Neuroendocrine control of satiation

Eating is a simple behavior with complex functions. The unconscious neuroendocrine process that stops eating and brings a meal to its end is called satiation. Energy homeostasis is mediated accomplished through the control of meal size via satiation. It involves neural integrations of phasic negative-feedback signals related to ingested food and tonic signals, such as those related to adipose tissue mass. Energy homeostasis is accomplished through adjustments in meal size brought about by changes in these satiation signals. The best understood meal-derived satiation signals arise from gastrointestinal nutrient sensing. Gastrointestinal hormones secreted during the meal, including cholecystokinin, glucagon-like peptide 1, and PYY, mediate most of these. Other physiological signals arise from activation of metabolic-sensing neurons, mainly in the hypothalamus and caudal brainstem. We review both classes of satiation signal and their integration in the brain, including their processing by melanocortin, neuropeptide Y/agouti-related peptide, serotonin, noradrenaline, and oxytocin neurons. Our review is not comprehensive; rather, we discuss only what we consider the best-understood mechanisms of satiation, with a special focus on normally operating physiological mechanism

Ectopic Hepatic Tissue Presented as a Posterior Mediastinal Mass

We present a young patient with respiratory complaints that was found to have a mass in her right posterior mediastinum. The mass was diagnosed to be ectopic histologically unremarkable hepatic tissue. We have also reviewed several of the few intrathoracic ectopic liver cases in the literature, along with a brief discussion of the significance of such a finding

Eccrine porocarcinoma of the lower extremity: A case report and review of literature

Eccrine porocarcinoma is a rare malignancy of the eccrine sweat gland. It is usually found frequently on the lower extremities, and it affects both sexes equally usually in the sixth to seventh decade. In our case, we present a 42-year-old male patient with a recurring exophytic tumor on the right lower extremity without local extension. The initial tumor was biopsied, excised and diagnosed as an eccrine poroma. The tumor then recurred 6 years later, was re-excised, reconstructed with a soleus muscle flap and diagnosed as an eccrine porocarcinoma

Ovariectomy and overeating palatable, energy-dense food increase subcutaneous adipose tissue more than intra-abdominal adipose tissue in rats

Both ovariectomy in rats and menopause are associated with increased TAT. After ovariectomy, fat is preferentially deposited as SAT and lean body mass increases, whereas after menopause fat is preferentially deposited as IAAT and lean body mass decreases. These opposite effects of ovariectomy and menopause on regional AT distribution and lean body mass indicate that ovariectomy in rats is not a homologous model of menopause-associated changes in body composition that should be used with great caution in investigations of adiposity-related diseases

Identifying and prioritizing fifth-generation wireless mobile communications (5G) applications in smart manufacturing

The fifth-generation networks of smart manufacturing and smart factory is rapidly evolving as a technology that integrates industrial production and smart Internet, bringing new support for the digital transformation of the industry and the development of a high-quality economy. Therefore, this article, with emphasis on the fifth generation of the Internet and with the aim of identifying 5G-based intelligent manufacturing projects, seeks to prioritize these projects using the hierarchical analysis method. Therefore, after reviewing the literature and interviewing with 17 experts, 5 main criteria for project prioritization were selected and weighted by AHP method using an expert questionnaire. Then, using the opinions of experts, 22 identified smart factory projects were prioritized according to the criteria weight. The criteria were calculated according to the income, cost and risk level of the project. Also Intelligent production line, intelligent logistics, intelligent resource allocation and process automation were identified as the most important intelligent production projects

Sex-Specific Gene-by-Vitamin D Interactions Regulate Susceptibility to Central Nervous System Autoimmunity

Vitamin D3 (VitD) insufficiency is postulated to represent a major modifiable risk factor for multiple sclerosis (MS). While low VitD levels strongly correlate with higher MS risk in white populations, this is not the case for other ethnic groups, suggesting the existence of a genetic component. Moreover, VitD supplementation studies in MS so far have not shown a consistent benefit. We sought to determine whether direct manipulation of VitD levels modulates central nervous system autoimmune disease in a sex-by-genotype-dependent manner. To this end, we used a dietary model of VitD modulation, together with the autoimmune animal model of MS, experimental autoimmune encephalomyelitis (EAE). To assess the impact of genotype-by-VitD interactions on EAE susceptibility, we utilized a chromosome substitution (consomic) mouse model that incorporates the genetic diversity of wild-derived PWD/PhJ mice. High VitD was protective in EAE in female, but not male C57BL/6J (B6) mice, and had no effect in EAE-resistant PWD/PhJ (PWD) mice. EAE protection was accompanied by sex- and genotype-specific suppression of proinflammatory transcriptional programs in CD4 T effector cells, but not CD4 regulatory T cells. Decreased expression of proinflammatory genes was observed with high VitD in female CD4 T effector cells, specifically implicating a key role of MHC class II genes, interferon gamma, and Th1 cell-mediated neuroinflammation. In consomic strains, effects of VitD on EAE were also sex- and genotype dependent, whereby high VitD: (1) was protective, (2) had no effect, and (3) unexpectedly had disease-exacerbating effects. Systemic levels of 25(OH)D differed across consomic strains, with higher levels associated with EAE protection only in females. Analysis of expression of key known VitD metabolism genes between B6 and PWD mice revealed that their expression is genetically determined and sex specific and implicated Cyp27b1 and Vdr as candidate genes responsible for differential EAE responses to VitD modulation. Taken together, our results support the observation that the association between VitD status and MS susceptibility is genotype dependent and suggest that the outcome of VitD status in MS is determined by gene-by-sex interactions

Comparative effects of intraduodenal amino acid infusions on food intake and gut hormone release in healthy males

In contrast to the many studies of the effects of individual amino acids (AAs) on eating, no studies have compared the effects of different AAs on eating and underlying preabsorptive gastrointestinal mechanisms. To compare the effects of intraduodenal infusions of l-tryptophan (TRP), l-leucine (LEU), l-phenylalanine (PHE) and l-glutamine (GLN) on appetite, gastrointestinal hormone responses (including ghrelin, cholecystokinin (CCK), peptide YY (PYY) and glucagon-like peptide-1 [GLP-1]), glycemia (glucagon, insulin and glucose) and test meal size in healthy males, we retrospectively analyzed data from four published independent, randomized, double-blind, placebo-controlled studies of 90-min intraduodenal infusions of the individual AAs. The designs of the studies were identical, except the dose of TRP (0.15 kcal/min) was lower than that of the other AAs (0.45 kcal/min) because higher doses of this AA were not well tolerated. TRP and LEU decreased intake more than PHE (reductions relative to control, ~219 ± 68, ~170 ± 48 and ~12 ± 57 kcal, respectively), and TRP decreased intake more than GLN (~31 ± 82 kcal). These effects of TRP and LEU versus GLN, but not versus PHE, were paralleled by greater decreases in plasma ghrelin, and increases in CCK, concentrations. TRP increased PYY more than GLN or LEU, but not PHE. LEU increased PYY less than PHE. No significant differences were detected for GLP-1. PHE increased glucagon more than TRP or LEU, and increased insulin more than TRP. Under our experimental conditions, intraduodenal TRP and LEU were more satiating than PHE and GLN. The greater satiating efficacy of LEU versus PHE was significantly dissociated from the effects of these AAs on PYY, while the greater satiating potency of TRP versus PHE was significantly dissociated from the effects of these AAs on insulin and glucagon. In contrast, ghrelin and CCK, and potentially other mechanisms, including central sensing of individual AAs, appear to be stronger candidate mechanisms for the relative satiating effects obtained.Robert E. Steinert, Sina S. Ullrich, Nori Geary, Lori Asarian, Marco Bueter, Michael Horowitz, Christine Feinle-Bisse

Polyphenic trait promotes liver cancer in a model of epigenetic instability in mice.

Hepatocellular carcinoma (HCC) represents the fifth-most common form of cancer worldwide and carries a high mortality rate attributed to lack of effective treatment. Males are 8 times more likely to develop HCC than females, an effect largely driven by sex hormones, albeit through still poorly understood mechanisms. We previously identified TRIM28 (tripartite protein 28), a scaffold protein capable of recruiting a number of chromatin modifiers, as a crucial mediator of sexual dimorphism in the liver. Trim28(hep-/-) mice display sex-specific transcriptional deregulation of a wide range of bile and steroid metabolism genes and development of liver adenomas in males. We now demonstrate that obesity and aging precipitate alterations of TRIM28-dependent transcriptional dynamics, leading to a metabolic infection state responsible for highly penetrant male-restricted hepatic carcinogenesis. Molecular analyses implicate aberrant androgen receptor stimulation, biliary acid disturbances, and altered responses to gut microbiota in the pathogenesis of Trim28(hep-/-) -associated HCC. Correspondingly, androgen deprivation markedly attenuates the frequency and severity of tumors, and raising animals under axenic conditions completely abrogates their abnormal phenotype, even upon high-fat diet challenge. This work underpins how discrete polyphenic traits in epigenetically metastable conditions can contribute to a cancer-prone state and more broadly provides new evidence linking hormonal imbalances, metabolic disturbances, gut microbiota, and cancer. (Hepatology 2017;66:235-251)

Changes in PYY and gastric emptying across the phases of the menstrual cycle and the influence of the ovarian hormones

Nutrition-related studies avoid the participation of pre-menopausal women due to the potential effect of the menstrual cycle (MC) on their appetite regulation. It is generally accepted that women increase their energy intake during the luteal phase (LPh) compared to the follicular (FPh), however what happens in the menstrual phase (MPh) and how this might be regulated remains uncertain. Although some research indicates changes in the gastric emptying (GE) velocity, whether PYY is affected by the MC phase, remains unknown. The aim of this study was to assess whether eating the same breakfast in each of the three MC phases would change the GE time, the PYY response and post-prandial satiety such that they might affect subsequent food intake. Furthermore, the aim was to associate any potential differences to the fluctuations in estradiol (E2) and progesterone (P4) within a MC. Nine naturally cycling women attended to the laboratory to consume a standardised breakfast on three occasions, each of them representing one of the MC phases. Breath samples to measure GE time, plasma samples to quantify PYY levels and hunger scores were collected for a total of 4 h after which food intake was assessed by an ad-libitum buffet lunch. GE and PYY levels changed significantly across the phases of the MC (p < 0.05). GE was correlated to P4 and E2-P4 ratio (r = -0.5 and 0.4, respectively). To conclude, the appetite regulators PYY and GE time change depending upon the MC phases with GE time associated with the ovarian hormone levels which suggests the necessity of controlling the MC phase in studies looking at the appetite response