Role of the AMP-activated protein kinase (AMPK) signaling pathway in the orexigenic effects of endogenous ghrelin

Verhulst, Pieter-Jan; Janssen, Sara; Tack, Jan; Depoortere, Inge

doi:10.1016/j.regpep.2011.09.001

Cited by 25 publications

(28 citation statements)

References 33 publications

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“…In pools of NPY neurons, fasting increased the neuropeptides and Ghsr but decreased Ucp2 expression. In our study and others (Verhulst et al, 2012), fasting increased plasma ghrelin, a potent orexigenic peptide hormone. Presumably, the elevation of plasma ghrelin and Ghsr expression in NPY neurons intensifies neuronal sensitivity to ghrelin to drive the post-fasting hyperphagia (Bagnasco et al, 2003; Becskei et al, 2009; Kinzig et al, 2009; Teubner et al, 2013) and augment Npy / Agrp expression, which is found in fasted male mice (Verhulst et al, 2012).…”

Section: Discussionsupporting

confidence: 84%

“…Fasting alters ARC gene expression and, in particular, increases expression of orexigenic neuropeptides (Npy and Agrp ) and genes involved in ghrelin signaling ( Ghsr , Ucp2 ) (Briggs et al, 2013, 2010; Coppola et al, 2007; Palou et al, 2009; Verhulst et al, 2012). In our study, fasting increased Npy , Agrp , Ghsr , and Ucp2 expression in the ARC.…”

Section: Discussionmentioning

confidence: 99%

“…Fasting and diet-induced obesity (DIO) regulate expression of Npy , Agrp , Ghsr , and Ucp2 in the ARC (Briggs et al, 2014, 2013, 2010; Coppola et al, 2007; Verhulst et al, 2012), which may be a contributing mechanism underlying the ghrelin resistance seen in DIO (Briggs et al, 2014, 2010; Perreault et al, 2004). Furthermore, a high fat diet (HFD) or DIO inhibits ghrelin’s augmentation of hyperphagia (Gardiner et al, 2010; Perez-Tilve et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

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Differential gene regulation of GHSR signaling pathway in the arcuate nucleus and NPY neurons by fasting, diet-induced obesity, and 17β-estradiol

Yasrebi

Hsieh

Mamounis

et al. 2016

Molecular and Cellular Endocrinology

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Ghrelin’s receptor, growth hormone secretagogue receptor (GHSR), is highly expressed in the arcuate nucleus (ARC) and in neuropeptide Y (NPY) neurons. Fasting, diet-induced obesity (DIO), and 17β-estradiol (E2) influence ARC Ghsr expression. It is unknown if these effects occur in NPY neurons. Therefore, we examined the expression of Npy, Agrp, and GHSR signaling pathway genes after fasting, DIO, and E2 replacement in ARC and pools of NPY neurons. In males, fasting increased ARC Ghsr and NPY Foxo1 but decreased NPY Ucp2. In males, DIO decreased ARC and NPY Ghsr and Cpt1c. In fed females, E2 increased Agrp, Ghsr, Cpt1c, and Foxo1 in ARC. In NPY pools, E2 decreased Foxo1 in fed females but increased Foxo1 in fasted females. DIO in females suppressed Agrp and augmented Cpt1c in NPY neurons. In summary, genes involved in GHSR signaling are differentially regulated between the ARC and NPY neurons in a sex-dependent manner.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Differential gene regulation of GHSR signaling pathway in the arcuate nucleus and NPY neurons by fasting, diet-induced obesity, and 17β-estradiol

Yasrebi

Hsieh

Mamounis

et al. 2016

Molecular and Cellular Endocrinology

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“…injected with rapamycin (R0395-1MG, Sigma) or the vehicle (DMSO in artificial cerebrospinal fluid) 2 h before the start of the dark cycle (Cota et al 2006, Verhulst et al 2012; rapamycin was dissolved in DMSO at a concentration of 25 mg/ml and was used at a final concentration of 20 mg/2 ml. Following the infusion, the guide cannula remained inserted for w30 s to allow the drug to diffuse away from the cannula tip.…”

Section: Icv Injectionmentioning

confidence: 99%

A central role for the mammalian target of rapamycin in LPS-induced anorexia in mice

Yue

Wang

et al. 2014

Journal of Endocrinology

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Bacterial lipopolysaccharide (LPS), also known as endotoxin, induces profound anorexia. However, the LPS-provoked pro-inflammatory signaling cascades and the neural mechanisms underlying the development of anorexia are not clear. Mammalian target of rapamycin (mTOR) is a key regulator of metabolism, cell growth, and protein synthesis. This study aimed to determine whether the mTOR pathway is involved in LPS-induced anorexia. Effects of LPS on hypothalamic gene/protein expression in mice were measured by RT-PCR or western blotting analysis. To determine whether inhibition of mTOR signaling could attenuate LPS-induced anorexia, we administered an i.c.v. injection of rapamycin, an mTOR inhibitor, on LPS-treated male mice. In this study, we showed that LPS stimulates the mTOR signaling pathway through the enhanced phosphorylation of mTOR Ser2448 and p70S6K Thr389 . We also showed that LPS administration increased the phosphorylation of FOXO1 Ser256 , the p65 subunit of nuclear factor kappa B (P!0.05), and FOXO1/3a Thr24/32 (P!0.01). Blocking the mTOR pathway significantly attenuated the LPS-induced anorexia by decreasing the phosphorylation of p70S6K Thr389 , FOXO1 Ser256 , and FOXO1/3a Thr24/32 . These results suggest promising approaches for the prevention and treatment of LPS-induced anorexia.

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“…A role for the energy sensor AMP-activated protein kinase (AMPK) and its downstream effector uncoupling protein 2 (UCP2) in the stimulatory effect of ghrelin on NPY/AgRP expression and food intake has been previously suggested [46]. However, more recent data failed to support such findings, suggesting that AMPK and UCP2 do not play a major role in the orexigenic effect of endogenous ghrelin [47]. …”

Section: Ghrelinmentioning

confidence: 99%

Stomach - Key Player in the Regulation of Metabolism

Štimac¹,

Majanović

Franjić³

2014

Dig Dis

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Although the stomach is often perceived as a crude, food-grinding, muscular bag, scientific breakthroughs have shown us that in the case of the stomach there is more than meets the eye. The endocrine function of the stomach is mainly exerted through the actions of ghrelin, an acylated peptide hormone that is the first known and so far most extensively studied endogenous orexigenic substance. The satiety-hunger balance is kept in check by many anorexigenic gut hormones among which is the deacylated form of ghrelin - desacyl ghrelin. The interplay of gut hormones affects the brain directly, as most gut hormones cross the blood-brain barrier and bind to their respective receptors in the central nervous system. Other hormones like obestatin and nesfatin are secreted from the stomach along with ghrelin, yet their physiological function is to be elucidated. The importance of the satiety-hunger balance can be seen in its most typical derangement - obesity. Some studies imply that ghrelin, along with other gut hormones, plays an important part in the pathophysiology of obesity. More importantly, it seems that the mechanisms by which bariatric surgery procedures induce weight loss are primarily based on changing the gut hormone levels, including ghrelin. If proven, ghrelin antagonists could be the renaissance of pharmacological obesity treatment.

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Role of the AMP-activated protein kinase (AMPK) signaling pathway in the orexigenic effects of endogenous ghrelin

Cited by 25 publications

References 33 publications

Differential gene regulation of GHSR signaling pathway in the arcuate nucleus and NPY neurons by fasting, diet-induced obesity, and 17β-estradiol

Differential gene regulation of GHSR signaling pathway in the arcuate nucleus and NPY neurons by fasting, diet-induced obesity, and 17β-estradiol

A central role for the mammalian target of rapamycin in LPS-induced anorexia in mice

Stomach - Key Player in the Regulation of Metabolism

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