Article
Biochemistry & Molecular Biology
Kristie Conde, Danielle Kulyk, Allison Vanschaik, Sierra Daisey, Catherine Rojas, Kimberly Wiersielis, Ali Yasrebi, Thomas J. Degroat, Yuxiang Sun, Troy A. Roepke
Summary: The study found that the gut peptide ghrelin regulates energy homeostasis and reproduction by acting through its receptor, GHSR, in hypothalamic neurons. Estradiol increases the expression of GHSR in specific neurons and enhances the sensitivity to ghrelin. Knockout models lacking GHSR showed abolished gene expression changes and altered metabolism and fasting glucose levels in response to estradiol treatment. The knockouts were also resistant to weight gain and exhibited reduced anxiety-like behavior. These findings demonstrate a novel mechanism for estradiol and ghrelin to control the function of specific neurons.
Article
Biochemistry & Molecular Biology
Christina M. Merkley, Sydney L. Shuping, Jeffrey R. Sommer, Casey C. Nestor
Summary: The study found a direct connection between orexigenic AgRP neurons and reproductively critical kisspeptin neurons in sheep, providing neuroanatomical evidence for the central link between energy balance and reproduction.
Article
Biochemistry & Molecular Biology
Iris Stoltenborg, Fiona Peris-Sampedro, Erik Schele, Marie V. Le May, Roger A. H. Adan, Suzanne L. Dickson
Summary: The availability of Cre-based mouse lines has helped identify the neural circuitry driving hormone effects. As an alternative method, TRAP2 mice provide genetic access to hormone-activated populations. By utilizing TRAP2 mice, researchers visualized and stimulated ghrelin-activated cells, discovering their significant role in inducing an orexigenic response and impacting food choice.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Anuhya S. Kotta, Abigail S. Kelling, Karen A. Corleto, Yuxiang Sun, Erin D. Giles
Summary: Ghrelin, a hormone produced and secreted from the stomach, is known as an appetite stimulant, but recent research suggests it may also play a role in cancer progression. This article summarizes the relationships between ghrelin and various cancers and provides important considerations for future research.
Article
Behavioral Sciences
Maria P. Cornejo, Emilio R. Mustafa, Franco Barrile, Daniela Cassano, Pablo N. De Francesco, Jesica Raingo, Mario Perello
Summary: The GHSR, a highly expressed GPCR in the brain, regulates the activity of the mesocorticolimbic pathway and modulates reward-related behaviors by interacting with the hormone ghrelin.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2021)
Article
Biochemistry & Molecular Biology
Gimena Fernandez, Agustina Cabral, Pablo N. De Francesco, Maia Uriarte, Mirta Reynaldo, Daniel Castrogiovanni, Guillermina Zubiria, Andres Giovambattista, Sonia Cantel, Severine Denoyelle, Jean-Alain Fehrentz, Virginie Tolle, Helgi B. Schioth, Mario Perello
Summary: Food deprivation-induced activation of PVHCRF neurons involves GHSR signaling and a decrease in plasma LEAP2 levels, independent of ghrelin.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Endocrinology & Metabolism
Franco Barrile, Daniela Cassano, Gimena Fernandez, Pablo N. De Francesco, Mirta Reynaldo, Sonia Cantel, Jean-Alain Fehrentz, Jose Donato Jr, Helgi B. Schioth, Jeffrey M. Zigman, Mario Perello
Summary: This study found that ghrelin receptor (GHSR) is widely distributed in the mouse lateral hypothalamic area (LHA), mediating the effects of ghrelin on food intake. Local injections of ghrelin in LHA increase food intake and locomotor activity through the indirect recruitment of orexin neurons in LHA and activation of neurons in the arcuate nucleus (ARH). These findings provide a neuroanatomical and functional characterization of LHA GHSR neurons and their important role in regulating food intake.
PSYCHONEUROENDOCRINOLOGY
(2023)
Article
Endocrinology & Metabolism
Deepali Gupta, Anna M. Patterson, Sherri Osborne-Lawrence, Angie L. Bookout, Salil Varshney, Kripa Shankar, Omprakash Singh, Nathan P. Metzger, Corine P. Richard, Steven C. Wyler, Joel K. Elmquist, Jeffrey M. Zigman
Summary: The study investigated the role of acyl-ghrelin on GH secretion and metabolic actions by selectively deleting GHSR from somatotrophs. Results suggest that the direct engagement of GHSR-expressing somatotrophs is essential for acyl-ghrelin to stimulate GH secretion and influence its metabolic actions.
MOLECULAR METABOLISM
(2021)
Article
Biochemistry & Molecular Biology
Hao-Zheng Li, Xiao-Xia Shao, Ya-Fen Wang, Ya-Li Liu, Zeng-Guang Xu, Zhan-Yun Guo
Summary: By studying fish GHSRs, we found that LEAP2 is a more conserved ligand than ghrelin, which provides new insights into the functions of LEAP2 and ghrelin in different fish species.
Article
Biochemistry & Molecular Biology
Maria Paula Cornejo, Raphael G. P. Denis, Guadalupe Garcia Romero, Gimena Fernandez, Mirta Reynaldo, Serge Luquet, Mario Perello
Summary: Research has shown that ghrelin has a biphasic effect on energy balance by indirectly impacting energy expenditure and nutrient partitioning through its influence on food intake. The biphasic effect of ghrelin on food intake requires the integrity of Agouti-related peptide/neuropeptide Y-producing neurons in the hypothalamic arcuate nucleus, with various signals transiently counteracting ghrelin's orexigenic effect.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Hao-Zheng Li, Ya-Fen Wang, Yong-Shan Zheng, Ya-Li Liu, Zeng-Guang Xu, Zhan-Yun Guo
Summary: The present study found that the GHSRs of fish have different binding properties to ghrelin. The GHSRs of zebrafish and large yellow croaker have lost their binding ability to ghrelin, while the GHSR of the lobe-finned fish Latimeria chalumnae can efficiently bind to ghrelin. Instead of ghrelin, motilin is an efficient agonist for GHSR in Latimeria chalumnae. This suggests that GHSR might have two efficient agonists, ghrelin and motilin, in ancient fishes, but this feature might only be preserved in some extant fishes with ancient evolutionary origins.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Junewoo Na, Byong Seo Park, Doohyeong Jang, Donggue Kim, Thai Hien Tu, Youngjae Ryu, Chang Man Ha, Marco Koch, Sungchil Yang, Jae Geun Kim, Sunggu Yang
Summary: This study extensively characterizes the AgRP, POMC, and dopaminergic neurons in the hypothalamic arcuate nucleus (Arc). The distinct anatomical and physiological properties of these neurons in response to appetite-regulating hormones are identified. This research highlights the importance of hypothalamic Arc neurons in appetite control.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Endocrinology & Metabolism
Chunyan Zhao, Bin Wang, Yifan Liu, Chengcheng Feng, Shihong Xu, Wenqi Wang, Qinghua Liu, Jun Li
Summary: This study confirms the presence of two Kiss/Kissr systems in turbot, and suggests their positive involvement in controlling the reproduction of turbot. These findings provide preliminary information on how the Kiss/Kissr system regulates seasonal reproduction in turbot broodstock.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Genetics & Heredity
Xiangcang Ye, Zeyu Liu, Hye Won Han, Ji Yeon Noh, Zheng Shen, Da Mi Kim, Hongying Wang, Huiping Guo, Johnathan Ballard, Andrei Golovko, Benjamin Morpurgo, Yuxiang Sun
Summary: This study found that BPA promotes intestinal inflammation, leading to increased expression of GHSR and pro-inflammatory genes, as well as an increase in inflammatory cells in the colon. Both short- and long-term BPA exposure also elevated pro-inflammatory cells in the blood and peritoneal macrophages. The deletion of GHSR in macrophages resulted in a reduced pro-inflammatory response to BPA, suggesting that GHSR plays a key role in BPA-induced inflammation. Further research on the GHSR signaling mechanism in BPA intestinal immunotoxicity can help develop strategies to mitigate BPA toxicity and provide policy guidance for biosafety.
Article
Endocrinology & Metabolism
Deepali Gupta, Georgina K. C. Dowsett, Bharath K. Mani, Kripa Shankar, Sherri Osborne-Lawrence, Nathan P. Metzger, Brian Y. H. Lam, Giles S. H. Yeo, Jeffrey M. Zigman
Summary: Islets are important sites for the action of the hormone ghrelin, with expression of the ghrelin receptor (GHSR) found in alpha, beta, and somatostatin-secreting delta cells. Further analysis revealed that PP-expressing gamma cells in mice and humans are also likely direct targets for ghrelin and its antagonist LEAP2.
Article
Biochemistry & Molecular Biology
Sara L. Deschaine, Mehdi Farokhnia, Adriana Gregory-Flores, Lia J. Zallar, Zhi-Bing You, Hui Sun, Deon M. Harvey, Renata C. N. Marchette, Brendan J. Tunstall, Bharath K. Mani, Jacob E. Moose, Mary R. Lee, Eliot Gardner, Fatemeh Akhlaghi, Marisa Roberto, James L. Hougland, Jeffrey M. Zigman, George F. Koob, Leandro F. Vendruscolo, Lorenzo Leggio
Summary: Alcohol decreases ghrelin levels in both rats and humans, but this decrease is not in proportion to alcohol's caloric value or through direct interaction with the ghrelin system.
Article
Medicine, Research & Experimental
Kripa Shankar, Shota Takemi, Deepali Gupta, Salil Varshney, Bharath K. Mani, Sherri Osborne-Lawrence, Nathan P. Metzger, Corine P. Richard, Eric D. Berglund, Jeffrey M. Zigman
Summary: Insulin suppresses ghrelin secretion by acting on insulin receptors (IRs) expressed on ghrelin cells, rather than ingested or metabolized macronutrients.
Article
Biology
Alex Reichenbach, Rachel E. Clarke, Romana Stark, Sarah Haas Lockie, Mathieu Mequinion, Harry Dempsey, Sasha Rawlinson, Felicia Reed, Tara Sepehrizadeh, Michael DeVeer, Astrid C. Munder, Juan Nunez-Iglesias, David C. Spanswick, Randall Mynatt, Alexxai Kravitz, Christopher Dayas, Robyn Brown, Zane B. Andrews
Summary: This study found that metabolic sensing in AgRP neurons is crucial for regulating motivation for food reward by modulating dopamine release in the striatum.
Article
Endocrinology & Metabolism
Julieta P. Aguggia, Maria P. Cornejo, Gimena Fernandez, Pablo N. De Francesco, Bharath K. Mani, Daniela Cassano, Agustina Cabral, Spring Valdivia, Guadalupe Garcia Romero, Mirta Reynaldo, Jean-Alain Fehrentz, Jeffrey M. Zigman, Mario Perello
Summary: Recent evidence suggests that Ghrelin may exert some of its actions via the supramammillary nucleus (SuM). In this study, researchers investigated the effects of Ghrelin in the SuM using a GHSR-eGFP mouse model. They found that centrally injected Ghrelin reached the SuM and induced c-Fos expression. Calorie restriction and binge-like eating also had an impact on the SuM cells. However, intra-SuM injected Ghrelin did not have an immediate effect on food intake, locomotor activity, behavioral arousal, or spatial memory but improved recognition memory.
PSYCHONEUROENDOCRINOLOGY
(2022)
Article
Endocrinology & Metabolism
Sasha Rawlinson, Alex Reichenbach, Rachel E. Clarke, Juan Nunez-Iglesias, Harry Dempsey, Sarah H. Lockie, Zane B. Andrews
Summary: This study found that hypoglycemia and glucose deprivation inhibit the activity of VMH Vglut2 neurons, while hyperglycemia does not. This suggests that VMH Vglut2 neurons may not be the main driving factors required for initiating the counterregulatory response.
Article
Neurosciences
Rachel E. Clarke, Katharina Voigt, Alex Reichenbach, Romana Stark, Urvi Bharania, Harry Dempsey, Sarah H. Lockie, Mathieu Mequinion, Moyra Lemus, Bowen Wei, Felicia Reed, Sasha Rawlinson, Juan Nunez-Iglesias, Claire J. Foldi, Alexxai V. Kravitz, Antonio Verdejo-Garcia, Zane B. Andrews
Summary: By modeling neural network dynamics, researchers identified a novel pathway from the medial prefrontal cortex (mPFC) to the lateral hypothalamus (LH) involved in stress-related control of food intake. Inhibition of this pathway increased feeding and sucrose seeking during mild stressors, while activation suppressed food intake and sucrose seeking in mice.
BIOLOGICAL PSYCHIATRY
(2023)
Article
Behavioral Sciences
Helen J. Rushby, Zane B. Andrews, Matthew D. W. Piper, Christen K. Mirth
Summary: Modifying the proportions of macronutrients in the diet has significant effects on the reproduction and health of animals. In this study, using capillary feeding assays, we explored how adult fruit flies compromise their nutrient intake when limited to single diets. We found that young male and female flies compromised by consuming more food on diets with low protein to carbohydrate ratios. Additionally, female flies showed greater variations in carbohydrate intake compared to males, and mated females consumed more food than virgin females.
Article
Endocrinology & Metabolism
Romana Stark, Jack Feehan, Aya Mousa, Zane B. B. Andrews, Barbora de Courten
Summary: This study identified an association between liver-expressed antimicrobial peptide 2 (LEAP2) levels and key cardiometabolic risk factors in individuals with overweight and obesity, including body fat, insulin secretion, and insulin resistance. LEAP2 may represent a potential therapeutic target to promote insulin secretion in individuals with type 2 diabetes and obesity.
DIABETES OBESITY & METABOLISM
(2023)
Review
Endocrinology & Metabolism
Mario Perello, Suzanne L. Dickson, Jeffrey M. Zigman, Lorenzo Leggio
Summary: The stomach-derived peptide ghrelin, discovered in 1999, is an endogenous agonist of the growth hormone secretagogue receptor (GHSR) and plays key roles in various physiological functions. Its non-acylated form, desacyl-ghrelin, has a less well-understood physiological role. To establish a consistent nomenclature, experts in the field have proposed using the terms ghrelin and desacyl-ghrelin for the hormones, GHSR for the receptor, and LEAP2 for a recently recognized GHSR antagonist/inverse agonist.
JOURNAL OF NEUROENDOCRINOLOGY
(2023)
Article
Medicine, Research & Experimental
Jing Tian, Lan Guo, Tienju Wang, Kun Jia, Russell H. Swerdlow, Jeffrey M. Zigman, Heng Du
Summary: Studies have found that cognitive decline is often reported in elderly individuals, and hippocampal function declines with age. The plasma levels of LEAP2 and ghrelin were found to change in cognitively normal individuals older than 60. Experiments with aged mice showed that restoring the balance of LEAP2 and ghrelin improved cognitive performance and mitigated age-related hippocampal deficiencies. Therefore, the LEAP2/ghrelin molar ratio may serve as a biomarker for age-related cognitive decline.
Article
Biology
Kaixin Huang, Laura K. Milton, Harry Dempsey, Stephen J. Power, Kyna-Anne Conn, Zane B. Andrews, Claire J. Foldi
Summary: Anorexia nervosa is a psychiatric disorder with a high mortality rate. Cognitive inflexibility is associated with the disorder, but it is unclear whether it predisposes individuals to anorexia nervosa. Previous animal studies using the activity-based anorexia model have shown a link between cognitive inflexibility and pathological weight loss. However, testing flexible learning in the same animals before exposure to the activity-based anorexia model has been difficult. This study presents a fully-automated and experimenter-free touchscreen cognitive testing system for rats and examines the relationship between reversal learning and weight loss in the activity-based anorexia model. The findings provide insights into the connection between cognitive inflexibility and pathological weight loss and offer potential targets for future research on pharmacotherapies for anorexia nervosa.
Article
Endocrinology & Metabolism
Felicia Reed, Alex Reichenbach, Harry Dempsey, Rachel E. Clarke, Mathieu Mequinion, Romana Stark, Sasha Rawlinson, Claire J. Foldi, Sarah H. Lockie, Zane B. Andrews
Summary: This study reveals that hunger and the environmental context can increase food-seeking behavior, and the activity of AgRP neurons plays a crucial role in this process. Precise temporal control of AgRP neuron activity is necessary for the development of the context-induced feeding response.
MOLECULAR METABOLISM
(2023)
Article
Endocrinology & Metabolism
Wang Lok So, Jiachen Hu, Lotus Jeffs, Harry Dempsey, Sarah H. Lockie, Jeffrey M. Zigman, Romana Stark, Alex Reichenbach, Zane B. Andrews
Summary: The sensory detection of food suppresses AgRP neuronal activity, and ghrelin receptor signaling on AgRP neurons integrates energy need with external sensory cues to produce an optimal change in AgRP neural activity.
MOLECULAR METABOLISM
(2023)
Article
Biochemistry & Molecular Biology
Giovanni Pacini, Bo Ahren
Summary: Tirzepatide stimulates both insulin secretion and glucose effectiveness, with stimulation of glucose effectiveness being the prominent process to reduce glucose.
Article
Biochemistry & Molecular Biology
Si -yu Wang, Yu-zhe Zhang, Xiao-han Liu, Xue-ci Guo, Xiao-fang Wang, Feng-tong Han, Yao Zhang, Chang -lin Wang
Summary: In the formalin pain test, the EM-2 analogs EM-2-Me, EM-2-Et, and EM-2-Bu showed significant analgesic effects with reduced tolerance and gastrointestinal side effects. These effects were mediated through central opioid mechanisms, with EM-2-Me possibly involving dynorphin A release and EM-2-Bu directly activating multiple opioid receptors.