Effect of Des-acyl Ghrelin on Adiposity and Glucose Metabolism

Zhang, Weizhen; Chai, Biaoxin; Li, Ji Yao; Wang, Hui; Mulholland, Michael W.

doi:10.1210/en.2008-0263

Cited by 129 publications

(115 citation statements)

References 31 publications

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“…A regulatory role of UAG on adipogenesis has been reported in animal studies (3,23). Zhang et al (23) reported a reduction in white adipose tissue and resistance to high-fat diet-induced obesity with an increase in plasma UAG concentrations in transgenic fatty acid-binding protein 4 mice.…”

Section: Discussionmentioning

confidence: 92%

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Unacylated ghrelin is associated with changes in body composition and body fat distribution during long-term exercise intervention

Cederberg

Rajala

Koivisto

et al. 2011

European Journal of Endocrinology

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Objective: Ghrelin, a gut-brain peptide involved in energy homeostasis, circulates predominantly (O90%) in unacylated form. Previous studies, however, have focused on total and acylated ghrelin, and the role of unacylated ghrelin (UAG) is not well understood. Particularly, the association of UAG with weight loss and changes in body composition in adults remains unclear. We hypothesized that exercise-associated increase in UAG level is associated with weight loss, favorable changes in body composition, and body fat distribution. Design and methods: A prospective study of 552 young men (mean age 19.3 and range 19-28 years) undergoing military service with structured 6-month exercise training program. Exercise performance, body composition, and biochemical measurements were obtained at baseline and follow-up. Association between changes in UAG levels and body composition and body fat distribution were evaluated. Results: An increase in UAG level during the exercise intervention was associated with reduced weight, fat mass (FM), fat percentage (fat %), and waist circumference, but not with fat-free mass. Inverse associations of changes in UAG level with changes in waist circumference and fat % were independent of weight at baseline, and changes in weight and exercise performance. Associations of changes in UAG level with waist circumference were significantly stronger than with fat % after the adjustment for confounding variables. Conclusion: UAG is associated with changes in body weight and body composition during an intensive long-term exercise intervention in young men. The association of UAG levels with changes in central obesity was stronger than with total FM.

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Section: Discussionmentioning

confidence: 92%

“…Zhang et al (23) reported a reduction in white adipose tissue and resistance to high-fat diet-induced obesity with an increase in plasma UAG concentrations in transgenic fatty acid-binding protein 4 mice. In contrast, Thompson et al (3) observed parallel adipogenic effects of UAG with AG, via a mechanism independent of the GHS-R 1a in rats.…”

Section: Discussionmentioning

confidence: 99%

Unacylated ghrelin is associated with changes in body composition and body fat distribution during long-term exercise intervention

Cederberg

Rajala

Koivisto

et al. 2011

European Journal of Endocrinology

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“…However, direct metabolic effects of DAG cannot be excluded in view of the reported GHS-R1a-independent (AG-independent) effects of DAG, which include improved glycemic control through the modulation of glucose and medium-chain fatty acid uptake (2,6,35,36). Another indication of the importance of DAG levels as a potential physiological inhibitor of AG action has been reported already by the above-mentioned studies of transgenic mice overexpressing DAG (32,33,37), which were lighter and shorter compared with controls. In another example of its antagonistic effects, DAG was found to suppress AG-induced neuronal activity in the arcuate nucleus of rats, thus suppressing the induction of food intake by AG (21).…”

Section: European Journal Of Endocrinologymentioning

confidence: 98%

“…Glucose tolerance tests showed glucose levels to be significantly lower in Fabp4-ghrelin transgenic mice than in the controls after glucose administration. Insulin sensitivity testing showed that Fabp4-ghrelin transgenic mice exhibited a significant greater hypoglycemic response to insulin (33). The inhibition of AG action by GHS-R1a blockade might, however, have unwanted side effects.…”

Section: European Journal Of Endocrinologymentioning

confidence: 99%

Does des-acyl ghrelin improve glycemic control in obese diabetic subjects by decreasing acylated ghrelin levels?

Özcan¹,

Neggers²,

Miller³

et al. 2014

European Journal of Endocrinology

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Objective: The objective of this study was to assess the effects of a continuous overnight infusion of des-acyl ghrelin (DAG) on acylated ghrelin (AG) levels and glucose and insulin responses to a standard breakfast meal (SBM) in eight overweight patients with type 2 diabetes. Furthermore, in the same patients and two additional subjects, the effects of DAG infusion on AG concentrations and insulin sensitivity during a hyperinsulinemic-euglycemic clamp (HEC) were assessed. Research design and methods: A double-blind, placebo-controlled cross-over study design was implemented, using overnight continuous infusions of 3 and 10 mg DAG/kg per h and placebo to study the effects on a SBM. During a HEC, we studied the insulin sensitivity. Results: We observed that, compared with placebo, overnight DAG administration significantly decreased postprandial glucose levels, both during continuous glucose monitoring and at peak serum glucose levels. The degree of improvement in glycemia was correlated with baseline plasma AG concentrations. Concurrently, DAG infusion significantly decreased fasting and postprandial AG levels. During the HEC, 2.5 h of DAG infusion markedly decreased AG levels, and the M-index, a measure of insulin sensitivity, was significantly improved in the six subjects in whom we were able to attain steady-state euglycemia. DAG administration was not accompanied by many side effects when compared with placebo. Conclusions: DAG administration improves glycemic control in obese subjects with type 2 diabetes through the suppression of AG levels. DAG is a good candidate for the development of compounds in the treatment of metabolic disorders or other conditions with a disturbed AG:DAG ratio, such as type 2 diabetes mellitus or Prader-Willi syndrome.

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“…In 3T3-L1 cell lines, over-expression of ghrelin significantly inhibits differentiation of adipocytes (Zhang et al, 2004) and markedly decreases mRNA and protein levels of PPAR , a marker of adipocyte differentiation. Over-expression of ghrelin in adipose tissue under the control of FABP4 promoter (Zhang et al, 2008) significant decreases the amount of adipose tissue and renders the mice resistant to diet induced obesity, which indicate that ghrelin may impair the development of adipose tissue (Zhang et al, 2008).…”

Section: Ghrelin and Cell Differentiationmentioning

confidence: 99%

Ghrelin, a Gastric Hormone with Diverse Functions

Li¹,

Luo²,

Li³

et al. 2012

Chemical Biology

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Effect of Des-acyl Ghrelin on Adiposity and Glucose Metabolism

Cited by 129 publications

References 31 publications

Unacylated ghrelin is associated with changes in body composition and body fat distribution during long-term exercise intervention

Unacylated ghrelin is associated with changes in body composition and body fat distribution during long-term exercise intervention

Does des-acyl ghrelin improve glycemic control in obese diabetic subjects by decreasing acylated ghrelin levels?

Ghrelin, a Gastric Hormone with Diverse Functions

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