Obesity changes the human gut mycobiome

The human intestine is home to a diverse range of bacterial and fungal species, forming an ecological community that contributes to normal physiology and disease susceptibility. Here, the fungal microbiota (mycobiome) in obese and non-obese subjects was characterized using Internal Transcribed Spacer (ITS)-based sequencing. The results demonstrate that obese patients could be discriminated by their specific fungal composition, which also distinguished metabolically “healthy” from “unhealthy” obesity. Clusters according to genus abundance co-segregated with body fatness, fasting triglycerides and HDL-cholesterol. A preliminary link to metabolites such as hexadecanedioic acid, caproic acid and N-acetyl-L-glutamic acid was also found. Mucor racemosus and M. fuscus were the species more represented in non-obese subjects compared to obese counterparts. Interestingly, the decreased relative abundance of the Mucor genus in obese subjects was reversible upon weight loss. Collectively, these findings suggest that manipulation of gut mycobiome communities might be a novel target in the treatment of obesity

Molecular characterization of epithelial-mesenchymal transition and medical treatment related-genes in non-functioning pituitary neuroendocrine tumors

Different medical therapies have been developed for pituitary adenomas. However, Non-Functioning Pituitary Neuroendocrine Tumors (NF-PitNET) have shown little response to them. Furthermore, epithelial-mesenchymal transition (EMT) has been linked to resistance to medical treatment in a significant number of tumors, including pituitary adenomas. We aimed to evaluate the expression of EMT-related markers in 72 NF-PitNET and 16 non-tumoral pituitaries. To further explore the potential usefulness of medical treatment for NF-PitNET we assessed the expression of somatostatin receptors and dopamine-associated genes. We found that SNAI1, SNAI2, Vimentin, KLK10, PEBP1, Ki-67 and SSTR2 were associated with invasive NF-PitNET. Furthermore, we found that the EMT phenomenon was more common in NF-PitNET than in GH-secreting pituitary tumors. Interestingly, PEBP1 was overexpressed in recurrent NF-PitNET, and could predict growth recurrence with 100% sensitivity but only 43% specificity. In parallel with previously reported studies, SSTR3 is highly expressed in our NF-PitNET cohort. However, SSTR3 expression is highly heterogeneous among the different histological variants of NF-PitNET with very low levels in silent corticotroph adenomas. NF-PitNET showed an enhanced EMT phenomenon. SSTR3 targeting could be a good therapeutic candidate in NF-PitNET except for silent corticotroph adenomas, which express very low levels of this receptor. In addition, PEBP1 could be an informative biomarker of tumor regrowth, useful for predictive medicine in NF-PitNET

Iron and obesity status-associated insulin resistance influence circulating fibroblast-growth factor-23 concentrations

Fibroblast growth factor 23 (FGF-23) is known to be produced by the bone and linked to metabolic risk. We aimed to explore circulating FGF-23 in association with fatness and insulin sensitivity, atherosclerosis and bone mineral density (BMD). Circulating intact FGF-23 (iFGF-23) and C-terminal (CtFGF-23) concentrations (ELISA) were measured in 133 middle aged men from the general population in association with insulin sensitivity (Cohort 1); and in association with fat mass and bone mineral density (DEXA) and atherosclerosis (intima media thickness, IMT) in 78 subjects (52 women) with a wide range of adiposity (Cohort 2). Circulating iFGF-23 was also measured before and after weight loss. In all subjects as a whole, serum intact and C-terminal concentrations were linearly and positively associated with BMI. In cohort 1, both serum iFGF-23 and CtFGF-23 concentrations increased with insulin resistance. Serum creatinine contributed to iFGF-23 variance, while serum ferritin and insulin sensitivity (but not BMI, age or serum creatinine) contributed to 17% of CtFGF-23 variance. In cohort 2, CtFGF-23 levels were higher in women vs. men, and increased with BMI, fat mass, fasting and post-load serum glucose, insulin, HOMA-IR and PTH, being negatively associated with circulating vitamin D and ferritin levels. The associations of CtFGF-23 with bone density in the radius, lumbar spine and carotid IMT were no longer significant after controlling for BMI. Weight loss led to decreased iFGF-23 concentrations. In summary, the associations of circulating FGF-23 concentration with parameters of glucose metabolism, bone density and atherosclerosis are dependent on iron and obesity status-associated insulin resistance

Revisiting the usefulness of the short acute octreotide test to predict treatment outcomes in acromegaly

Introduction: We previously described that a short version of the acute octreotide test (sAOT) can predict the response to first-generation somatostatin receptor ligands (SRLs) in patients with acromegaly. We have prospectively reassessed the sAOT in patients from the ACROFAST study using current ultra-sensitive GH assays. We also studied the correlation of sAOT with tumor expression of E-cadherin and somatostatin receptor 2 (SSTR2) .Methods: A total of 47 patients treated with SRLs for 6 months were evaluated with the sAOT at diagnosis and correlated with SRLs' response. Those patients whose IGF1 decreased to = 3SDS, were considered non-responders. The 2 hours GH value (GH2h) after s.c. administration of 100 mcg of octreotide was used to define predictive cutoffs. E-cadherin and SSTR2 immunostaining in somatotropinoma tissue were investigated in 24/47 and 18/47 patients, respectively.Results: In all, 30 patients were responders and 17 were non-responders. GH(2h) was 0.68 (0.25-1.98) ng/mL in responders vs 2.35 (1.59-9.37) ng/mL in non-responders (p<0.001). GH(2h) = 1.4ng/mL showed the highest ability to identify responders (accuracy of 81%, sensitivity of 73.3%, and specificity of 94.1%). GH(2h) = 4.3ng/mL was the best cutoff for non-response prediction (accuracy of 74%, sensitivity of 35.3%, and specificity of 96.7%). Patients with E-cadherin-positive tumors showed a lower GH(2h) than those with E-cadherin-negative tumors [0.9 (0.3-2.1) vs 3.3 (1.5-12.1) ng/mL; p<0.01], and patients with positive E-cadherin presented a higher score of SSTR2 (7.5 +/- 4.2 vs 3.3 +/- 2.1; p=0.01).Conclusion: The sAOT is a good predictor tool for assessing response to SRLs and correlates with tumor E-cadherin and SSTR2 expression. Thus, it can be useful in clinical practice for therapeutic decision-making in patients with acromegaly

Revisiting the usefulness of the short acute octreotide test to predict treatment outcomes in acromegaly

IntroductionWe previously described that a short version of the acute octreotide test (sAOT) can predict the response to first-generation somatostatin receptor ligands (SRLs) in patients with acromegaly. We have prospectively reassessed the sAOT in patients from the ACROFAST study using current ultra-sensitive GH assays. We also studied the correlation of sAOT with tumor expression of E-cadherin and somatostatin receptor 2 (SSTR2) .MethodsA total of 47 patients treated with SRLs for 6 months were evaluated with the sAOT at diagnosis and correlated with SRLs’ response. Those patients whose IGF1 decreased to &lt;3SDS from normal value were considered responders and those whose IGF1 was ≥3SDS, were considered non-responders. The 2 hours GH value (GH2h) after s.c. administration of 100 mcg of octreotide was used to define predictive cutoffs. E-cadherin and SSTR2 immunostaining in somatotropinoma tissue were investigated in 24/47 and 18/47 patients, respectively.ResultsIn all, 30 patients were responders and 17 were non-responders. GH2h was 0.68 (0.25-1.98) ng/mL in responders vs 2.35 (1.59-9.37) ng/mL in non-responders (p&lt;0.001). GH2h = 1.4ng/mL showed the highest ability to identify responders (accuracy of 81%, sensitivity of 73.3%, and specificity of 94.1%). GH2h = 4.3ng/mL was the best cutoff for non-response prediction (accuracy of 74%, sensitivity of 35.3%, and specificity of 96.7%). Patients with E-cadherin-positive tumors showed a lower GH2h than those with E-cadherin-negative tumors [0.9 (0.3-2.1) vs 3.3 (1.5-12.1) ng/mL; p&lt;0.01], and patients with positive E-cadherin presented a higher score of SSTR2 (7.5 ± 4.2 vs 3.3 ± 2.1; p=0.01).ConclusionThe sAOT is a good predictor tool for assessing response to SRLs and correlates with tumor E-cadherin and SSTR2 expression. Thus, it can be useful in clinical practice for therapeutic decision-making in patients with acromegaly

Estudi dels canvis promoguts per la cirurgia bariàtrica a nivell d'expressió gènica del teixit adipós subcutani i la relació amb la sensibilitat a la insulina

INTRODUCTION: Bariatric surgery (CB) is the only treatment option that has proved capable of solving the DM2. In addition to the impact on weight and comorbidities, the CB has shown a great impact on adipose tissue. THEORY: The CB modifies gene expression of subcutaneous adipose tissue (SAT) and helps explain changes in insulin sensitivity. OBJECTIVES: To evaluate changes in gene expression SAT after weight loss promoted by the CB and the association with clinical variables that change after the CB. SUBJECTS AND METHODS: To evaluate changes in gene expression SAT promoted by the CB, a cohort study comprised 25 women morbidly obese, bariatric surgery operated by gastric bypass (Cohort 1). The associations found are explored in a cohort of 25 women matched by age (Cohort 2) and in a cohort of patients (n = 132) men and women, obese and non-obese (Cohort 3). RESULTS: Statistically significant changes observed in the expression of 5,018 transcripts explored the 49,852 level SAT. A decrease in the expression of genes related to pro-inflammatory and iron metabolism and an increase in the expression of genes involved in lipogènics and insulin sensitivity. CONCLUSIONS: Weight loss promoted by CB drastically modifies gene expression in SAT, inducing the transition to a less dysfunctional adipose tissue and metabolically favorableINTRODUCCIÓ: La cirurgia de la obesitat (cirurgia bariàtrica, CB) és la única opció de tractament que ha demostrat ser capaç de resoldre la DM2. A més de l’impacte en el pes i les comorbilitats, la CB ha demostrat tenir un gran impacte en el teixit adipós. HIPÒTESI: La CB modifica l’expressió gènica del teixit adipós subcutani (SAT) i contribueix a explicar els canvis en la sensibilitat a la insulina. OBJECTIUS: Avaluar els canvis en l’expressió gènica de SAT després de la pèrdua de pes promoguda per la CB i l’associació amb les variables clíniques que més modifiquen després de la CB. SUBJECTES I METODOLOGIA: Per valorar els canvis en l’expressió gènica de SAT promoguts per la CB, s’estudia una cohort conformada per 25 dones obeses mòrbides, operades de cirurgia bariàtrica mitjançant bypass gàstric (Cohort 1). Les associacions trobades són explorades en unacohort conformada per 25 dones primes aparellades per edat (Cohort 2) i en una cohort ampliada de pacients (n=132) homes i dones, obesos i no obesos (Cohort 3). RESULTATS: S’observa canvis estadísticament significatius en l’expressió de 5.018 dels 49.852 trànscrits explorats a nivell de SAT. S’observa una disminució de l’expressió de gens pro-inflamatoris i relacionats amb el metabolisme del ferro i un increment en l’expressió de gens lipogènics i implicats en la sensibilitat a la insulina. CONCLUSIONS: La pèrdua de pes promoguda per la CB modifica dràsticament l’expressió gènica en SAT, induint el pas a un teixit adipós menys disfuncional i metabòlicament més favorabl