Acyl ghrelin, a 28-amino acid peptide hormone, is the endogenous cognate ligand for the growth hormone secretagogue receptor. Ghrelin is involved in stimulating growth hormone release, eliciting feeding behavior, inducing adiposity and stimulating gastrointestinal motility. Ghrelin is unique for its post-translational modification of O-n-octanoylation at serine 3 through ghrelin O-acyltransferase, and is the only peripheral signal to enhance food intake. Plasma ghrelin levels manifest "biphasic changes" in diabetes mellitus (DM). In the early stage of DM, the stomach significantly increases the secretion of ghrelin into the plasma, and elevated plasma ghrelin levels are correlated with diabetic hyperphagic feeding and accelerated gastrointestinal motility. In the late stage of DM, plasma ghrelin levels may be lower, which might be linked with anorexia/muscle wasting, delayed gastrointestinal transit, and even gastroparesis. Therefore, the unique ghrelin system may be the most important player compared to the other hindgut hormones participating in the "entero-insular axis". Further studies using either knockdown or knockout of ghrelin gene products and ghrelin O-acyltransferase may unravel the pathogenesis of DM, and show benefits in combating this disease and metabolic syndrome.

Human ghrelin and human motilin, belonging to the ghrelin/motilin-related peptide family, share 36% amino acid sequence identity, while the human ghrelin receptor exhibits a remarkable 50% overall identity with the human motilin receptor. In addition to their structural resemblance, ghrelin and motilin are the only two mammalian hormones known to decrease in the postprandial period. Ghrelin and motilin participate in initiating the migrating motor complex in the stomach, and stimulate gastrointestinal motility, accelerate gastric emptying, and induce “gastric hunger”. In addition to modulating the release of growth hormone and gut motility, ghrelin plays a crucial role in the secretion and protection of the stomach and colon. Ghrelin mimetics and motilin agonists are currently being developed to reverse gastrointestinal hypomotility disorders. With additional appetite-enhancing, adiposity-promoting, and anti-inflammatory effects, ghrelin and rikkunshito (a traditional Japanese herb enhancing acyl ghrelin signaling) are superior to motilin in the treatment of cancerrelated anorexia and cachexia, post-chemotherapy symptoms, rheumatological diseases, age-related frailty, as well as post-operative, septic, and post-burn gut ileus.

To investigate the effects of hydrogen-rich water (HRW) treatment on prevention of ethanol (EtOH)-induced early fatty liver in mice. In vitro reduction of hydrogen peroxide by HRW was determined with a chemiluminescence system. Female mice were randomly divided into five groups: control, EtOH, EtOH + silymarin, EtOH + HRW and EtOH + silymarin + HRW. Each group was fed a Lieber-DeCarli liquid diet containing EtOH or isocaloric maltose dextrin (control diet). Silymarin was used as a positive control to compare HRW efficacy against chronic EtOH-induced hepatotoxicity. HRW was freshly prepared and given at a dosage of 1.2 mL/mouse trice daily. Blood and liver tissue were collected after chronic-binge liquid-diet feeding for 12 wk. The in vitro study showed that HRW directly scavenged hydrogen peroxide. The in vivo study showed that HRW increased expression of acyl ghrelin, which was correlated with food intake. HRW treatment significantly reduced EtOH-induced increases in serum alanine aminotransferase, aspartate aminotransferase, triglycerol and total cholesterol levels, hepatic lipid accumulation and inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6. HRW attenuated malondialdehyde level, restored glutathione depletion and increased superoxide dismutase, glutathione peroxidase and catalase activities in the liver. Moreover, HRW reduced TNF-α and IL-6 levels but increased IL-10 and IL-22 levels. HRW protects against chronic EtOH-induced liver injury, possibly by inducing acyl ghrelin to suppress the pro-inflammatory cytokines TNF-α and IL-6 and induce IL-10 and IL-22, thus activating antioxidant enzymes against oxidative stress.

Objective. Rheumatoid arthritis (RA) is a chronic inflammatory disease that damages the synovial joints, and patients with it are often anorexic and cachectic with high morbidity and mortality. Biological therapy with anti-tumor necrosis factor (TNF)-α has been proven effective as a treatment for RA. However, the long-term effects of anti-TNF-α therapy on body weight, appetite, plasma gut hormones and leptin have not been investigated. Methods. Twenty RA patients received subcutaneous injections of etanercept, a chimeric protein of human IgG1 Fc and TNF receptor p75, twice weekly for 12 consecutive months. Sequential changes in body weight, body fat, appetite rating, lipid profiles, gut hormones and leptin were measured at baseline and at 3 and 12 months after treatment. Ten RA patients who received non-biological disease modifying anti-rheumatic drugs were enrolled as the controls and were appraised at baseline and at 12 months after treatment (a nonrandomized study). Results. Significant weight gain, hyperuricemia, decreased fasting plasma glucose-dependent insulinotropic polypeptide (GIP) levels, and loss of post-oral glucose suppression of plasma leptin concentration were found in the patients after the 12-month course of etanercept therapy, but not in the controls. A transient decrease in fasting plasma acyl ghrelin occurred at 3 months during etanercept treatment. Appetite score and serum lipid profiles did not change in either group. Conclusion. Long-term therapy with anti-TNF-α is promising in ameliorating body mass decrease in patients with active RA. Plasma levels of ghrelin, GIP and leptin may play significant roles in maintaining energy homeostasis in the anti-inflammatory responses during RA remission.

Background: Sleeve gastrectomy (SG) is an effective treatment for obesity and type 2 diabetes mellitus (T2DM), and non-alcoholic fatty liver disease (NAFLD); however, the mechanism is not completely understood. Bile acids and fibroblast growth factors (FGFs) are involved in the regulation of energy metabolism. Methods: We investigated the roles of total bile acid and FGF 19 in T2DM remission and NAFLD improvement in obese subjects undergoing SG. A total of 18 patients with obesity and T2DM undergoing laparoscopic SG were enrolled in this study. Serial plasma total bile acid and FGF 19 levels were measured, while the fatty liver index was calculated before and after surgery. Results: The FGF 19 level significantly increased, and the total bile acid level and fatty liver index decreased 1 year after surgery. The complete T2DM remission rate was 66.7% one year after surgery; the complete remitters had significantly lower FGF 19 levels and higher insulin levels than the non-complete remitters. The complete remitters also had significantly decreased total bile acid levels and increased FGF 19 levels 1 year after surgery compared with those before surgery. The fatty improvers had significantly decreased total bile acid levels and increased FGF 19 levels 1 year after surgery compared with those before surgery. Conclusion: The total bile acids level and fatty liver index decreased, and the FGF 19 levels increased 1 year after SG. Both T2DM complete remitters and NAFLD improvers showed significantly decreased total bile acid levels and increased FGF 19 levels 1 year after SG. Plasma total bile acids and FGF 19 might have roles in T2DM remission and NAFLD improvement. Low preoperative FGF 19 levels might be a predictor for NAFLD improvement after SG.

Previous studies have reported the positive effects of branched-chain amino acids (BCAAs) supplementation on lowering plasma markers of muscle damage and subjective soreness after resistance exercise. However, a variety of factors can potentially moderate its efficacy. This meta-analysis aimed to summarize the evidence regarding the effect of BCAAs supplementation on plasma muscle damage markers and soreness after resistance exercise in only trained males, by considering the plasma lactate dehydrogenase (LDH) and creatine kinase (CK). Randomized controlled trials were identified through a computerized literature search for the period 2010–2020. The pooled data were analyzed with the random-effects model and heterogeneity using I². Cochrane Collaboration tools was used for the assessment of risk of bias. Nine studies met the inclusion criteria. A positive effect was found for CK at <24, 24, and 48 h after exercise and for muscle soreness at <24 h only. However, the positive effect was not evident for plasma LDH at any follow-up time. Different outcomes for post-exercise responses may suggest that BCAAs supplementation can attenuate muscle damage and ameliorate muscle soreness after resistance exercise in trained males.