46 research outputs found
Ghrelin Modulates the fMRI BOLD Response of Homeostatic and Hedonic Brain Centers Regulating Energy Balance in the Rat
The orexigenic gut-brain peptide, ghrelin and its G-protein coupled receptor, the growth hormone secretagogue receptor
1a (GHS-R1A) are pivotal regulators of hypothalamic feeding centers and reward processing neuronal circuits of the brain.
These systems operate in a cooperative manner and receive a wide array of neuronal hormone/transmitter messages and
metabolic signals. Functional magnetic resonance imaging was employed in the current study to map BOLD responses to
ghrelin in different brain regions with special reference on homeostatic and hedonic regulatory centers of energy balance.
Experimental groups involved male, ovariectomized female and ovariectomized estradiol-replaced rats. Putative modulation
of ghrelin signaling by endocannabinoids was also studied. Ghrelin-evoked effects were calculated as mean of the BOLD
responses 30 minutes after administration. In the male rat, ghrelin evoked a slowly decreasing BOLD response in all studied
regions of interest (ROI) within the limbic system. This effect was antagonized by pretreatment with GHS-R1A antagonist
JMV2959. The comparison of ghrelin effects in the presence or absence of JMV2959 in individual ROIs revealed significant
changes in the prefrontal cortex, nucleus accumbens of the telencephalon, and also within hypothalamic centers like the
lateral hypothalamus, ventromedial nucleus, paraventricular nucleus and suprachiasmatic nucleus. In the female rat, the
ghrelin effects were almost identical to those observed in males. Ovariectomy and chronic estradiol replacement had no
effect on the BOLD response. Inhibition of the endocannabinoid signaling by rimonabant significantly attenuated the
response of the nucleus accumbens and septum. In summary, ghrelin can modulate hypothalamic and mesolimbic
structures controlling energy balance in both sexes. The endocannabinoid signaling system contributes to the
manifestation of ghrelin’s BOLD effect in a region specific manner. In females, the estradiol milieu does not influence the
BOLD response to ghrelin
Impact of Sustained Weight Loss Achieved through Roux-en-Y Gastric Bypass or a Lifestyle Intervention on Ghrelin, Obestatin, and Ghrelin/Obestatin Ratio in Morbidly Obese Patients
Ablations of Ghrelin and Ghrelin Receptor Exhibit Differential Metabolic Phenotypes and Thermogenic Capacity during Aging
mice are adaptive. mice.Our data therefore suggest that GHS-R ablation activates adaptive thermogenic function(s) in BAT and increases EE, thereby enabling the retention of a lean phenotype. This is the first direct evidence that the ghrelin signaling pathway regulates fat-burning BAT to affect energy balance during aging. This regulation is likely mediated through an as-yet-unidentified new ligand of GHS-R