Surviving starvation: Essential role of the ghrelin-growth hormone axis

J. L. Goldstein, T. J. Zhao, R. L. Li, D. P. Sherbet, G. Liang, M. S. Brown

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

After brief starvation, vertebrates maintain blood glucose by releasing fatty acids from adipose tissue. The fatty acids provide energy for gluconeogenesis in liver and are taken up by muscle, sparing glucose. After prolonged starvation, fat stores are depleted, yet blood glucose can be maintained at levels sufficient to preserve life. Using a new mouse model, we demonstrate that survival after prolonged starvation requires ghrelin, an octanoylated peptide hormone that stimulates growth hormone (GH) secretion. We studied wild-type mice and mice lacking ghrelin as a result of knockout of GOAT, the enzyme that attaches octanoate to ghrelin. Micewere fed 40% of their normal intake for 7 d. Fat stores in both lines of mice became depleted after 4 d. On day 7, mice were fasted for 23h. In wild-type mice, ghrelin and GH rose massively, and blood sugar was maintained at ~60mg/dL. In Goat -/- mice, ghrelin was undetectable and GH failed to rise appropriately. Blood sugar declined to ~20mg/dL, and the animals were moribund. Infusion of ghrelin or GH prevented hypoglycemia. Our results support the following sequence: (1) Starvation lowers blood glucose; (2) glucose-sensing neurons respond by activating sympathetic neurons; (3) norepinephrine, released in the stomach, stimulates ghrelin secretion; (4) ghrelin releases GH, which maintains blood glucose. Thus, ghrelin lies at the center of a hormonal response that permits mice to survive an acute fast superimposed on chronic starvation.

Original languageEnglish (US)
Pages (from-to)121-127
Number of pages7
JournalCold Spring Harbor Symposia on Quantitative Biology
Volume76
DOIs
StatePublished - 2011

Fingerprint

Ghrelin
Starvation
Growth Hormone
Blood Glucose
Neurons
Fatty Acids
Fats
Glucose
Gluconeogenesis
Peptide Hormones
Hypoglycemia
Goats
Liver
Muscle
Vertebrates
Adipose Tissue
Stomach
Norepinephrine
Animals
Tissue

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Biochemistry

Cite this

Surviving starvation : Essential role of the ghrelin-growth hormone axis. / Goldstein, J. L.; Zhao, T. J.; Li, R. L.; Sherbet, D. P.; Liang, G.; Brown, M. S.

In: Cold Spring Harbor Symposia on Quantitative Biology, Vol. 76, 2011, p. 121-127.

Research output: Contribution to journalArticle

@article{6d19ae0b7e5b4b83b09b454180a14002,
title = "Surviving starvation: Essential role of the ghrelin-growth hormone axis",
abstract = "After brief starvation, vertebrates maintain blood glucose by releasing fatty acids from adipose tissue. The fatty acids provide energy for gluconeogenesis in liver and are taken up by muscle, sparing glucose. After prolonged starvation, fat stores are depleted, yet blood glucose can be maintained at levels sufficient to preserve life. Using a new mouse model, we demonstrate that survival after prolonged starvation requires ghrelin, an octanoylated peptide hormone that stimulates growth hormone (GH) secretion. We studied wild-type mice and mice lacking ghrelin as a result of knockout of GOAT, the enzyme that attaches octanoate to ghrelin. Micewere fed 40{\%} of their normal intake for 7 d. Fat stores in both lines of mice became depleted after 4 d. On day 7, mice were fasted for 23h. In wild-type mice, ghrelin and GH rose massively, and blood sugar was maintained at ~60mg/dL. In Goat -/- mice, ghrelin was undetectable and GH failed to rise appropriately. Blood sugar declined to ~20mg/dL, and the animals were moribund. Infusion of ghrelin or GH prevented hypoglycemia. Our results support the following sequence: (1) Starvation lowers blood glucose; (2) glucose-sensing neurons respond by activating sympathetic neurons; (3) norepinephrine, released in the stomach, stimulates ghrelin secretion; (4) ghrelin releases GH, which maintains blood glucose. Thus, ghrelin lies at the center of a hormonal response that permits mice to survive an acute fast superimposed on chronic starvation.",
author = "Goldstein, {J. L.} and Zhao, {T. J.} and Li, {R. L.} and Sherbet, {D. P.} and G. Liang and Brown, {M. S.}",
year = "2011",
doi = "10.1101/sqb.2011.76.010447",
language = "English (US)",
volume = "76",
pages = "121--127",
journal = "Cold Spring Harbor Symposia on Quantitative Biology",
issn = "0091-7451",
publisher = "Cold Spring Harbor Laboratory Press",

}

TY - JOUR

T1 - Surviving starvation

T2 - Essential role of the ghrelin-growth hormone axis

AU - Goldstein, J. L.

AU - Zhao, T. J.

AU - Li, R. L.

AU - Sherbet, D. P.

AU - Liang, G.

AU - Brown, M. S.

PY - 2011

Y1 - 2011

N2 - After brief starvation, vertebrates maintain blood glucose by releasing fatty acids from adipose tissue. The fatty acids provide energy for gluconeogenesis in liver and are taken up by muscle, sparing glucose. After prolonged starvation, fat stores are depleted, yet blood glucose can be maintained at levels sufficient to preserve life. Using a new mouse model, we demonstrate that survival after prolonged starvation requires ghrelin, an octanoylated peptide hormone that stimulates growth hormone (GH) secretion. We studied wild-type mice and mice lacking ghrelin as a result of knockout of GOAT, the enzyme that attaches octanoate to ghrelin. Micewere fed 40% of their normal intake for 7 d. Fat stores in both lines of mice became depleted after 4 d. On day 7, mice were fasted for 23h. In wild-type mice, ghrelin and GH rose massively, and blood sugar was maintained at ~60mg/dL. In Goat -/- mice, ghrelin was undetectable and GH failed to rise appropriately. Blood sugar declined to ~20mg/dL, and the animals were moribund. Infusion of ghrelin or GH prevented hypoglycemia. Our results support the following sequence: (1) Starvation lowers blood glucose; (2) glucose-sensing neurons respond by activating sympathetic neurons; (3) norepinephrine, released in the stomach, stimulates ghrelin secretion; (4) ghrelin releases GH, which maintains blood glucose. Thus, ghrelin lies at the center of a hormonal response that permits mice to survive an acute fast superimposed on chronic starvation.

AB - After brief starvation, vertebrates maintain blood glucose by releasing fatty acids from adipose tissue. The fatty acids provide energy for gluconeogenesis in liver and are taken up by muscle, sparing glucose. After prolonged starvation, fat stores are depleted, yet blood glucose can be maintained at levels sufficient to preserve life. Using a new mouse model, we demonstrate that survival after prolonged starvation requires ghrelin, an octanoylated peptide hormone that stimulates growth hormone (GH) secretion. We studied wild-type mice and mice lacking ghrelin as a result of knockout of GOAT, the enzyme that attaches octanoate to ghrelin. Micewere fed 40% of their normal intake for 7 d. Fat stores in both lines of mice became depleted after 4 d. On day 7, mice were fasted for 23h. In wild-type mice, ghrelin and GH rose massively, and blood sugar was maintained at ~60mg/dL. In Goat -/- mice, ghrelin was undetectable and GH failed to rise appropriately. Blood sugar declined to ~20mg/dL, and the animals were moribund. Infusion of ghrelin or GH prevented hypoglycemia. Our results support the following sequence: (1) Starvation lowers blood glucose; (2) glucose-sensing neurons respond by activating sympathetic neurons; (3) norepinephrine, released in the stomach, stimulates ghrelin secretion; (4) ghrelin releases GH, which maintains blood glucose. Thus, ghrelin lies at the center of a hormonal response that permits mice to survive an acute fast superimposed on chronic starvation.

UR - http://www.scopus.com/inward/record.url?scp=84867420714&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84867420714&partnerID=8YFLogxK

U2 - 10.1101/sqb.2011.76.010447

DO - 10.1101/sqb.2011.76.010447

M3 - Article

C2 - 21785007

AN - SCOPUS:84867420714

VL - 76

SP - 121

EP - 127

JO - Cold Spring Harbor Symposia on Quantitative Biology

JF - Cold Spring Harbor Symposia on Quantitative Biology

SN - 0091-7451

ER -