TY - JOUR
T1 - Obesity Impairs the Action of the Neuroendocrine Ghrelin System
AU - Zigman, Jeffrey M.
AU - Bouret, Sebastien G.
AU - Andrews, Zane B.
N1 - Funding Information:
This work was supported by a Monash Fellowship, Monash University, Australia, a National Health and Medical Research Council (NHMRC) Career Development Fellowship and NHMRC grants (NHMRC 1011274) to Z.B.A., the Foundation for Prader–Willi Research, the National Institutes of Health (NIH grants DK84142 and DK102780), and the EU FP7 integrated project (grant agreement no. 266408, ‘Full4Health’) to S.G.B., and the NIH (R01DK103884) and an International Research Alliance Grant with the Novo Nordisk Foundation Center for Basic Metabolic Research to J.M.Z.
Publisher Copyright:
© 2015 Elsevier Ltd.
PY - 2016/1/1
Y1 - 2016/1/1
N2 - Ghrelin is a metabolic hormone that promotes energy conservation by regulating appetite and energy expenditure. Although some studies suggest that antagonizing ghrelin function attenuates body weight gain and glucose intolerance on a high calorie diet, there is little information about the metabolic actions of ghrelin in the obese state. In this review, we discuss the novel concept of obesity-induced central ghrelin resistance in neural circuits regulating behavior, and impaired ghrelin secretion from the stomach. Interestingly, weight loss restores ghrelin secretion and function, and we hypothesize that ghrelin resistance is a mechanism designed to protect a higher body weight set-point established during times of food availability, to maximize energy reserves during a time of food scarcity. Ghrelin secretion from stomach cells is attenuated during diet-induced obesity (DIO).During DIO, ghrelin cells in the stomach no longer respond to secretory stimuli, such as norepinephrine and glucose.When energy is low, ghrelin drives biological adaptations that ensure the ability to seek, locate, and forage food, and enhances the rewarding properties of food.DIO prevents ghrelin action in the brain, causing a state of central ghrelin resistance; ghrelin can no longer increase food intake due to alterations in homeostatic feeding circuits and reward processing pathways.Ghrelin resistance is reversed with diet-induced weight loss, and this is a mechanism to defend a higher body weight set-point established during times of food availability, to maximize energy reserves when food becomes scarce.
AB - Ghrelin is a metabolic hormone that promotes energy conservation by regulating appetite and energy expenditure. Although some studies suggest that antagonizing ghrelin function attenuates body weight gain and glucose intolerance on a high calorie diet, there is little information about the metabolic actions of ghrelin in the obese state. In this review, we discuss the novel concept of obesity-induced central ghrelin resistance in neural circuits regulating behavior, and impaired ghrelin secretion from the stomach. Interestingly, weight loss restores ghrelin secretion and function, and we hypothesize that ghrelin resistance is a mechanism designed to protect a higher body weight set-point established during times of food availability, to maximize energy reserves during a time of food scarcity. Ghrelin secretion from stomach cells is attenuated during diet-induced obesity (DIO).During DIO, ghrelin cells in the stomach no longer respond to secretory stimuli, such as norepinephrine and glucose.When energy is low, ghrelin drives biological adaptations that ensure the ability to seek, locate, and forage food, and enhances the rewarding properties of food.DIO prevents ghrelin action in the brain, causing a state of central ghrelin resistance; ghrelin can no longer increase food intake due to alterations in homeostatic feeding circuits and reward processing pathways.Ghrelin resistance is reversed with diet-induced weight loss, and this is a mechanism to defend a higher body weight set-point established during times of food availability, to maximize energy reserves when food becomes scarce.
UR - http://www.scopus.com/inward/record.url?scp=84951859618&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84951859618&partnerID=8YFLogxK
U2 - 10.1016/j.tem.2015.09.010
DO - 10.1016/j.tem.2015.09.010
M3 - Review article
C2 - 26542050
AN - SCOPUS:84951859618
SN - 1043-2760
VL - 27
SP - 54
EP - 63
JO - Trends in Endocrinology and Metabolism
JF - Trends in Endocrinology and Metabolism
IS - 1
ER -