cycle, Rem Sleep
  • Negative Regulation Of Endothelial Cell Proliferation
  • Negative Regulation Of Energy Homeostasis
  • Negative Regulation Of Inflammatory Response
  • Negative Regulation Of Insulin Secretion
  • Negative Regulation Of Interleukin-1 Beta Production
  • Negative Regulation Of Interleukin-6 Biosynthetic Process
  • Negative Regulation Of Locomotion
  • Negative Regulation Of Tumor Necrosis Factor Biosynthetic Process
  • Positive Regulation Of Appetite
  • Positive Regulation Of Circadian Sleep/Wake Cycle, Non-Rem Sleep
  • Positive Regulation Of Corticotropin Secretion
  • Positive Regulation Of Cortisol Secretion
  • Positive Regulation Of Cytosolic Calcium Ion Concentration
  • Positive Regulation Of Energy Homeostasis
  • Positive Regulation Of Growth Hormone Receptor Signaling Pathway
  • Positive Regulation Of Growth Hormone Secretion
  • Positive Regulation Of Insulin Secretion
  • Positive Regulation Of Multicellular Organism Growth
  • Positive Regulation Of Synapse Assembly
  • Regulation Of Cell Proliferation
  • Regulation Of Response To Food
  • Response To Estrogen
  • Response To Hormone
*synonyms

Synonyms/Aliases/Alternative Names of the Gene:

hypothetical protein| A306_08520| appetite-regulating hormone| appetite-regulating hormone isoform 1 preproprotein| appetite-regulating hormone-like protein| appetite-regulating hormone preproprotein| AS27_07339| AS28_07476| CB1_000105008| D623_10028325| exon 2- and 3-deleted preproghrelin| exon 2-deleted preproghrelin| Gh1-1| GHR| ghre| GH releasing peptide| ghrelin| ghrelin, growth hormone secretagogue receptor ligand| ghrelin/obestatin preprohormone| ghrelin/obestatin prepropeptide| ghrelin/obestatin preproprotein| GHRL-1| GRHL| growth hormone receptor| growth hormone-releasing peptide| growth hormone secretagogue| GW7_19468| H920_00304| I79_002355| In2c-preproghrelin| m46| M91_08237| M959_07740| MDA_GLEAN10023733| motilin related peptide| motilin-related peptide| MTLRP| MTLRPAP| MTLRP-AP| N301_10562| N308_16056| N309_14819| N310_06986| N312_11048| N321_08850| N325_09535| N326_10085| N327_11135| N330_13164| N335_00485| N336_08393| N340_10016| N341_06532| PAL_GLEAN10022285| PANDA_014496| prepro-appetite regulatory hormone| preproghrelin| prepro-ghrelin| preproghrelin-1| preproghrelin-2| proghrelin| TREES_T100014058| XELAEV_18023936mg| Y1Q_018963| Y956_14452| ghrl

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