Shedding light on the intricate puzzle of ghrelin's effects on appetite regulation

Kola, Blerina; Korbonits, Márta

doi:10.1677/joe-09-0056

Cited by 44 publications

(37 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The fatty acid pathways (Lopez et al, 2008) and mitochondrial uncoupling protein 2 (UCP2) (Andrews et al, 2008), have been identified as novel downstream effectors. Combining the recently described data, a pathway by which ghrelin could stimulate appetite has been suggested (Kola & Korbonits, 2009) (Figure 1). …”

Section: Both Havementioning

confidence: 85%

Ghrelin in obesity and endocrine diseases

Scerif

Goldstone

Korbonits

2011

Molecular and Cellular Endocrinology

Self Cite

View full text Add to dashboard Cite

Section: Both Havementioning

confidence: 85%

Ghrelin in obesity and endocrine diseases

Scerif

Goldstone

Korbonits

2011

Molecular and Cellular Endocrinology

Self Cite

View full text Add to dashboard Cite

“…These results indicate that ghrelin increases the expression and secretion of VEGF 120 and MCP-1, but not through the induction of oxidative or ER stress (Miyokawa-Gorin et al, 2012), on the peripheral adipocytes. Ghrelin decreases AMPK activity in white adipose tissue, while it increases the AMPK activity in the hypothalamus and heart (Andersson et al, 2004;Kola et al, 2005;Kola and Korbonits, 2009;Zhang et al, 2009). Thus, we measured the changes on the ghrelin-stimulated AMPK activity in the adipocytes.…”

Section: Discussionmentioning

confidence: 99%

Ghrelin Augments the Expressions and Secretions of Proinflammatory Adipokines, VEGF₁₂₀ and MCP‐1, in Differentiated 3T3‐L1 Adipocytes

Kitahara

Takahashi

Moriya

et al. 2014

Journal Cellular Physiology

View full text Add to dashboard Cite

Ghrelin is a physiological-active peptide with growth hormone-releasing activity, orexigenic activity, etc. In addition, the recent study has also suggested that ghrelin possesses the pathophysiological abilities related to type 2 diabetes. However, the ghrelin-direct-effects implicated in type 2 diabetes on peripheral tissues have been still unclear, whereas its actions on the central nervous system (CNS) appear to induce the development of diabetes. Thus, to assess its peripheral effects correlated with diabetes, we investigated the regulatory mechanisms about adipokines, which play a central role in inducing peripheral insulin resistance, secreted from mature 3T3-L1 adipocytes stimulated with ghrelin in vitro. The stimulation with 50 nmol/L ghrelin for 24 h resulted in the significant 1.9-fold increase on vascular endothelial growth factor-120 (VEGF 120 ) releases (P < 0.01) and the 1.7-fold on monocyte chemoattractant protein-1 (MCP-1) (P < 0.01) from 3T3-L1 adipocytes, respectively, while ghrelin failed to enhance tumor necrosis factor-a (TNF-a), interleukin-1b (IL-1b), IL-6, IL-10 and adiponectin secretions. In addition, Akt phosphorylation on Ser473 and c-Jun NH 2 -terminal protein kinase (JNK) phosphorylation on Thr183/Tyr185 were markedly enhanced 1.4-fold (P < 0.01) and 1.6-fold (P < 0.01) in the ghrelin-stimulated adipocytes, respectively. Furthermore, the treatment with LY294002 (50 mmol/L) and Wortmannin (10nmol/L), inhibitors of phosphatidylinositol 3-kinase (PI3K), significantly decreased the amplified VEGF 120 secretion by 29% (P < 0.01) and 28% (P < 0.01) relative to the cells stimulated by ghrelin alone, respectively, whereas these inhibitors had no effects on increased MCP-1 release. On the other hand, JNK inhibitor SP600125 (10 mmol/L) clearly reduced the increased MCP-1, but not VEGF 120 , release by 35% relative to the only ghrelin-stimulated cells (P < 0.01). In conclusion, ghrelin can enhance the secretions of proinflammatory adipokines, VEGF 120 and MCP-1, but fails to affect IL-10 and adiponectin which are considered to be anti-inflammatory adipokines. Moreover, this augmented VEGF 120 release is invited through the activation of PI3K pathways and the MCP-1 is through JNK pathways. Consequently, our results strongly suggest that ghrelin can induce the development of diabetes via its direct-action in peripheral tissues, as well as, via CNS.

show abstract

“…Orexigenic signals act via adenosine monophosphate-activated protein kinase (AMPK) and increase the dopaminergic transmission from the ventral tegmental area to the nucleus accumbens, enhancing the reward signals. 40 Therefore, the binding of ghrelin to its specific receptor GHSR1a will lead to an increase in intracellular calcium concentration, with consequent activation of CaMKK2 (calmodulin kinase-kinase 2), which will phosphorylate AMPK. 41 In its turn, AMPK will phosphorylate and inhibit acetyl-coenzyme A carboxylase, resulting in decreased levels of malonyl-CoA and subsequent activation of carnitine-palmitoyltransferase-1.…”

Section: Ghrelin -A Peripheral Orexigenic Peptide With Central Actionmentioning

confidence: 99%

Effects of ghrelin in energy balance and body weight homeostasis

Mihalache¹,

Gherasim²,

Niţă³

et al. 2016

View full text Add to dashboard Cite

ghrelin is a gut peptide composed of 28 amino acids mostly secreted in the gastric fundus mucosa. It was isolated and described in 1999 by Kojima et al. and only three years later its specific receptor, ghsR1a, was also identified. ghrelin, the endogenous ligand for the gh secretagogue receptor, is the only peripheral orexigenic hormone that activates the receptors to be found especially in the appetite center (hypothalamus and pituitary gland). ghrelin is present in human plasma in two forms: an inactive form known as deacylated ghrelin, and an active form called acylated ghrelin synthesized under the action of ghrelin O-acyltransferase enzyme (gOAT). The literature even mentions an extremely complex ghrelin/gOAT/ghsR system involved in the regulation of human energy, metabolism and adaptation of energy homeostasis to environmental changes. In humans, there is a preprandial rise and a postprandial fall in plasma ghrelin levels, which strongly suggest that the peptide plays a physiological role in meal initiation and may be employed in determining the amount and quality of ingested food. Besides the stimulation of food intake, ghrelin determines a decrease in energy expenditure and promotes the storage of fatty acids in adipocytes. Thus, in the human body ghrelin induces a positive energy balance, an increased adiposity gain, as well as an increase in caloric storage, seen as an adaptive mechanism to caloric restriction conditions. In the current world context, when we are witnessing an increasing availability of food and a reduction of energy expenditure to a minimum level, these mechanisms have become pathogenic. As a consequence, the hypothesis that ghrelin is involved in the current obesity epidemic has been embraced by many scholars and researchers

show abstract

Shedding light on the intricate puzzle of ghrelin's effects on appetite regulation

Cited by 44 publications

References 52 publications

Ghrelin in obesity and endocrine diseases

Ghrelin in obesity and endocrine diseases

Ghrelin Augments the Expressions and Secretions of Proinflammatory Adipokines, VEGF₁₂₀ and MCP‐1, in Differentiated 3T3‐L1 Adipocytes

Effects of ghrelin in energy balance and body weight homeostasis

Contact Info

Product

Resources

About

Shedding light on the intricate puzzle of ghrelin's effects on appetite regulation

Cited by 44 publications

References 52 publications

Ghrelin in obesity and endocrine diseases

Ghrelin in obesity and endocrine diseases

Ghrelin Augments the Expressions and Secretions of Proinflammatory Adipokines, VEGF120 and MCP‐1, in Differentiated 3T3‐L1 Adipocytes

Effects of ghrelin in energy balance and body weight homeostasis

Contact Info

Product

Resources

About

Ghrelin Augments the Expressions and Secretions of Proinflammatory Adipokines, VEGF₁₂₀ and MCP‐1, in Differentiated 3T3‐L1 Adipocytes