Identification of Adropin as a Secreted Factor Linking Dietary Macronutrient Intake with Energy Homeostasis and Lipid Metabolism

Kumar, K. Ganesh; Trevaskis, James L.; Lam, Daniel D.; Sutton, Gregory M.; Koza, Robert A.; Chouljenko, Vladimir N.; Kousoulas, Konstantin G.; Rogers, Pamela M.; Kesterson, Robert A.; Thearle, Marie S.; Ferrante, Anthony W.; Mynatt, Randall L.; Burris, Thomas P.; Dong, Jesse Z.; Halem, Heather; Culler, Michael D.; Heisler, Lora K.; Stephens, Jacqueline M.; Butler, Andrew A.

doi:10.1016/j.cmet.2008.10.011

Cited by 407 publications

(744 citation statements)

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“…Compared with wild-type controls, the liver of Mc3rÀ/À mice exhibited increased expression of enzymes involved in lipogenesis and triglyceride synthesis and suppression of gluconeogenic enzymes. Microarray analysis of liver gene expression using the same protocol previously reported by our laboratory 81 produced a similar outcome (Figure 2a). The microarray data also suggested the upregulation of a cellular stress response in the liver of Mc3rÀ/À mice, with increased expression of genes involved in autophagy (Figures 2b and c), and in genes expressing heat-shock proteins and ubiquitination (our unpublished observations).…”

Section: A Role For Melanocortin-3 Receptors In the Defence Of Body Wsupporting

confidence: 58%

Unravelling the mysterious roles of melanocortin-3 receptors in metabolic homeostasis and obesity using mouse genetics

et al. 2014

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The central nervous melanocortin system maintains body mass and adiposity within a 'healthy' range by regulating satiety and metabolic homeostasis. Neural melanocortin-4 receptors (MC4R) modulate satiety signals and regulate autonomic outputs governing glucose and lipid metabolism in the periphery. The functions of melanocortin-3 receptors (MC3R) have been less well defined. We have observed that food anticipatory activity (FAA) is attenuated in Mc3rÀ/À mice housed in light:dark or constant dark conditions. Mc3rÀ/À mice subjected to the restricted feeding protocol that was used to induce FAA also developed insulin resistance, dyslipidaemia, impaired glucose tolerance and evidence of a cellular stress response in the liver. MC3Rs may thus function as modulators of oscillator systems that govern circadian rhythms, integrating signals from nutrient sensors to facilitate synchronizing peak foraging behaviour and metabolic efficiency with nutrient availability. To dissect the functions of MC3Rs expressed in hypothalamic and extra-hypothalamic structures, we inserted a 'lox-stop-lox' (TB) sequence into the Mc3r gene. Mc3r TB/TB mice recapitulate the phenotype reported for Mc3rÀ/À mice: increased adiposity, accelerated diet-induced obesity and attenuated FAA. The ventromedial hypothalamus exhibits high levels of Mc3r expression; however, restoring the expression of the LoxTB Mc3r allele in this nucleus did not restore FAA. However, a surprising outcome came from studies using Nestin-Cre to restore the expression of the LoxTB Mc3r allele in the nervous system. These data suggest that 'non-neural' MC3Rs have a role in the defence of body weight. Future studies examining the homeostatic functions of MC3Rs should therefore consider actions outside the central nervous system.International Journal of Obesity Supplements (2014) 4, S37--S44; doi:10.1038/ijosup.2014.10Keywords: melanocortin; metabolism; glucose; lipids; hypothalamus; feeding The central nervous melanocortin system forms a neural 'nutrientsensing' network, connecting signals of metabolic state with centres of the brain that regulate ingestive behaviours and metabolic homeostasis. 1 Genetic screens using morbidly obese individuals identified carriers with mutations in the melanocortin system, indicating that studying the melanocortin system has clinical relevance. 2 Nonsense mutations in the Proopiomelanocortin (POMC) gene 3 or the melanocortin-4 receptor (MC4R) gene are associated with hyperphagia and obesity. 4,5 MC3R mutations have also been suggested to be a predisposing factor for excessive weight gain, 6 although the association between MC3R mutations and obesity is less clear when compared with MC4R mutations.Data obtained from human genetics and animal models suggested that further study of the central nervous melanocortin system, and particularly MC4Rs, could lead to new therapies against obesity. 7 Although this outcome has yet to be realized, the information gathered from investigating this system significantly advanced the understanding of neural syst...

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Section: A Role For Melanocortin-3 Receptors In the Defence Of Body Wsupporting

confidence: 58%

Unravelling the mysterious roles of melanocortin-3 receptors in metabolic homeostasis and obesity using mouse genetics

et al. 2014

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“…Adropin is encoded by the Energy Homeostasis Associated (Enho) gene that is widely expressed in the central nervous system, as well as peripheral tissues such as liver, the heart and skeletal muscles [14][15][16]. While the mechanism of release remains controversial, the rapid regulation according to energy and nutritional status has been observed.…”

Section: Discussionmentioning

confidence: 99%

First and third trimester serum concentrations of adropin and copeptin in gestational diabetes mellitus and normal pregnancy

Dąbrowski

Jarmużek²,

Gondek³

et al. 2016

Ginekol Pol

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Objectives: Gestational diabetes mellitus (GDM) is a metabolic disease diagnosed in 1.7% up to 11.6% pregnancies. The prevalence of adverse pregnancy outcome is significantly higher in the case of early onset of diabetes mellitus. Adropin is a hormone promoting carbohydrate oxidation over fat oxidation, and influence nitric oxide synthase. Copeptin is a cleavage product of the vasopressin precursor recently correlated with diabetes mellitus. The aim of the study was to determine maternal serum adropin and copeptin concentrations in women with early and late manifestation of GDM and to discuss their potential role as biochemical markers of insulin resistance. Material and methods:Case-control study on 58 pregnant Caucasian women. Serum levels of adropin and copeptin were assessed in patients with early onset (GDM1) and classical gestational diabetes mellitus (GDM2). Complications such as macrosomia and hypotrophy were evaluated. Results:There was no significant difference between the study and the control group (age, BMI, parity). Fetal growth disturbance rate was 37.5% in GDM1, 11% in GDM2 and 6% in controls. Adropin concentration in GDM patients was significantly higher than in control group (p < 0.001), but there was no difference between GDM1 and GDM2 group. High serum concentration of adropin positively correlated with elevated HbA 1c (p < 0.05). The groups did not differ in terms of copeptin serum concentration. Conclusions:High adropin serum concentration in GDM patients is associated with increased risk of fetal growth disturbances, possibly due to improper placentation. According to our prospective study, neither copeptin nor adropin serum concentration are useful to discriminate between early and late onset of gestational diabetes mellitus.

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“…Loss of NO bioavailability is a cardinal feature of endothelial dysfunction that precedes the development of overt atherosclerosis and is an independent predictor of the development of SVG occlusion.The reduced circulating adropin concentrations are correlated with metabolic disorders that are associated with insulin resistance and obesity. These metabolic disorders are related to the progression of coronary atherosclerosis and increased incidence of cardiovascular events such as SVG occlusion [7] and acute coronary syndromes [14].…”

Section: Discussionmentioning

confidence: 99%

“…Adropin is a recently identified bioactive protein that is encoded by the energy homeostasis associated gene (Enho) and is expressed in the liver and brain [7]. Adropin appears to participate in the maintenance of energy homeostasis and insulin response, which is closely related to the development and progression of atherogenesis [7].…”

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confidence: 99%

Adropin: A New Marker for Predicting Late Saphenous Vein Graft Disease after Coronary Artery Bypass Grafting

Demircelik¹,

Çakmak²,

Nazlı³

et al. 2014

CIM

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Purpose: Saphenous vein graft disease (SVGD), defined as an occlusion of 50% or more of the SVG excluding distal anastomotic occlusion, is an important predictor of morbidity after coronary artery bypass grafting (CABG). Late graft occlusion is a serious complication that often limits the use of the saphenous vein as a coronary bypass graft. Late graft occlusion is particularly common in old, degenerated venous grafts with advanced atherosclerotic plaques. Adropin has been implicated in the homeostatic control of metabolism. The purpose of this study was to investigate whether serum adropin levels are associated with late SVGD following CABG.Methods: Thirty-eight patients with SVGD involving at least one graft (occluded group; 14 females, 24 males) and 42 patients with a patent saphenous vein graft (patent group; 15 females, 27 males) were enrolled in this study. Venous blood samples were taken from all of the participants to measure plasma adropin levels using an enzyme-linked immunsorbent assay kit. Results:The mean adropin level was significantly lower in the occluded group than in the patent group (3.2 ± 0.71 vs. 4.9 ± 1.51 ng/mL, p < 0.001). Multivariate regression analysis showed that the adropin level was the independent predictor of late saphenous vein graft occlusion.Conclusions: Adropin levels are lower in patients with late saphenous vein graft occlusion and these reduced adropin levels, together with other factors, may lead to saphenous vein graft occlusion. Larger and prospective studies are needed to determine if adropin plays a role in the pathogenesis of SVGD.

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Identification of Adropin as a Secreted Factor Linking Dietary Macronutrient Intake with Energy Homeostasis and Lipid Metabolism

Cited by 407 publications

References 42 publications

Unravelling the mysterious roles of melanocortin-3 receptors in metabolic homeostasis and obesity using mouse genetics

Unravelling the mysterious roles of melanocortin-3 receptors in metabolic homeostasis and obesity using mouse genetics

First and third trimester serum concentrations of adropin and copeptin in gestational diabetes mellitus and normal pregnancy

Adropin: A New Marker for Predicting Late Saphenous Vein Graft Disease after Coronary Artery Bypass Grafting

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