Food Fails to Suppress Ghrelin Levels in Obese Humans

English, Patrick; Ghatei, Mohammed A.; Malik, Iqbal; Bloom, Stephen R.; Wilding, John

doi:10.1210/jcem.87.6.8738

Cited by 397 publications

(128 citation statements)

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“…We should also note that the obese subjects displayed blunted meal effects. It was reported previously in a group of subjects with an average BMI of 42.8 kg͞m 2 that a test meal failed to suppress ghrelin levels (44). Further studies would be required to test the hypothesis that meals of differing sizes or those taken at different times of day may have differential effects on appetite-regulating hormones.…”

Section: Discussionmentioning

confidence: 94%

Alterations in the dynamics of circulating ghrelin, adiponectin, and leptin in human obesity

Yildiz

Suchard

Wong

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

322

219

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Ghrelin plays a key role in the regulation of growth hormone secretion and energy homeostasis. Adiponectin is exclusively secreted by adipose tissue and is abundantly present in the circulation, with important effects on metabolism. We studied five lean and five obese young men [ages: 24.2 ؎ 1.0 (lean) and 21.8 ؎ 1.6 (obese) years (difference not significant); body mass indexes: 35.0 ؎ 1.3 and 23.0 ؎ 0.3 kg͞m 2 (P ‫؍‬ 0.01)], sampled blood every 7 min over 24 h, and measured ghrelin, adiponectin, and leptin in 2,070 samples for a total of 6,210 data points. Circulating 24-h ghrelin showed significant ultradian fluctuations and an orderly pattern of release in lean and obese subjects with similar pulsatility characteristics. Plasma adiponectin concentrations were significantly lower in the obese group, with lower pulse height. In contrast to leptin, which is secreted in an orderly manner, the 24-h patterns of adiponectin were not significantly different from random in both the lean and obese groups. We show here that adipocytes can simultaneously secrete certain hormones, such as leptin, in patterns that are orderly, whereas other hormones, such as adiponectin, are secreted in patterns that appear to be random. The cross-approximate entropy statistic revealed pattern synchrony among ghrelin-leptin, ghrelin-adiponectin, and leptinadiponectin hormone time series in the lean and obese subjects. Plasma ghrelin concentrations showed a nocturnal rise that exceeded the meal-associated increases in lean subjects, and this newly identified nocturnal rise was blunted in the obese. We suggest that the blunting of the nocturnal rise of ghrelin is a biological feature of human obesity.

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Section: Discussionmentioning

confidence: 94%

Alterations in the dynamics of circulating ghrelin, adiponectin, and leptin in human obesity

Yildiz

Suchard

Wong

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

322

219

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“…This is the only action of exogenously administered ghrelin that was reciprocally regulated in our ghrl Ϫ/Ϫ mice. Previous studies demonstrate that a high-fat diet decreases ghrelin levels in rodents (27) and that plasma ghrelin levels also are lower in obese humans (18,19). This reduction in ghrelin secretion in situations of positive energy balance may, together with increased leptin secretion, reflect an adaptive counterregulatory response, to push metabolic fuel preference toward lipid utilization under conditions of nutrient excess.…”

Section: Discussionmentioning

confidence: 95%

“…There is considerable evidence that exogenous ghrelin can markedly increase food intake and body weight when administered directly into the ventricles, and increases in plasma ghrelin levels observed before meals and during fasting have circumstantially linked ghrelin to the hunger response. However, peripheral administration of ghrelin exerts, at best, a very modest increase in food intake and body weight in rodents (3), and plasma ghrelin levels are reduced, rather than elevated, in genetically obese and hyperphagic rodents (17) and obese humans (18,19). Certain mutations in the ghrelin͞preproghrelin gene have been tenuously linked with early onset obesity, but the functional significance of these mutations remains unclear (20,21).…”

mentioning

confidence: 99%

Genetic deletion of ghrelin does not decrease food intake but influences metabolic fuel preference

Wortley

Anderson²,

García³

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

415

325

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Ghrelin is a recently identified growth hormone (GH) secretogogue whose administration not only induces GH release but also stimulates food intake, increases adiposity, and reduces fat utilization in mice. The effect on food intake appears to be independent of GH release and instead due to direct activation of orexigenic neurons in the arcuate nucleus of the hypothalamus. The effects of ghrelin administration on food intake have led to the suggestion that inhibitors of endogenous ghrelin could be useful in curbing appetite and combating obesity. To further study the role of endogenous ghrelin in appetite and body weight regulation, we generated ghrelin-deficient (ghrl ؊/؊ ) mice, in which the ghrelin gene was precisely replaced with a lacZ reporter gene. ghrl ؊/؊ mice were viable and exhibited normal growth rates as well as normal spontaneous food intake patterns, normal basal levels of hypothalamic orexigenic and anorexigenic neuropeptides, and no impairment of reflexive hyperphagia after fasting. These results indicate that endogenous ghrelin is not an essential regulator of food intake and has, at most, a redundant role in the regulation of appetite. However, analyses of ghrl ؊/؊ mice demonstrate that endogenous ghrelin plays a prominent role in determining the type of metabolic substrate (i.e., fat vs. carbohydrate) that is used for maintenance of energy balance, particularly under conditions of high fat intake.G hrelin is a 28-aa peptide produced predominantly in the stomach (1, 2) that has recently been identified as a ligand of the growth hormone (GH) secretogogue (GHS) receptor (GHS-R). Like other GHSs, activation of the receptor stimulates GH secretion from the pituitary gland (1). In addition to inducing GH release, administration of exogenous ghrelin also stimulates food intake and body weight gain (3-7), increases gastric motility and acid secretion (8, 9), and decreases lipid metabolism in mice and rats (3, 4). The effects of centrally administered ghrelin on food intake are independent of its ability to induce GH release and thought to result from its direct actions on the arcuate nucleus of the hypothalamus. Furthermore, recent studies have demonstrated that plasma ghrelin levels increase preceding meals and during fasting (10, 11). Thus, it has been suggested that ghrelin stimulates appetite and that inhibitors of endogenous ghrelin, therefore, could prove useful in reducing food intake and combating obesity (11).Supporting the possibility that ghrelin acts as a key regulator of appetite and food intake by actions on the hypothalamus, GHS-R is colocalized with neuropeptide Y (NPY)͞agouti-related protein (AgRP) neurons (12) in the arcuate nucleus, a region that is responsive to circulating peripheral nutrients and hormones and critically involved in the regulation of food intake (13). Indeed, ghrelin stimulates the spontaneous activity of these neurons (14), and central ghrelin administration increases NPY and AgRP gene expression (15). Moreover, ghrelin-immunoreactivity has been reported in the h...

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“…For example, the food intake in the OD group decreased at 125 min, whereas IVIM-DWI showed that the obvious inhibition of the hypothalamic D value was at 65 and 95 min. One reason may be that patients with obesity had an abnormal high level of ghrelin which was maintained over longer time after meals so that no significant decreased food intake was observed from 0 to 95 min [45,46] and the food intake between meals was increased. In rodents, the inhibition signal ahead of feeding behavior may trigger a dynamic process of continuously decreasing subjective hunger and enhanced the effect of the drug.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Feeding Behavior on Hypothalamus in Obese Type 2 Diabetic Rats with Glucagon-like Peptide-1 Receptor Agonist Intervention

Lu¹,

Chen²,

Yan³

et al. 2018

Obes Facts

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Objective: To investigate the utility of intravoxel incoherent motion-diffusion weighted imaging (IVIM-DWI) derived parameters in hypothalamus for monitoring the effect of Exendin-4 (Ex-4) intervention on the feeding behavior in obese diabetic rats within early feeding. Methods: 21 obese and 19 non-obese rats which were treated with streptozotocin injections were initially divided into an obese diabetes group (OD, n = 10), a non-obese diabetes group (D, n = 8), an obese group (O, n = 9) and a non-obese group (N, n = 9). Then, the rats in the 4 groups received subcutaneous injections of Ex-4, and feeding behavior was examined at 5, 35, 65, 95, and 125 min. The hypothalamic function was evaluated by IVIM-DWI. Finally, the relationship between the hypothalamic function and the amount of food intake was analyzed. Results: In comparison with the N group, the food intake significantly decreased in the O , OD, and D groups in response to Ex-4. Furthermore, a significant positive correlation was found between food intake and D values at different times from 5 to 125 min after Ex-4 intervention in all 4 groups. Conclusion: A direct correlation between the change of hypothalamic function and feeding behavior was detected in OD rats with Ex-4 intervention in the early feeding period. The hypothalamic D value derived from IVIM-DWI is promising to reflect the dynamic change of hypothalamic function due to intervention.

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Food Fails to Suppress Ghrelin Levels in Obese Humans

Cited by 397 publications

References 0 publications

Alterations in the dynamics of circulating ghrelin, adiponectin, and leptin in human obesity

Alterations in the dynamics of circulating ghrelin, adiponectin, and leptin in human obesity

Genetic deletion of ghrelin does not decrease food intake but influences metabolic fuel preference

The Effect of Feeding Behavior on Hypothalamus in Obese Type 2 Diabetic Rats with Glucagon-like Peptide-1 Receptor Agonist Intervention

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