Shilpa Gaidhane

Ghrelin: Ghrelin as a Regulatory Peptide in Growth Hormone Secretion

BACKGROUND Ghrelin is a type of growth hormone (GH) secretagogue that stimulates the release of GH. It is a first hormone linking gastrointestinal-pituitary axis. OBJECTIVE This review highlights the interaction of ghrelin with GHRH and somatostatin to regulate the secretion of GH and intends to explore the possible physiological role of the ghrelin-pituitary-GH axis linkage system. OBSERVATION Ghrelin is highly conserved among species and is classified into octanoylated (C8:0), decanoylated (C10:0), decenoylated (C10:1) and nonacylated,ghrelin. Acylated ghrelin is the major active form of human ghrelin. The primary production site of ghrelin is the stomach, and it interacts with stomach ghrelin as well as hypothalamic GHRH and somatostatin in the regulation of pituitary GH secretion. Ghrelin stimulate GH release through the GHS receptor to increase intracellular Ca2+ ([Ca2+] levels via IP3 signal transduction pathway. Ghrelin is a specific endogenous ligand for the GHS receptor and provides a definitive proof of the occurance of a GHS-GHS receptor signalling system in the regulation of GH secretion. CONCLUSION Studies suggests that ghrelin is a powerful pharmacological agent that exerts a potent, time-dependent stimulation of pulsatile secretion of GH.

Effect of Ghrelin on Mortality and Cardiovascular Outcomes in Experimental Rat and Mice Models of Heart Failure: A Systematic Review and Meta-Analysis

Background Heart failure (HF) continues to be a challenging condition in terms of prevention and management of the disease. Studies have demonstrated various cardio-protective effects of Ghrelin. The aim of the study is to determine the effect of Ghrelin on mortality and cardiac function in experimental rats/mice models of HF. Methods Data sources: PUBMED, Scopus. We searched the Digital Dissertations and conference proceedings on Web of Science. Search methods: We systematically searched for all controlled trials (upto November 2014) which assessed the effects of Ghrelin (irrespective of dose, form, frequency, duration and route of administration) on mortality and cardiac function in rats/ mice models of HF. Ghrelin administration irrespective of dose, form, frequency, duration and route of administration. Data collection and analysis: Two authors independently assessed each abstract for eligibility and extracted data on characteristics of the experimental model used, intervention and outcome measures. We assessed the methodological quality by SYRCLE’s risk of bias tool for all studies and the quality of evidence by GRADEpro. We performed meta-analysis using RevMan 5.3. Results A total of 325 animals (rats and mice) were analyzed across seven studies. The meta-analysis revealed that the mortality in Ghrelin group was 31.1% and in control group was 40% (RR 0.83, 95% CI 0.46 to 1.47) i.e Ghrelin group had 68 fewer deaths per 1000 (from 216 fewer to 188 more) as compared to the control group. The meta-analysis reveals that the heart rate in rats/mice on Ghrelin was higher (MD 13.11, 95% CI 1.14 to 25.08, P=0.66) while the mean arterial blood pressure (MD -1.38, 95% CI -5.16 to 2.41, P=0.48) and left ventricular end diastolic pressure (MD -2.45, 95% CI -4.46 to -0.43, P=0.02) were lower as compared to the those on placebo. There were insignificant changes in cardiac output (SMD 0.28, 95% CI -0.24 to 0.80, P=0.29) and left ventricular end systolic pressure (MD 1.48, 95% CI -3.86 to 6.82, P=0.59). Conclusions The existing data provides evidence to suggest that Ghrelin may lower the risk of mortality and improve cardiovascular outcomes. However; the quality of evidence as assessed by GRADEpro is low to very low. Clinical judgments to administer Ghrelin to patients with HF must be made on better designed animal studies.

Ghrelin O Acyl Transferase (GOAT) as a Novel Metabolic Regulatory Enzyme

BACKGROUND Obesity and Type 2 Diabetes Mellitus (T2DM) presents a growing threat to the global health. Evidences highlight an important role of ghrelin as a key regulator of glucose metabolism. The physiological functions of ghrelin are mediated by enzyme ghrelin-O-acyltransferase (GOAT) which is capable of generating the active form of this metabolic hormone. However, its exact mechanism of action and influence on energy balance and glucose metabolism is yet to be explored. OBJECTIVES To review the physiological role of GOAT in the regulation of energy balance and glucose metabolism and explore the potential therapeutic avenues of modulators of GOAT to counter the progression of obesity and T2DM. METHODS Publications were sought through electronic searches. The bibliographies of all papers, book, chapters and editorials were scanned and hand searches were also conducted for journals, and conference proceedings. CONCLUSION GOAT peptide modulates the insulin secretion as well as insulin sensitivity. Modulators of GOAT signaling like inhibitors of GOAT increases insulin secretion, enhance peripheral insulin sensitivity and thus counters obesity and T2DM. Modulators of GOAT can be a probable therapy for modifying food intake and for countering obesity and T2DM.

Somatotropic and cardio-protective effects of ghrelin in experimental models of heart failure: A systematic review

Background: Ghrelin was initially recognized as an endogenous ligand of growth hormone secretagogue receptor and was implicated in the regulation of food intake, and promoting weight gain. Ghrelin has been shown to improve cardiac function in patients suffering from heart failure (HF) though various mechanisms. The aim of the review is to summarize the main findings in this field, with the purpose of promoting further studies on the role of ghrelin on the cardiovascular system. Materials and Methods: All publications describing trials, systematic reviews, meta-analyses and review papers published within 1999-2014 of ghrelin in animal models of HF were sought through electronic and manual searches. Results: The literature searches identified 126 references and ten trials meeting the inclusion criteria were included in this review. All studies were carried out on male rats and experimental model of HF. Ghrelin has been shown to reduce mortality, increase appetite and body weight, and was found to improve the cardiac function parameters. Review found deficient information about adverse effects of ghrelin. Ghrelin exerts cardioprotective effects through modulation of sympathetic nervous system, inhibiting autophagy, antiinflammatory effects and protection against ischemia/reperfusion injury. Conclusion: Ghrelin seems to have a beneficial effect in rat models of HF and can offer an effective therapeutic target for improving outcome in HF.

Ghrelin as a Promising Therapeutic Option for Cancer Cachexia

Cachexia is a devastating complication of cancer and an important cause of morbidity and mortality and can have a great effect on quality of life, and sense of self-esteem. Unfortunately; there is no standard cure available for cancer cachexia. Ghrelin; a 28 amino acid orexigenic gut hormone and its mimetics have shown potential benefits in reversing the breakdown of protein and weight loss in catabolic states like cancer cachexia. Ghrelin has effects on several vital pathways in the regulation of appetite, and composition of the body. It increases the secretion of growth hormone and reduces energy expenditure. It plays an important role in regulation of processes associated with cancer and antagonizing protein breakdown in catabolic conditions such as cancer cachexia. Additionally, ghrelin has anti-inflammatory, anti-apoptotic and anxiolytic effects. Administration of ghrelin for short-term has been found to be well-tolerated and safe. These versatile actions of ghrelin and its safety can render it as a potentially useful novel therapy for patients with cancer cachexia. However; there is a need to generate more evidence to support the use of ghrelin in the management of cancer cachexia.

Risk factor of type 2 diabetes mellitus among adolescents from rural area of India

Context: Health system is likely to encounter more adolescents with Type 2 diabetes mellitus (T2DM) as a consequence of obesity and sedentary lifestyle. Intervention at various stages of the life cycle is needed as cumulative effect of risk factors accumulated from fetal life to adult increases risk of noncommunicable disease. Aims: The aim of this study was to find out awareness regarding T2DM and distribution of risk factor for T2DM in adolescents from the rural areas of Wardha district, India. Methodology: A cross-sectional study conducted in the rural area of India involves 412 adolescent boys and girls selected by systematic random sampling technique. Data collected by a face-to-face interview and waist-hip ratio (WHR), body mass index, random capillary blood glucose (RCBG) were estimated. Results: 65.1% were aware of T2DM. Girls, older adolescents, higher education were associated with awareness (P < 0.001). Totally, 204 (49.51%) had some risk factors for T2DM, of these 191 (46.6%) had sedentary lifestyle, 153 (31.7%) adolescents had nutritional risk factors, 69 (43.4%) boys had WHR >0.90 and 113 (71.1%) girls had WHR >0.85, 103 (25%) adolescents had RCBG ≥110 mg/dl, and 77 (18.7%) participants reported family history of DM. Conclusions: Considering the risk factors of T2DM among adolescents from the rural area, there is a need for prevention programs for creating awareness related to T2DM, early identification of risk factor for T2DM, and targeted interventions. The study may serve as a formative research for developing and testing interventions aimed at primary prevention of T2DM among adolescents from rural India.

Challenges and Patterns of Complementary Feeding for Women In Employment: A Qualita-tive Study from Rural India

Timely initiation of complementary feeding and pattern of complementary feeding is suboptimal in India. Women in employment faces challenges for following optimum Infant and Young Child Feeding practices, which have a significant impact on growth and development of child under 2 years of age. Objective was to study challenges faced by women in employment for complementary feeding and pattern of complementary feeding in rural area. Qualitative study was conducted in rural area of Wardha district, India. Six FGDs were conducted and participants (total 39) were women in employment having child between 6-23 months and community level service providers. Women in rural area resume work early, could not practice exclusive breast feeding for six months. They initiate complementary feeding early and had inadequate awareness regarding complementary feeding. Women initiate semisolid and soft food at 4-6 months, smashed solid food at 7-9 months. Women leave their babies at mercy of the elders or sometime neighbours when they are at work. Villages do not have child care facilities or creches. All these determinants compromises complementary feeding with regards to timely and adequacy, recommended dietary diversity, safe feeding. Challenges for practicing exclusive breast feeding for 6 month, early initiation and inadequate complementary feeding adversely affect growth and development of children in rural area which may have undesired long term implication on the cognitive development. Strengthening Anganwadi program in India with more focus on children under 2 years, community baby care rooms / creches services would be useful strategy for supporting the women in employment to practice the optimum IYCF recommendations. India needs a conducive workplace policies and adequate protection by law for women in employment.