Development of abdominal aortic aneurysm is decreased in mice with plasma phospholipid transfer protein deficiency.

Plasma phospholipid transfer protein (PLTP) increases the circulating levels of proatherogenic lipoproteins, accelerates blood coagulation, and modulates inflammation. The role of PLTP in the development of abdominal aortic aneurysm (AAA) was investigated by using either a combination of mechanical and elastase injury at one site of mouse aorta (elastase model) or continuous infusion of angiotensin II in hyperlipidemic ApoE-knockout mice (Ang II model). With the elastase model, complete PLTP deficiency was associated with a significantly lower incidence and a lesser degree of AAA expansion. With the Ang II model, findings were consistent with those in the elastase model, with a lower severity grade in PLTP-deficient mice, an intermediate phenotype in PLTP-deficient heterozygotes, and a blunted effect of the PLTP-deficient trait when restricted to bone marrow-derived immune cells. The protective effect of whole-body PLTP deficiency in AAA was illustrated further by a lesser degree of adventitia expansion, reduced elastin degradation, fewer recruited macrophages, and less smooth muscle cell depletion in PLTP-deficient than in wild-type mice, as evident from comparative microscopic analysis of aorta sections. Finally, cumulative evidence supports the association of PLTP deficiency with reduced expression and activity levels of matrix metalloproteinases, known to degrade elastin and collagen. We conclude that PLTP can play a significant role in the pathophysiology of AAA.

Different ghrelin localisation in adult human and rat endocrine pancreas.

Ghrelin is an endocrine peptide that has been identified in gastric oxyntic glands and that induces growth hormone secretion in the pituitary gland. This growth hormone secretagogue is expressed in many tissues such as stomach, pituitary gland, thyroid, testis, placenta and pancreas. Initial studies of ghrelin focused on its role as a circulating orexigenic signal. However, ghrelin has also been found to be involved in the modulation of glucose homeostasis. Although a number of studies have reported ghrelin expression in developing pancreas, the location of ghrelin-immunoreactive cells in adult pancreas (epsilon cells) remains controversial. In this study, we have analysed the distribution of pancreatic epsilon cells in adult human and rat islets by immunohistochemistry and in situ hybridisation. In humans, our immunohistochemical analysis has shown that ghrelin is expressed in glucagon-secreting cells, whereas in rats, it is present in insulin-secreting cells. Similar observations have been revealed by in situ hybridisation.

Potentiality of ghrelin as antioxidant and protective agent.

BACKGROUND: Oxidative stress is the result of cellular troubles related to aerobic metabolism. Furthermore, this stress is always associated with biological responses evoked by physical, chemical, environmental, and psychological factors. Several studies have developed many approaches of antioxidant defense to diminish the severity of many diseases. Ghrelin was originally identified from the rat stomach, and it is a potent growth hormone-releasing peptide that has pleiotropic functions. METHODS: A systematic review was conducted within PubMed, ScienceDirect, MEDLINE, and Scopus databases using keywords such as ghrelin, antioxidant, oxidative stress, and systemic oxidative stress sensor. RESULTS: In the last decade, many studies show that ghrelin exhibits protection effects against oxidative stress derived probably from its antioxidant effects. Pieces of evidence demonstrate that systemic oxidative stress increase ghrelin levels in the plasma. The expression of ghrelin and its receptor in ghrelin peripheral tissues and extensively in the central nervous system suggests that this endogenous peptide plays an important role as a systemic oxidative stress sensor. CONCLUSION: The current evidence confirms that ghrelin and its derived peptides (Desacyl-ghrelin, obestatin) act as a protective antioxidant agent. Therefore, stressor modality, duration, and intensity are the parameters of oxidative stress that must be taken into consideration to determine the role of ghrelin, Desacyl-ghrelin, and obestatin in the regulation of cell death pathways.

Adiponectin is synthesized and secreted by human and murine cardiomyocytes.

Adiponectin is thought to play a decisive role in the relationships among obesity, insulin resistance and cardiovascular risk. This study investigated whether cardiomyocytes synthesize and secrete adiponectin, and the effects of this hormone on cardiac cells. RT-PCR showed that mouse, rat and human cardiomyocytes produced mRNA for adiponectin and adiponectin receptors 1 and 2. Immunohistochemistry confirmed the presence of adiponectin in the cytoplasm of cultured cardiomyocytes, and radioimmunoassay showed that these cells secreted adiponectin into the culture medium. Exogenous adiponectin enhanced glucose and fatty acid uptake and induced AMPK phosphorylation in cultured cardiomyocytes. Our results demonstrate that adiponectin is synthesized and secreted by isolated murine and human cardiomyocytes, and suggest that the local production of this hormone by cardiomyocytes could be involved in the regulation of cardiac metabolism and function.

Hypothalamic fatty acid metabolism mediates the orexigenic action of ghrelin.

Current evidence suggests that hypothalamic fatty acid metabolism may play a role in regulating food intake; however, confirmation that it is a physiologically relevant regulatory system of feeding is still incomplete. Here, we use pharmacological and genetic approaches to demonstrate that the physiological orexigenic response to ghrelin involves specific inhibition of fatty acid biosynthesis induced by AMP-activated protein kinase (AMPK) resulting in decreased hypothalamic levels of malonyl-CoA and increased carnitine palmitoyltransferase 1 (CPT1) activity. In addition, we also demonstrate that fasting downregulates fatty acid synthase (FAS) in a region-specific manner and that this effect is mediated by an AMPK and ghrelin-dependent mechanisms. Thus, decreasing AMPK activity in the ventromedial nucleus of the hypothalamus (VMH) is sufficient to inhibit ghrelin's effects on FAS expression and feeding. Overall, our results indicate that modulation of hypothalamic fatty acid metabolism specifically in the VMH in response to ghrelin is a physiological mechanism that controls feeding.

Ghrelin localization in rat and human thyroid and parathyroid glands and tumours.

Ghrelin, the endogenous ligand of the growth hormone secretagogue receptor (GHS-R), is a 28 amino acid peptide originally isolated from rat stomach that has been primarily involved in the central neuroregulation of GH secretion and food intake. Previous studies demonstrated that ghrelin has a widespread expression in different normal cells and tissues, as well as in gastric, thyroid, testicular, breast and lung neoplasias. In the current study, we use molecular biology to detect ghrelin transcripts expression in rats, and immunohistochemical techniques to investigate the cellular distribution of this peptide in rat and human thyroid and parathyroid glands and tumours. Ghrelin was localized in thyroid C cells and in parathyroid cells. Thyroid carcinomas (medullar, follicular and papillary) and parathyroid adenomas also showed intense and diffuse immunostaining for ghrelin. These data provide direct morphological evidence that ghrelin may well be acting in a paracrine fashion in the regulation of thyroid follicular cell function. The diffuse ghrelin immunostaining found in the parathyroid gland opens up the possibility of its secretion to the bloodstream or its involvement in the regulation of the parathyroid function. Overall, expression of ghrelin in human and rat thyroid and parathyroid glands is highly suggestive of a conserved role of this molecule in the regulation of thyroid and parathyroid cell function.