Breaking down barriers to bariatric care: a qualitative study on how telemedicine could transform patient experiences in a Swiss monocentric setting.

OBJECTIVE: Telemedicine is becoming an increasingly feasible option for patients with chronic diseases due to its convenience, cost-effectiveness and ease of access. While there are certain limitations, the benefits can be appreciated by those seeking repetitive care. The perception of telemedicine as an alternative to recurrent, in-person appointments for patients with obesity in structured bariatric programmes is still unclear. This content analysis' primary endpoint was to explore how patients within our bariatric programme perceived telemedicine and virtual consultations as a new way of communication during COVID-19. DESIGN: A qualitative study using semistructured interviews and qualitative content analysis method by Elo and Kyngäs following four steps: data familiarisation, coding and categorising with Quirkos software and final interpretation guided by developed categories. SETTING: University Hospital, Switzerland. PARTICIPANTS: We conducted 33 interviews with 19 patients from a structured bariatric programme. RESULTS: Most patients shared positive experiences, acknowledging the convenience and accessibility of virtual appointments. Others voiced concerns, especially regarding telemedicine's limitations. These reservations centred around the lack of physical examinations, difficulties in fostering connections with healthcare providers, as well as barriers stemming from language and technology. The research identified a spectrum of patient preferences in relation to telemedicine versus in-person visits, shaped by the immediacy of their concerns and their availability. CONCLUSION: While telemedicine is increasingly accepted by the public and provides accessible and cost-effective options for routine follow-up appointments, there are still obstacles to overcome, such as a lack of physical examination and technological limitations. However, integrating virtual alternatives, like phone or video consultations, into routine bariatric follow-ups could improve continuity and revolutionise bariatric care.

The Role of the Olfactory System in Obesity and Metabolism in Humans: A Systematic Review and Meta-Analysis.

Obesity, linked to chronic diseases, poses a global health challenge. While the role of the olfactory system in energy homeostasis is well-documented in rodents, its role in metabolism regulation and obesity in humans remains understudied. This review examines the interplay between olfactory function and metabolic alterations in human obesity and the effects of bariatric surgery on olfactory capabilities in humans. Adhering to PRISMA guidelines, a systematic review and meta-analysis was conducted, focusing exclusively on original human studies. From 51 articles, 14 were selected for the meta-analysis. It was found that variations in olfactory receptor genes influence the susceptibility to odors and predisposition to weight gain and poor eating habits. Bariatric surgery, particularly sleeve gastrectomy, shows significant improvements in olfactory function (SMD 2.37, 95% CI [0.96, 3.77], I = 92%, p = 0.001), especially regarding the olfactory threshold (SMD -1.65, 95% CI [-3.03, -0.27], I = 81%, p = 0.02). There is a bidirectional relationship between olfactory function and metabolism in humans. Bariatric surgery improves olfactory perception in obese patients, but it is still unclear if impacting the olfactory system directly affects eating behavior and the energy balance. However, these findings open novel avenues for future studies addressing the olfactory system as a novel target to alter systemic metabolism in humans.

The Impact of the COVID-19 Pandemic on Patients from a Bariatric Program: A Qualitative Analysis of Their Perceptions of Health and Well-Being.

INTRODUCTION: The study was conducted to explore the perceptions of patients from a bariatric program who have undergone or will undergo bariatric surgery during the ongoing COVID-19 pandemic, specifically as related to their struggles with health issues and their psychological well-being. MATERIALS AND METHODS: We conducted semi-structured, in-depth interviews with nineteen pre- or post-bariatric patients to generate data on their perceptions of COVID-19. Consistent with the methods of constructivist grounded theory, we collected and analyzed data iteratively through a constant comparative process for data coding and develop themes in the transcripts. RESULTS: We identified themes to summarize the pandemic-associated experiences of our cohort as follows: their life structure before COVID-19, the turning point with changes and adaptations, and the impact of isolation on psychological well-being. We identified grief due to loss of social contacts as well as physical and psychological health impairment as consequences of pandemic-related lifestyle changes. Most participants were not aware of overweight and obesity being major risk factors for worse outcomes of COVID-19. We developed a theme-based theory on patients' perceptions and fears regarding the pandemic as they live through phases of grief. DISCUSSION: Most participants shared critical perceptions about their own somatic and psychological health. These findings may inform recommendations and strategies for both patients and healthcare professionals to manage the challenges potentially presented by this vulnerable patient group in the context of the COVID-19 pandemic.

Regular intake of energy drinks and multivitamin supplements is associated with elevated plasma vitamin B6 levels in post-bariatric patients.

The aim of the present survey was to analyze plasma vitamin B6 levels in post-bariatric patients and to elucidate the causal factors associated with elevated plasma vitamin B6 levels. This is a retrospective analysis of electronic patient data of all post-bariatric patients evaluated at the endocrine outpatient clinic of the University Hospital Basel in 2017, for which plasma vitamin B6 values were assessed during regular follow-up visits. In total, 205 patients were included in the study, whereof a minority of 43% had vitamin B6 levels in the normal range. 50% of the patients had vitamin B6 levels up to fourfold higher than the upper normal limit and 7% had levels more than fourfold above the upper normal limit. Vitamin B6 deficiency was not observed in any patient. While multivitamin supplementation in general was associated with elevated plasma vitamin B6 levels, the highest vitamin B6 levels were found after biliopancreatic diversion (BPD) and in patients who reported daily energy drink intake. Elevated plasma vitamin B6 levels up to fourfold above the upper normal limit are common in postbariatric patients and are associated with regular multivitamin supplementation, while highly elevated plasma vitamin B6 levels were seen primarily upon regular energy drink intake. Thus, a regular follow-up of vitamin B6 plasma levels and critical evaluation of vitamin B6 supplementation, either as part of the multivitamin preparation or related to regular energy drink intake, is highly warranted and should be an integral part of the routine post-bariatric follow-up.

GLP-1 secretion is regulated by IL-6 signalling: a randomised, placebo-controlled study.

AIMS/HYPOTHESIS: IL-6 is a cytokine with various effects on metabolism. In mice, IL-6 improved beta cell function and glucose homeostasis via upregulation of glucagon-like peptide 1 (GLP-1), and IL-6 release from muscle during exercise potentiated this beneficial increase in GLP-1. This study aimed to identify whether exercise-induced IL-6 has a similar effect in humans. METHODS: In a multicentre, double-blind clinical trial, we randomly assigned patients with type 2 diabetes or obesity to intravenous tocilizumab (an IL-6 receptor antagonist) 8 mg/kg every 4 weeks, oral sitagliptin (a dipeptidyl peptidase-4 inhibitor) 100 mg daily or double placebos (a placebo saline infusion every 4 weeks and a placebo pill once daily) during a 12 week training intervention. The primary endpoints were the difference in change of active GLP-1 response to an acute exercise bout and change in the AUC for the concentration-time curve of active GLP-1 during mixed meal tolerance tests at baseline and after the training intervention. RESULTS: Nineteen patients were allocated to tocilizumab, 17 to sitagliptin and 16 to placebos. During the acute exercise bout active GLP-1 levels were 26% lower with tocilizumab (multiplicative effect: 0.74 [95% CI 0.56, 0.98], p = 0.034) and 53% higher with sitagliptin (1.53 [1.15, 2.03], p = 0.004) compared with placebo. After the 12 week training intervention, the active GLP-1 AUC with sitagliptin was about twofold that with placebo (2.03 [1.56, 2.62]; p < 0.001), while GLP-1 AUC values showed a small non-significant decrease of 13% at 4 weeks after the last tocilizumab infusion (0.87 [0.67, 1.12]; p = 0.261). CONCLUSIONS/INTERPRETATION: IL-6 is implicated in the regulation of GLP-1 in humans. IL-6 receptor blockade lowered active GLP-1 levels in response to a meal and an acute exercise bout in a reversible manner, without lasting effects beyond IL-6 receptor blockade. TRIAL REGISTRATION: Clinicaltrials.gov NCT01073826. FUNDING: Danish National Research Foundation. Danish Council for Independent Research. Novo Nordisk Foundation. Danish Centre for Strategic Research in Type 2 Diabetes. European Foundation for the Study of Diabetes. Swiss National Research Foundation.

IL-6/Stat3-Dependent Induction of a Distinct, Obesity-Associated NK Cell Subpopulation Deteriorates Energy and Glucose Homeostasis.

Natural killer (NK) cells contribute to the development of obesity-associated insulin resistance. We demonstrate that in mice obesity promotes expansion of a distinct, interleukin-6 receptor (IL6R)a-expressing NK subpopulation, which also expresses a number of other myeloid lineage genes such as the colony-stimulating factor 1 receptor (Csf1r). Selective ablation of this Csf1r-expressing NK cell population prevents obesity and insulin resistance. Moreover, conditional inactivation of IL6Ra or Stat3 in NK cells limits obesity-associated formation of these myeloid signature NK cells, protecting from obesity, insulin resistance, and obesity-associated inflammation. Also in humans IL6Ra+ NK cells increase in obesity and correlate with markers of systemic low-grade inflammation, and their gene expression profile overlaps with characteristic gene sets of NK cells in obese mice. Collectively, we demonstrate that obesity-associated inflammation and metabolic disturbances depend on interleukin-6/Stat3-dependent formation of a distinct NK population, which may provide a target for the treatment of obesity, metaflammation-associated pathologies, and diabetes.

IL-6 Improves Energy and Glucose Homeostasis in Obesity via Enhanced Central IL-6 trans-Signaling.

Interleukin (IL)-6 engages similar signaling mechanisms to leptin. Here, we find that central application of IL-6 in mice suppresses feeding and improves glucose tolerance. In contrast to leptin, whose action is attenuated in obesity, the ability of IL-6 to suppress feeding is enhanced in obese mice. IL-6 suppresses feeding in the absence of neuronal IL-6-receptor (IL-6R) expression in hypothalamic or all forebrain neurons of mice. Conversely, obese mice exhibit increased soluble IL-6R levels in the cerebrospinal fluid. Blocking IL-6 trans-signaling in the CNS abrogates the ability of IL-6 to suppress feeding. Furthermore, gp130 expression is enhanced in the paraventricular nucleus of the hypothalamus (PVH) of obese mice, and deletion of gp130 in the PVH attenuates the beneficial central IL-6 effects on metabolism. Collectively, these experiments indicate that IL-6 trans-signaling is enhanced in the CNS of obese mice, allowing IL-6 to exert its beneficial metabolic effects even under conditions of leptin resistance.

Inhibition of P2Y6 Signaling in AgRP Neurons Reduces Food Intake and Improves Systemic Insulin Sensitivity in Obesity.

Uridine-diphosphate (UDP) and its receptor P2Y6 have recently been identified as regulators of AgRP neurons. UDP promotes feeding via activation of P2Y6 receptors on AgRP neurons, and hypothalamic UDP concentrations are increased in obesity. However, it remained unresolved whether inhibition of P2Y6 signaling pharmacologically, globally, or restricted to AgRP neurons can improve obesity-associated metabolic dysfunctions. Here, we demonstrate that central injection of UDP acutely promotes feeding in diet-induced obese mice and that acute pharmacological blocking of CNS P2Y6 receptors reduces food intake. Importantly, mice with AgRP-neuron-restricted inactivation of P2Y6 exhibit reduced food intake and fat mass as well as improved systemic insulin sensitivity with improved insulin action in liver. Our results reveal that P2Y6 signaling in AgRP neurons is involved in the onset of obesity-associated hyperphagia and systemic insulin resistance. Collectively, these experiments define P2Y6 as a potential target to pharmacologically restrict both feeding and systemic insulin resistance in obesity.

Postprandial macrophage-derived IL-1ß stimulates insulin, and both synergistically promote glucose disposal and inflammation.

The deleterious effect of chronic activation of the IL-1ß system on type 2 diabetes and other metabolic diseases is well documented. However, a possible physiological role for IL-1ß in glucose metabolism has remained unexplored. Here we found that feeding induced a physiological increase in the number of peritoneal macrophages that secreted IL-1ß, in a glucose-dependent manner. Subsequently, IL-1ß contributed to the postprandial stimulation of insulin secretion. Accordingly, lack of endogenous IL-1ß signaling in mice during refeeding and obesity diminished the concentration of insulin in plasma. IL-1ß and insulin increased the uptake of glucose into macrophages, and insulin reinforced a pro-inflammatory pattern via the insulin receptor, glucose metabolism, production of reactive oxygen species, and secretion of IL-1ß mediated by the NLRP3 inflammasome. Postprandial inflammation might be limited by normalization of glycemia, since it was prevented by inhibition of the sodium-glucose cotransporter SGLT2. Our findings identify a physiological role for IL-1ß and insulin in the regulation of both metabolism and immunity.

Glucose-Dependent Insulinotropic Peptide Stimulates Glucagon-Like Peptide 1 Production by Pancreatic Islets via Interleukin 6, Produced by α Cells.

BACKGROUND & AIMS: Glucose-dependent insulinotropic peptide (GIP) induces production of interleukin 6 (IL6) by adipocytes. IL6 increases production of glucagon-like peptide (GLP)-1 by L cells and α cells, leading to secretion of insulin from ß cells. We investigated whether GIP regulates GLP1 and glycemia via IL6. METHODS: We obtained samples of human pancreatic islets and isolated islets from mice; human α cells and ß cells were sorted by flow cytometry and incubated with GIP. Islets were analyzed by quantitative polymerase chain reaction and immunohistochemistry. BKS.Cg-Dock7m+/+ Leprdb/J db/db mice (diabetic mice) and db/+ mice, as well as C57BL/6J IL6-knockout mice (IL6-KO) and C57BL/6J mice with the full-length Il6 gene (controls), were fed a chow or a high-fat diet; some mice were given injections of recombinant GIP, IL6, GLP, a neutralizing antibody against IL6 (anti-IL6), lipopolysaccharide, and/or IL1B. Mice were given a glucose challenge and blood samples were collected and analyzed. RESULTS: Incubation of mouse and human pancreatic α cells with GIP induced their production of IL6, leading to production of GLP1 and insulin secretion from pancreatic islets. This did not occur in islets from IL6-KO mice or in islets incubated with anti-IL6. Incubation of islets with IL1B resulted in IL6 production but directly reduced GLP1 production. Incubation of mouse islets with the sodium glucose transporter 2 inhibitor dapagliflozin induced production of GLP1 and IL6. Injection of control mice with GIP increased plasma levels of GLP1, insulin, and glucose tolerance; these effects were amplified in mice given lipopolysaccharide but reduced in IL6-KO mice or in mice given anti-IL6. Islets from diabetic mice had increased levels of IL1B and IL6, compared with db/+ mice, but injection of GIP did not lead to production of GLP1 or reduce glycemia. CONCLUSIONS: In studies of pancreatic islets from human beings and mice, we found that GIP induces production of IL6 by α cells, leading to islet production of GLP1 and insulin. This process is regulated by inflammation, via IL1B, and by sodium glucose transporter 2. In diabetic mice, increased islet levels of IL6 and IL1B might increase or reduce the production of GLP1 and affect glycemia.

Muscle-Derived IL-6 Is Not Regulated by IL-1 during Exercise. A Double Blind, Placebo-Controlled, Randomized Crossover Study.

UNLABELLED: Exercise increases muscle derived Interleukin­6 (IL­6) leading to insulin secretion via glucagon-like peptide­1. IL­1 antagonism improves glycemia and decreases systemic inflammation including IL­6 in patients with type 2 diabetes. However, it is not known whether physiological, exercise-induced muscle-derived IL­6 is also regulated by the IL­1 system. Therefore we conducted a double blind, crossover study in 17 healthy male subjects randomized to receive either the IL­1 receptor antagonist IL-1Ra (anakinra) or placebo prior to an acute treadmill exercise. Muscle activity led to a 2­3 fold increase in serum IL­6 concentrations but anakinra had no effect on this exercise-induced IL­6. Furthermore, the IL­1 responsive inflammatory markers CRP, cortisol and MCP­1 remained largely unaffected by exercise and anakinra. We conclude that the beneficial effect of muscle-induced IL­6 is not meaningfully affected by IL­1 antagonism. TRIAL REGISTRATION: ClinicalTrials.gov NCT01771445.

Interleukin-6 contributes to early fasting-induced free fatty acid mobilization in mice.

Contracting muscle releases interleukin-6 (IL-6) enabling the metabolic switch from carbohydrate to fat utilization. Similarly, metabolism is switched during transition from fed to fasting state. Herein, we examined a putative role for IL-6 in the metabolic adaptation to normal fasting. In lean C57BL/6J mice, 6 h of food withdrawal increased gene transcription levels of IL-6 in skeletal muscle but not in white adipose tissue. Concomitantly, circulating IL-6 and free fatty acid (FFA) levels were significantly increased, whereas respiratory quotient (RQ) was reduced in 6-h fasted mice. In white adipose tissue, phosphorylation of hormone-sensitive lipase (HSL) was increased on fasting, indicating increased lipolysis. Intriguingly, fasting-induced increase in circulating IL-6 levels and parallel rise in FFA concentration were absent in obese and glucose-intolerant mice. A causative role for IL-6 in the physiological adaptation to fasting was further supported by the fact that fasting-induced increase in circulating FFA levels was significantly blunted in lean IL-6 knockout (KO) and lean C57BL/6J mice treated with neutralizing IL-6 antibody. Consistently, phosphorylation of HSL was significantly reduced in adipose tissue of IL-6-depleted mice. Hence, our findings suggest a novel role for IL-6 in energy supply during early fasting.

Glucose-dependent insulinotropic polypeptide induces cytokine expression, lipolysis, and insulin resistance in human adipocytes.

Obesity-related insulin resistance is linked to a chronic state of systemic and adipose tissue-derived inflammation. Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone also acting on adipocytes. We investigated whether GIP affects inflammation, lipolysis, and insulin resistance in human adipocytes. Human subcutaneous preadipocyte-derived adipocytes, differentiated in vitro, were treated with human GIP to analyze mRNA expression and protein secretion of cytokines, glycerol, and free fatty acid release and insulin-induced glucose uptake. GIP induced mRNA expression of IL-6, IL-1ß, and the IL-1 receptor antagonist IL-1Ra, whereas TNFα, IL-8, and monocyte chemotactic protein (MCP)-1 remained unchanged. Cytokine induction involved PKA and the NF-κB pathway as well as an autocrine IL-1 effect. Furthermore, GIP potentiated IL-6 and IL-1Ra secretion in the presence of LPS, IL-1ß, and TNFα. GIP induced lipolysis via activation of hormone-sensitive lipase and was linked to NF-κB activation. Finally, chronic GIP treatment impaired insulin-induced glucose uptake possibly due to the observed impaired translocation of glucose transporter GLUT4. In conclusion, GIP induces an inflammatory and prolipolytic response via the PKA -NF-κB-IL-1 pathway and impairs insulin sensitivity of glucose uptake in human adipocytes.

Diabetes mellitus Type 2--the new face of an old lady.

Already 600 years before Christ, type 2 diabetes was known as a disease of elevated blood sugar levels associated with obesity. Since then, it appears, our understanding of the disease has not changed much, aside from the replacement of tasting the patients' urine by the measurement of plasma glucose and glycated haemoglobin levels (HbA1c) for its diagnosis and the discovery of some new drugs. Already, in those old days a physician from India named Sushrut described diabetes mellitus as a disease characterised by the passage of large amounts of urine and its "honey-like" taste and, noteworthy, as a disease that is mainly associated with obesity and a sedentary lifestyle, recommending physical activity as the primary treatment option. Although these milestone observations remain valid, major progress in the underlying pathogenesis of type 2 diabetes has been achieved showing a new face of this old disease and opening doors for novel treatment options. This review will highlight recent pathophysiological aspects of type 2 diabetes, actual diagnostic and treatment guidelines and discuss some possible upcoming new therapeutic strategies.

Both inflammatory and classical lipolytic pathways are involved in lipopolysaccharide-induced lipolysis in human adipocytes.

High fat diet-induced endotoxaemia triggers low-grade inflammation and lipid release from adipose tissue. This study aims to unravel the cellular mechanisms leading to the lipopolysaccharide (LPS) effects in human adipocytes. Subcutaneous pre-adipocytes surgically isolated from patients were differentiated into mature adipocytes in vitro. Lipolysis was assessed by measurement of glycerol release and mRNA expression of pro-inflammatory cytokines were evaluated by real-time PCR. Treatment with LPS for 24 h induced a dose-dependent increase in interleukin (IL)-6 and IL-8 mRNA expression. At 1 µg/ml LPS, IL-6 and IL-8 were induced to 19.5 ± 1.8-fold and 662.7 ± 91.5-fold (P < 0.01 vs basal), respectively. From 100 ng/ml to 1 µg/ml, LPS-induced lipolysis increased to a plateau of 3.1-fold above basal level (P < 0.001 vs basal). Co-treatment with inhibitors of inhibitory kappa B kinase kinase beta (IKKß) or NF-κB inhibited LPS-induced glycerol release. Co-treatment with the protein kinase A (PKA) inhibitor H-89, the lipase inhibitor orlistat or the hormone-sensitive lipase (HSL) inhibitor CAY10499 abolished the lipolytic effects of LPS. Co-treatment with the MAPK inhibitor, U0126 also reduced LPS-induced glycerol release. Inhibition of lipolysis by orlistat or CAY10499 reduced LPS-induced IL-6 and IL-8 mRNA expression. Induction of lipolysis by the synthetic catecholamine isoproterenol or the phosphodiesterase type III inhibitor milrinone did not alter basal IL-6 and IL-8 mRNA expression after 24 treatments whereas these compounds enhanced LPS-induced IL-6 and IL-8 mRNA expression. Both the inflammatory IKKß/NF-κB pathway and the lipolytic PKA/HSL pathways mediate LPS-induced lipolysis. In turn, LPS-induced lipolysis reinforces the expression of pro-inflammatory cytokines and, thereby, triggers its own lipolytic activity.

Metformin counters both lipolytic/inflammatory agents-decreased hormone sensitive lipase phosphorylation at Ser-554 and -induced lipolysis in human adipocytes.

OBJECTIVE: To study the effects of metformin on lipolysis and hormone sensitive lipase (HSL) phosphorylation in human adipocytes treated with lipolytic and inflammatory agents. METHODS: Lipolysis and phosphorylation status of HSL were assessed in subcutaneous pre-adipocytes surgically isolated from patients and differentiated into mature adipocytes in vitro. RESULTS: Stimulation for 1 h with forskolin, isoproterenol and IBMX or stimulation for 24 h with LPS, IL-1ß and TNF-α increased lipolysis (p < 0.05 vs. basal). The phosphorylation of HSL at Ser-554 was decreased while the Ser-552 phosphorylation was increased. Pre-incubation with metformin (24 h, 1 mM) inhibited forskolin-, isoproterenol-, IBMX-, LPS-, IL-1ß- and TNF-α-induced glycerol release and prevented p(Ser554)HSL decrease and p(Ser-552)HSL increase due to lipolytic and inflammatory agents. AMPKα1 is involved in metformin-induced HSL phosphorylation at Ser-552. CONCLUSION: Phosphorylation of HSL at Ser-554 inversely correlates with lipolysis and HSL phosphorylation at Ser552 in human adipocytes.

Glucose-dependent insulinotropic polypeptide (GIP) induces calcitonin gene-related peptide (CGRP)-I and procalcitonin (Pro-CT) production in human adipocytes.

CONTEXT: Increased plasma levels of glucose-dependent insulinotropic polypeptide (GIP), calcitonin CT gene-related peptide (CGRP)-I, and procalcitonin (Pro-CT) are associated with obesity. Adipocytes express functional GIP receptors and the CT peptides Pro-CT and CGRP-I. However, a link between GIP and CT peptides has not been studied yet. OBJECTIVE: The objective of the study was the assessment of the GIP effect on the expression and secretion of CGRP-I and Pro-CT in human adipocytes, CGRP-I and CT gene expression in adipose tissue (AT) from obese vs. lean subjects, and plasma levels of CGRP-I and Pro-CT after a high-fat meal in obese patients. DESIGN AND PARTICIPANTS: Human preadipocyte-derived adipocytes, differentiated in vitro, were treated with GIP. mRNA expression and protein secretion of CGRP-I and Pro-CT were measured. Human CGRP-I and CT mRNA expression in AT and CGRP-I and Pro-CT plasma concentrations were assessed. RESULTS: Treatment with 1 nm GIP induced CGRP-I mRNA expression 6.9 ± 1.0-fold (P < 0.001 vs. control) after 2 h and CT gene expression 14.0 ± 1.7-fold (P < 0.001 vs. control) after 6 h. GIP stimulated CGRP-I secretion 1.7 ± 0.2-fold (P < 0.05 vs. control) after 1 h. In AT samples of obese subjects, CGRP-I mRNA expression was higher in sc AT (P < 0.05 vs. lean subjects), whereas CT expression was higher in visceral AT (P < 0.05 vs. lean subjects). CGRP-I plasma levels increased after a high-fat meal in obese patients. CONCLUSION: GIP induces CGRP-I and CT expression in human adipocytes. Therefore, elevated Pro-CT and CGRP-I levels in obesity might result from GIP-induced Pro-CT and CGRP-I release in AT and might be triggered by a high-fat diet. How these findings relate to the metabolic complications of obesity warrants further investigations.

Human adipose tissue-derived mesenchymal stem cells differentiate into insulin, somatostatin, and glucagon expressing cells.

Mesenchymal stem cells (MSC) from mouse bone marrow were shown to adopt a pancreatic endocrine phenotype in vitro and to reverse diabetes in an animal model. MSC from human bone marrow and adipose tissue represent very similar cell populations with comparable phenotypes. Adipose tissue is abundant and easily accessible and could thus also harbor cells with the potential to differentiate in insulin producing cells. We isolated human adipose tissue-derived MSC from four healthy donors. During the proliferation period, the cells expressed the stem cell markers nestin, ABCG2, SCF, Thy-1 as well as the pancreatic endocrine transcription factor Isl-1. The cells were induced to differentiate into a pancreatic endocrine phenotype by defined culture conditions within 3 days. Using quantitative PCR a down-regulation of ABCG2 and up-regulation of pancreatic developmental transcription factors Isl-1, Ipf-1, and Ngn3 were observed together with induction of the islet hormones insulin, glucagon, and somatostatin.