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Aims: Depression is a frequent comorbidity in patients with chronic heart failure (CHF). Telemonitoring has emerged as a novel option in CHF care. However, patients with depression have been excluded in most telemedicine studies. This pre-specified subgroup analysis of the Telemedical Interventional Monitoring in Heart Failure (TIM-HF) trial investigates the effect of telemonitoring on depressive symptoms over a period of 12 months. Methods and results: The TIM-HF study randomly assigned 710 patients with CHF to either usual care (UC) or a telemedical intervention (TM) using non-invasive devices for daily monitoring electrocardiogram, blood pressure and body weight. Depression was evaluated by the 9-item Patient Health Questionnaire (PHQ-9) with scores ���10 defining clinically relevant depressive symptoms. Mixed model repeated measures were performed to calculate changes in PHQ-9 score. Quality of life was measured by the Short Form-36. At baseline, 156 patients had a PHQ-9 score ���10 points (TM: 79, UC: 77) with a mean of 13.2 points indicating moderate depressiveness. Patients randomized to telemedicine showed an improvement of their PHQ-9 scores, whereas UC patients remained constant (P = 0.004). Quality of life parameters were improved in the TM group compared to UC. Adjustment was performed for follow-up, New York Heart Association class, medication, age, current living status, number of hospitalizations within the last 12 months and serum creatinine. In the study population without depression, the PHQ-9 score was similar at baseline and follow-up. Conclusion: Telemedical care improved depressive symptoms and had a positive influence on quality of life in patients with CHF and moderate depression.

Objective The recommendation for conventional body weight loss (BWL) treatment in obesity is 5-10%. It is not clear whether BWL is similar across the three different body mass index (BMI) obesity classes. The aim was to provide an overview on BWL across these classes in moderate lifestyle/diet intervention programs. Method A systematic literature search was conducted and the evidence of randomized controlled trials (RCTs) and pre-post design studies synthesized. The outcome was BWL. Results For RCTs, mean BWL in the intervention group was 3.6 kg (class I) and 5.3 kg (class II), which equates to 4 and 5% BWL, respectively. None of the assessed class III obesity studies met the inclusion criteria. For pre-post design studies, mean BWL was 5.4 kg (class I), 5.5 kg (class II) and 7.9 kg (class III), with high variation within and across studies in the latter. This equates to 6, 5 and, 6% BWL, respectively. Conclusions BWL of moderate BWL programs are similar across the different obesity classes. For class I obesity, the results differ between RCT and pre-post design studies by 2% BWL. The high variation of BWL in class III obesity might reflect different states of motivation such as the attitude towards bariatric surgery.

BACKGROUND Hypothalamic corticotropin-releasing factor (CRF) receptor 1 (CRF1 ) plays a role in acute stress-related stimulation of colonic motor function. Less is known on CRF1 signaling in the brainstem. METHODS We investigate CRF1 expression in the brainstem and the colonic response to 4th ventricle (4V) injection of CRF and urocortin (Ucn) 2 (3 µg/rat) in chronically cannulated male rats. KEY RESULTS Transcripts of CRF1 wild-type 1a and splice variants 1c, 1e, 1f, 1o along with three novel variants 1a-2 (desK-110 in exon 5), 1p (-exon 7), and 1q (exon 5 extension) were identified in the pons and medulla. The area postrema, nucleus tractus solitarius, dorsal motor nucleus of the vagus, locus coeruleus, and Barrington's nucleus isolated by laser capture microdissection expressed 1a, 1a-2, and 1p but not 1q. Compared to 4V vehicle, 4V CRF induced fecal pellet output (FPO) and diarrhea that were blocked by the CRF antagonist, astressin-B. CRF2 agonist, Ucn2 had no effect on basal or CRF-induced FPO. CRF actions were correlated with the induction of c-Fos immunoreactivity in myenteric neurons of the proximal and distal colon (pC, dC) and submucosal neurons of dC. c-Fos immunoreactivity occurred in 39% and 37% of myenteric cholinergic and 7% and 58% of nitrergic neurons in the pC and dC, respectively. CONCLUSIONS & INFERENCES CRF1a and its splice variants are expressed in brainstem nuclei, and activation of CRF1 signaling at the level of the brainstem stimulates colonic secretory-motor function through activation of colonic enteric neurons.

The discovery of somatostatin (SST) in the hypothalamus implicated the peptide in the inhibition of growth hormone release. However, as observed for numerous neuropeptides, SST was neither restricted to this one brain site nor to this one function. Subsequent studies established a widespread but specific expression of SST in the central nervous system of rodents and humans along with the expression patterns of five receptors (sst1-5 ). Among biological actions, the activation of central SST signaling induced a robust stimulation of food and water intake, which is mediated by the sst2 as assessed using selective sst agonists. The past years have witnessed the identification of brain SST circuitries involved using chemogenetic and optogenetic approaches and further established a physiological orexigenic role of brain SST signaling. The present review will discuss these recent findings.

OBJECTIVE Anorexia nervosa (AN) is an eating disorder characterized by body schema disruptions, underweight (>15% reduction of the ideal body weight or a body mass index

Nesfatin-1 was discovered in 2006 and introduced as a potential novel anorexigenic modulator of food intake and body weight. The past years have witnessed increasing evidence establishing nesfatin-1 as a potent physiological inhibitor of food intake and body weight and unravelled nesfatin-1's interaction with other brain transmitters to exert its food consumption inhibitory effect. As observed for other anorexigenic brain neuropeptides, nesfatin-1 is also likely to exert additional, if not pleiotropic, actions in the brain and periphery. Recent studies established the prominent expression of the nesfatin-1 precursor, nucleobindin2 (NUCB2), in the stomach and pancreas, where nesfatin-1 influences endocrine secretion. This review will highlight the current experimental state-of-knowledge on the effects of NUCB2/nesfatin-1 on food intake, body weight and glucose homeostasis. Potential implications in human obesity will be discussed in relation to the evidence of changes in circulating levels of NUCB2/nesfatin-1 in disease states, the occurrence of genetic NUCB2 polymorphisms and--in contrast to several other hormones--the independence of leptin signalling known to be blunted under conditions of chronically increased body weight.

Background Levodopa (l-dopa) is the most commonly used treatment for alleviating symptoms of Parkinson’s disease. However, l-dopa delays gastric emptying, which dampens its absorption. We investigated whether ghrelin prevents l-dopa action on gastric emptying and enhances circulating l-dopa in rats. Methods Gastric emptying of non-nutrient methylcellulose/phenol red viscous solution was determined in fasted rats treated with orogastric or intraperitoneal (i.p.) l-dopa, or intravenous (i.v.) ghrelin 10 min before orogastric l-dopa. Plasma l-dopa and dopamine levels were determined by high pressure liquid chromatography. Plasma acyl ghrelin levels were assessed by radioimmunoassay. Fos expression in the brain was immunostained after i.v. ghrelin (30 μg kg−1) 10 min before i.p. l-dopa. Key Results Levodopa (5 and 15 mg kg−1) decreased significantly gastric emptying by 32% and 62%, respectively, when administered orally, and by 91% and 83% when injected i.p. Ghrelin (30 or 100 μg kg−1, i.v.) completely prevented l-dopa’s (15 mg kg−1, orogastrically) inhibitory action on gastric emptying and enhanced plasma l-dopa and dopamine levels compared with vehicle 15 min after orogastric l-dopa. Levodopa (5 mg kg−1) did not modify plasma acyl ghrelin levels at 30 min, 1, and 2 h after i.v. injection. Levodopa (15 mg kg−1, i.p.) induced Fos in brain autonomic centers, which was not modified by i.v. ghrelin. Conclusions & Inferences Ghrelin counteracts l-dopa-induced delayed gastric emptying but not Fos induction in the brain and enhances circulating l-dopa levels. Potential therapeutic benefits of ghrelin agonists in Parkinson’s disease patients treated with l-dopa remain to be investigated.

Background Activation of brain somatostatin receptors (sst1–5) with the stable pan-sst1–5 somatostatin agonist, ODT8-SST blocks acute stress and central corticotropin-releasing factor (CRF)-mediated activation of endocrine and adrenal sympathetic responses. Brain CRF signaling is involved in delaying gastric emptying (GE) immediately post surgery. We investigated whether activation of brain sst signaling pathways modulates surgical stress-induced inhibition of gastric emptying and food intake. Methods Fasted rats were injected intracisternally (i.c.) with somatostatin agonists and underwent laparotomy and 1-min cecal palpation. Gastric emptying of a non-nutrient solution and circulating acyl and desacyl ghrelin levels were assessed 50 min post surgery. Food intake was monitored for 24 h. Key Results The abdominal surgery-induced inhibition of GE (65%), food intake (73% at 2 h) and plasma acyl ghrelin levels (67%) was completely prevented by ODT8-SST (1 μg per rat, i.c.). The selective sst5 agonist, BIM-23052 prevented surgery-induced delayed GE, whereas selective sst1, sst2, or sst4 agonists had no effect. However, the selective sst2 agonist, S-346-011 (1 μg per rat, i.c.) counteracted the abdominal surgery-induced inhibition of acyl ghrelin and food intake but not the delayed GE. The ghrelin receptor antagonist, [D-Lys3]-GHRP-6 (0.93 mg kg−1, intraperitoneal, i.p.) blocked i.p. ghrelin-induced increased GE, while not influencing i.c. ODT8-SST-induced prevention of delayed GE and reduced food intake after surgery. Conclusions & Inferences ODT8-SST acts in the brain to prevent surgery-induced delayed GE likely via activating sst5. ODT8-SST and the sst2 agonist prevent the abdominal surgery-induced decrease in food intake and plasma acyl ghrelin indicating dissociation between brain somatostatin signaling involved in preventing surgery-induced suppression of GE and feeding response.

Background Corticotropin-releasing factor (CRF) signaling induced by stress is well established to delay gastric emptying (GE) and stimulate colonic functions. The somatostatin receptor (sst1–5) agonist, ODT8-SST acts in the brain to inhibit stress-induced adrenocorticotropic hormone and epinephrine secretion. We investigated whether ODT8-SST acts in the brain to influence stress-related alterations of gastric and colonic motor function and sst receptor subtype(s) involved. Methods Peptides were injected intracerebroventricularly (i.c.v.) under short isoflurane anesthesia and GE, fecal pellet output (FPO) and distal colonic motility monitored in conscious mice. Key Results The stress of acute anesthesia/vehicle i.c.v. injection reduced GE by 67% and increased defecation by 99% compared to non-injected controls. Both responses were abolished by ODT8-SST (1 μg = 0.75 nmol) or sst1 agonist (0.65–1.95 nmol). The sst1 agonist (1.95 nmol) also prevented the abdominal surgery-induced delayed GE. Octreotide (sst2 > sst5 > sst3) and the sst2 or sst4 agonists (1 μg = 0.78 or 0.70 nmol, respectively) injected i.c.v. did not influence FPO while i.c.v. somatostatin-28 mimicked ODT8-SST’s effect. The ODT8-SST-induced increased food intake was inhibited by i.c.v. sst2 antagonist while the reduced FPO was unchanged. ODT8-SST i.c.v. reduced distal colonic motility in semi-restrained mice compared with vehicle and blocked water avoidance- and i.c.v. CRF (0.5 μg = 0.09 nmol)-induced stimulated FPO while a similar colonic secretomotor response to i.p. 5-hydroxytryptophane (10 mg kg−1 = 36.4 μmol kg−1) was unaltered. Conclusions & Inferences ODT8-SST counteracts stress/i.c.v. CRF-related stimulation of colonic motor function and delayed GE which can be reproduced mainly by activation of sst1 receptors. These data opens new insight to brain somatostatinergic signaling pathways interfering with brain circuitries involved in gut motor responses to acute stress.

The protein nucleobindin 2 (NUCB2) or NEFA (DNA binding/EF-hand/acidic amino acid rich region) was identified over a decade ago and implicated in intracellular processes. New developments came with the report that post-translational processing of hypothalamic NUCB2 may result in nesfatin-1, nesfatin-2 and nesfatin-3 and convergent studies showing that nesfatin-1 and full length NUCB2 injected in the brain potently inhibit the dark phase food intake in rodents including leptin receptor deficient Zucker rats. Nesfatin-1 also reduces body weight gain, suggesting a role as a new anorexigenic factor and modulator of energy balance. In light of the obesity epidemic and its associated diseases, underlying new mechanisms regulating food intake may be promising targets in the drug treatment of obese patients particularly as the vast majority of them display reduced leptin sensitivity or leptin resistance while nesfatin-1's mechanism of action is leptin independent. Although much progress on the localization of NUCB2/nesfatin-1 in the brain and periphery as well as on the understanding of nesfatin-1's anorexic effect have been achieved during the past three years, several important mechanisms have yet to be unraveled such as the identification of the nesfatin-1 receptor and the regulation of NUCB2 processing and nesfatin-1 release.