Publications by authors named "Felipe Casanueva"

324 Publications

Adipose tissue and blood leukocytes ACE2 DNA methylation in obesity and after weight loss.

Eur J Clin Invest 2021 Sep 28:e13685. Epub 2021 Sep 28.

Epigenomics in Endocrinology and Nutrition Group, Epigenomics Unit, Instituto de Investigacion Sanitaria de Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago de Compostela (CHUS/SERGAS), Santiago de Compostela, Spain.

Background: Obesity was consistently associated with a poor prognosis in patients with COVID-19. Epigenetic mechanisms were proposed as the link between obesity and comorbidities risk.

Aim: To evaluate the methylation levels of angiotensin-converting enzyme 2 (ACE2) gene, the main entry receptor of SARS-CoV-2, in different depots of adipose tissue (AT) and leukocytes (PBMCs) in obesity and after weight loss therapy based on a very-low-calorie ketogenic diet (VLCKD), a balanced hypocaloric diet (HCD) or bariatric surgery (BS).

Materials And Methods: DNA methylation levels of ACE2 were extracted from our data sets generated by the hybridization of subcutaneous (SAT) (n = 32) or visceral (VAT; n = 32) adipose tissue, and PBMCs (n = 34) samples in Infinium HumanMethylation450 BeadChips. Data were compared based on the degree of obesity and after 4-6 months of weight loss either by following a nutritional or surgical treatment and correlated with ACE2 transcript levels.

Results: As compared with normal weight, VAT from patients with obesity showed higher ACE2 methylation levels. These differences were mirrored in PBMCs but not in SAT. The observed obesity-associated methylation of ACE2 was reversed after VLCKD and HCD but not after BS. Among the studied CpG sites, cg16734967 and cg21598868, located at the promoter, were the most affected and correlated with BMI. The observed DNA methylation pattern was inversely correlated with ACE2 expression.

Conclusion: Obesity-related VAT shows hypermethylation and downregulation of the ACE2 gene that is mirrored in PBMCs and is restored after nutritional weight reduction therapy. The results warrant the necessity to further evaluate its implication for COVID-19 pathogenesis.
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http://dx.doi.org/10.1111/eci.13685DOI Listing
September 2021

Inflammatory markers are associated with quality of life, physical activity, and gait speed but not sarcopenia in aged men (40-79 years).

J Cachexia Sarcopenia Muscle 2021 Sep 15. Epub 2021 Sep 15.

Geriatrics and Gerontology, Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium.

Background: Age-related chronic low-grade inflammation (inflammaging) is one of the proposed mechanisms behind sarcopenia. However, findings regarding inflammatory markers in sarcopenic older adults are conflicting. This study aimed to determine the association between inflammatory markers, prevalent as well as incident sarcopenia, sarcopenia-defining parameters, quality of life (QoL), and physical activity in middle-aged and older men.

Methods: Men aged 40-79 years (mean 59.66 ± 11.00y) were recruited from population registers in eight European centres for participation in the European Male Aging study (EMAS). Subjects were assessed at baseline (2003-2005) and again after a median follow-up of 4.29 years. In 2577 participants, associations between baseline inflammatory markers [high-sensitive C-reactive protein (hs-CRP), white blood cell count (WBC), albumin] and baseline physical activity (PASE) and QoL (SF-36) were analysed. In the Leuven and Manchester cohort (n = 447), data were available on muscle mass (whole-body dual X-ray absorptiometry) and strength. In this subgroup, cross-sectional associations between baseline inflammatory markers and sarcopenia-defining parameters (handgrip strength, chair stand test, appendicular lean mass, and gait speed) and prevalent sarcopenia were examined. In a further subgroup (n = 277), associations with knee extensor strength were explored. Longitudinally, predictive value of baseline inflammation on functional decline, physical activity, QoL, and incident sarcopenia was examined. Subgroup analyses were performed in subgroups with chronic inflammation and stratified by age. Linear and logistic regressions were used, adjusted for age, body mass index, centre, and smoking.

Results: At baseline, hs-CRP and WBC were negatively associated with PASE score (hs-CRP: β = -7.920, P < 0.001; and WBC: β = -4.552, P < 0.001) and the physical component score of SF-36 (hs-CRP: β = -1.025, P < 0.001; and WBC: β = -0.364, P < 0.001). Baseline WBC levels were negatively associated with gait speed (β = -0.013; P = 0.025), quadriceps isometric 90° (β = -5.983; P = 0.035) and isokinetic 60°/s peak torque/body weight (β = -5.532; P = 0.027). The prevalence of sarcopenia at baseline was 18.1% (n = 81). Of those without sarcopenia at baseline, 64 (18.6%) satisfied criteria for sarcopenia at follow-up. There were no significant associations between baseline inflammatory markers and either prevalent or incident sarcopenia, or change in level of sarcopenia-defining parameters between baseline and follow-up.

Conclusions: In middle-aged and older men, hs-CRP and WBC were negatively associated with QoL and PASE scores, while WBC was negatively associated with gait speed and knee strength. Associations with hs-CRP remained significant in all ages, whereas WBC levels were only associated with PASE, gait speed and knee strength in older adults (60-79 years). Baseline inflammatory markers (hs-CRP, WBC and albumin) did not predict functional decline, decline in physical activity, decreased QoL or incident sarcopenia.
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http://dx.doi.org/10.1002/jcsm.12785DOI Listing
September 2021

Relevance of nutritional assessment and treatment to counteract cardiac cachexia and sarcopenia in chronic heart failure.

Clin Nutr 2021 09 31;40(9):5141-5155. Epub 2021 Jul 31.

Division of Endocrinology and Nutrition, Complejo Hospitalario Universitario de Santiago (CHUS/SERGAS), Santiago de Compostela, Spain; Epigenomics in Endocrinology and Nutrition Group, Epigenomics Unit, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS/SERGAS), Santiago de Compostela, Spain; CIBER Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Madrid, Spain; Universidade de Santiago de Compostela, Santiago de Compostela, Spain. Electronic address:

Chronic heart failure (CHF) is frequently associated with the involuntary loss of body weight and muscle wasting, which can determine the course of the disease and its prognosis. While there is no gold standard malnutrition screening tool for their detection in the CHF population, several bioelectrical and imaging methods have been used to assess body composition in these patients (such as Dual Energy X-Ray Absorptiometry and muscle ultrasound, among other techniques). In addition, numerous nutritional biomarkers have been found to be useful in the determination of the nutritional status. Nutritional considerations include the slow and progressive supply of nutrients, avoiding high volumes, which could ultimately lead to refeeding syndrome and worsen the clinical picture. If oral feeding is insufficient, hypercaloric and hyperproteic supplementation should be considered. β-Hydroxy-β-methylbutyrate and omega-3 polyunsaturated fatty acid administration prove to be beneficial in certain patients with CHF, and several interventional studies with micronutrient supplementation have also described their possible role in these subjects. Taking into account that CHF is sometimes associated with gastrointestinal dysfunction, parenteral nutritional support may be required in selected cases. In addition, potential therapeutic options regarding nutritional state and muscle wasting have also been tested in clinical studies. This review summarises the scientific evidence that demonstrates the necessity to carry out a careful nutritional evaluation and nutritional treatment to prevent or improve cardiac cachexia and sarcopenia in CHF, as well as improve its course.
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http://dx.doi.org/10.1016/j.clnu.2021.07.027DOI Listing
September 2021

International Multicenter Validation Study of the SAGIT ® Instrument in Acromegaly.

J Clin Endocrinol Metab 2021 Jul 27. Epub 2021 Jul 27.

Pituitary Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Context: The SAGIT ® instrument (SAGIT) has been developed to enable accurate characterization of acromegaly disease activity.

Objective: Evaluate the ability of SAGIT to discriminate between acromegaly disease control status.

Design: Multicenter, non-interventional, prospective and retrospective, longitudinal study.

Settings And Patients: Academic and private clinical practice sites; patients aged ≥18 years with diagnosis of controlled (n=109) or non-controlled (n=105) acromegaly, assessed by clinical global evaluation of disease control (CGE-DC) questionnaire, investigator therapeutic decision and international guidelines. Control status was not determined at baseline for 13 patients. As a limited number of patients were enrolled retrospectively (N=9), all presented analyses are based on the prospective population (N=227).

Methods: Patients were assessed over a two-year follow-up period. Classification and regression tree (CART) analyses were performed to investigate how the SAGIT components at baseline (signs/symptoms [S], associated comorbidities [A], GH levels [G], IGF-1 levels [I], tumor features [T]) discriminate between controlled and non-controlled acromegaly.

Results: Baseline mean subscores S, G, I and T, were significantly lower in patients with CGE-DC controlled acromegaly compared with CGE-DC non-controlled acromegaly. SAGIT components I and G for CGE-DC and S, A, G, I and T for the clinician's therapeutic decision were retained by CART analyses. For international guidelines, only SAGIT component I was retained. The risk for undergoing at least one treatment change during the study for patients with CGE-DC non-controlled acromegaly relative to CGEDC controlled acromegaly was 3.44 times greater.

Conclusion: The SAGIT instrument is a valid and sensitive tool to comprehensively and accurately assess acromegaly severity.
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http://dx.doi.org/10.1210/clinem/dgab536DOI Listing
July 2021

DNA methylome in visceral adipose tissue can discriminate patients with and without colorectal cancer.

Epigenetics 2021 Jul 26:1-12. Epub 2021 Jul 26.

Epigenomics in Endocrinology and Nutrition Group, Epigenomics Unit, Instituto De Investigacion Sanitaria De Santiago De Compostela (IDIS), Complejo Hospitalario Universitario De Santiago De Compostela (CHUS/SERGAS), and Centro De Investigacion Biomedica En Red Fisiopatologia De La Obesidad Y Nutricion (Ciberobn), Spain.

Adipose tissue dysfunction, particularly the visceral (VAT) compartment, has been proposed to play a relevant role in colorectal cancer (CRC) development and progression. Epigenetic mechanisms could be involved in this association. The current study aimed to evaluate if specific epigenetic marks in VAT are associated with colorectal cancer (CRC) to identify epigenetic hallmarks of adipose tissue-related CRC. Epigenome-wide DNA methylation was evaluated in VAT from 25 healthy participants and 29 CRC patients, using the Infinium HumanMethylation450K BeadChip. The epigenome-wide methylation analysis identified 170,184 sites able to perfectly separate the CRC and healthy samples. The differentially methylated CpG sites (DMCpGs) showed a global trend for increased methylated levels in CRC with respect to healthy group. Most of the genes encoded by the DMCpGs belonged to metabolic pathways and cell cycle, insulin resistance, and adipocytokine signalling, as well as tumoural transformation processes. In gene-specific analyses, involved genes biologically relevant for the development of CRC include and . The methylation level of some of them showed a discriminatory capacity for detecting CRC higher than 90%, showing to have the highest capacity. This study reveals that a specific methylation pattern of VAT is associated with CRC. Some of the epigenetic marks identified could provide useful tools for the prediction and personalized treatment of CRC connected to excess adiposity.
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http://dx.doi.org/10.1080/15592294.2021.1950991DOI Listing
July 2021

An Epigenetic Signature is Associated with Serum 25-Hydroxyvitamin D in Colorectal Cancer Tumors.

Mol Nutr Food Res 2021 09 3;65(18):e2100125. Epub 2021 Aug 3.

Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Institute of Biomedical Research in Malaga (IBIMA), University of Malaga, Malaga, 29016, Spain.

Introduction: Vitamin D has been widely associated with colorectal cancer (CRC) through different insights. This study aims to explore the association between serum 25-hydroxyvitamin D (25(OH)D) and the global DNA methylation in tumor from CRC patients.

Methods And Results: A genome-wide DNA methylation analysis is conducted in 20 CRC patients under categorical (10 patients have 25(OH)D <30 ng mL ; 10 patients with 25(OH)D ≥30 ng mL ) and continuous models of 25(OH)D. A total of 95 differentially methylated CpGs (DMCpGs) are detected under the categorical model (false discovery rate (FDR) < 0.05), while 16 DMCpGs are found under the continuous model. Regional analysis showed eight vitamin D-associated differentially methylated regions (DMR). Between them, a DMR is the most significant at cAMP-Dependent Protein Kinase Inhibitor Alpha (PKIA) locus. Furthermore, seven genes, including PKIA gene, have more or equal than two significant DMCpGs. The protein networking analysis found pathways implicated in cell adhesion and extracellular matrix, as well as signaling transduction.

Conclusions: This study identifies novel epigenetic loci associated with serum 25(OH)D status. Interestingly, also, a positive association between vitamin D and DNA methylation in the CRC context is found, suggesting a role in CRC. Further studies are warranted to clarify and replicate these results.
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http://dx.doi.org/10.1002/mnfr.202100125DOI Listing
September 2021

Epigenetic landscape in blood leukocytes following ketosis and weight loss induced by a very low calorie ketogenic diet (VLCKD) in patients with obesity.

Clin Nutr 2021 06 21;40(6):3959-3972. Epub 2021 May 21.

Molecular and Cellular Endocrinology Group. Instituto de Investigacion Sanitaria de Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago de Compostela (CHUS) and Santiago de Compostela University (USC), Spain; CIBER Fisiopatologia de La Obesidad y Nutricion (CIBERobn), Spain.

Background: The molecular mechanisms underlying the potential health benefits of a ketogenic diet are unknown and could be mediated by epigenetic mechanisms.

Objective: To identify the changes in the obesity-related methylome that are mediated by the induced weight loss or are dependent on ketosis in subjects with obesity underwent a very-low calorie ketogenic diet (VLCKD).

Methods: Twenty-one patients with obesity (n = 12 women, 47.9 ± 1.02 yr, 33.0 ± 0.2 kg/m) after 6 months on a VLCKD and 12 normal weight volunteers (n = 6 women, 50.3 ± 6.2 yrs, 22.7 ± 1.5 kg/m) were studied. Data from the Infinium MethylationEPIC BeadChip methylomes of blood leukocytes were obtained at time points of ketotic phases (basal, maximum ketosis, and out of ketosis) during VLCKD (n = 10) and at baseline in volunteers (n = 12). Results were further validated by pyrosequencing in representative cohort of patients on a VLCKD (n = 18) and correlated with gene expression.

Results: After weight reduction by VLCKD, differences were found at 988 CpG sites (786 unique genes). The VLCKD altered methylation levels in patients with obesity had high resemblance with those from normal weight volunteers and was concomitant with a downregulation of DNA methyltransferases (DNMT)1, 3a and 3b. Most of the encoded genes were involved in metabolic processes, protein metabolism, and muscle, organ, and skeletal system development. Novel genes representing the top scoring associated events were identified, including ZNF331, FGFRL1 (VLCKD-induced weight loss) and CBFA2T3, C3orf38, JSRP1, and LRFN4 (VLCKD-induced ketosis). Interestingly, ZNF331 and FGFRL1 were validated in an independent cohort and inversely correlated with gene expression.

Conclusions: The beneficial effects of VLCKD therapy on obesity involve a methylome more suggestive of normal weight that could be mainly mediated by the VLCKD-induced ketosis rather than weight loss.
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http://dx.doi.org/10.1016/j.clnu.2021.05.010DOI Listing
June 2021

Self-Reported Shorter Than Desired Ejaculation Latency and Related Distress-Prevalence and Clinical Correlates: Results From the European Male Ageing Study.

J Sex Med 2021 05 2;18(5):908-919. Epub 2021 Apr 2.

Endocrinology Unit, Mario Serio" Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy. Electronic address:

Background: Few data have looked at the occurrence and clinical correlates of self-reported shorter than desired ejaculation latency (rapid ejaculation, RE) and its related distress in the general population.

Aim: To determine the prevalence and clinical correlates of self-reported RE and RE- related distress in middle age and older European men.

Methods: Subjects were recruited from population samples of men aged 40-79 years across 8 European centers.

Outcomes: Self-reported RE and its related distress were derived from the European male Aging Study (EMAS) sexual function questionnaire (EMAS-SFQ). Beck's depression Inventory (BDI) was used for the quantification of depressive symptoms, the Short Form 36 health survey (SF-36) for the assessment of the quality of life, the International Prostate Symptom Score (IPSS) for the evaluation of lower urinary tract symptoms.

Results: About 2,888 community dwelling men aged 40-79 years old (mean 58.9 ± 10.8 years) were included in the analysis. Among the subjects included, 889 (30.8%) self-reported RE. Among them, 211 (7.3%) claimed to be distressed (5.9% and 1.4% reported mild or moderate-severe distress, respectively). Increasing levels of RE-related distress were associated with a progressive worse sexual functioning, higher risk of ED and with couple impairment, along with a higher prevalence of depressive symptoms (all P < 0.05). Furthermore, a worse quality of life and higher IPSS score were associated with RE-related distress (all P < 0.05). The aforementioned results were confirmed even when patients using drugs possibly interfering with ejaculation or those without a stable relationship were excluded from the analysis.

Clinical Implications: RE is a frequent condition in men from the general population; however, its related distress is relatively modest. Nonetheless, men with any degree of self-reported RE show increasing levels of depression, worse quality of life and worse couple satisfaction.

Strengths & Limitations: This is the first study estimating the prevalence of self-reported RE and its related distress, along with their biological and psychological correlates, in a population sample of European middle age and older men. However, is should be recognized that the diagnosis of RE was derived from patient reports and not supported by Intra-ejaculatory-Latency-Time (IELT) measurements.

Conclusion: Self-reported RE is relatively common in European men aged more than 40 years. The reported limited RE-related distress may explain the relatively low number of medical consultations for RE. RE-related distress is associated with worse sexual function, couple impairment, and more LUTS resulting in a worse quality of life and mood disturbances. Corona G, Rastrelli G, Bartfai G, et al. Self-Reported Shorter Than Desired Ejaculation Latency and Related Distress-Prevalence and Clinical Correlates: Results From the European Male Ageing Study. J Sex Med Rev 2021;18:908-919.
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http://dx.doi.org/10.1016/j.jsxm.2021.01.187DOI Listing
May 2021

Variable Expressivity in Type 2 Familial Partial Lipodystrophy Related to R482 and N466 Variants in the LMNA Gene.

J Clin Med 2021 Mar 18;10(6). Epub 2021 Mar 18.

UETeM-Molecular Pathology Group, Department of Psychiatry, Radiology, Public Health, Nursing and Medicine, IDIS-CIMUS, University of Santiago de Compostela, 15706 Santiago de Compostela, Spain.

Patients with Dunnigan disease (FPLD2) with a pathogenic variant affecting exon 8 of the gene are considered to have the classic disease, whereas those with variants in other exons manifest the "atypical" disease. The aim of this study was to investigate the degree of variable expressivity when comparing patients carrying the R482 and N466 variants in exon 8. Thus, 47 subjects with FPLD2 were studied: one group of 15 patients carrying the N466 variant and the other group of 32 patients with the R482 variant. Clinical, metabolic, and body composition data were compared between both groups. The thigh skinfold thickness was significantly decreased in the R482 group in comparison with the N466 group (4.2 ± 1.8 and 5.6 ± 2.0 mm, respectively, = 0.002), with no other differences in body composition. Patients with the N466 variant showed higher triglyceride levels (177.5 [56-1937] vs. 130.0 [55-505] mg/dL, = 0.029) and acute pancreatitis was only present in these subjects (20%). Other classic metabolic abnormalities related with the disease were present regardless of the pathogenic variant. Thus, although FPLD2 patients with the R482 and N466 variants share most of the classic characteristics, some phenotypic and metabolic differences suggest possible heterogeneity even within exon 8 of the gene.
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http://dx.doi.org/10.3390/jcm10061259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002937PMC
March 2021

Pituitary Neoplasm Nomenclature Workshop: Does Adenoma Stand the Test of Time?

J Endocr Soc 2021 Mar 9;5(3):bvaa205. Epub 2021 Feb 9.

Royal Veterinary College, University of London, London, UK.

The designates pituitary neoplasms as adenomas. A proposed nomenclature change to pituitary neuroendocrine tumors (PitNETs) has been met with concern by some stakeholder groups. The Pituitary Society coordinated the Pituitary Neoplasm Nomenclature (PANOMEN) workshop to address the topic. Experts in pituitary developmental biology, pathology, neurosurgery, endocrinology, and oncology, including representatives nominated by the Endocrine Society, European Society of Endocrinology, European Neuroendocrine Association, Growth Hormone Research Society, and International Society of Pituitary Surgeons. Clinical epidemiology, disease phenotype, management, and prognosis of pituitary adenomas differ from that of most NETs. The vast majority of pituitary adenomas are benign and do not adversely impact life expectancy. A nomenclature change to PitNET does not address the main challenge of prognostic prediction, assigns an uncertain malignancy designation to benign pituitary adenomas, and may adversely affect patients. Due to pandemic restrictions, the workshop was conducted virtually, with audiovisual lectures and written précis on each topic provided to all participants. Feedback was collated and summarized by Content Chairs and discussed during a virtual writing meeting moderated by Session Chairs, which yielded an evidence-based draft document sent to all participants for review and approval. There is not yet a case for adopting the PitNET nomenclature. The PANOMEN Workshop recommends that the term adenoma be retained and that the topic be revisited as new evidence on pituitary neoplasm biology emerges.
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http://dx.doi.org/10.1210/jendso/bvaa205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874572PMC
March 2021

The Southern European Atlantic diet.

Minerva Endocrinol (Torino) 2021 Jun 19;46(2):145-160. Epub 2020 Nov 19.

Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain.

The Southern Europe Atlantic Diet (SEAD) is the traditional diet consumed in the Northwestern region of the Iberian Peninsula: Galicia (Spain) and North of Portugal. These regions have geographical, climatic and cultural characteristics that had led them to develop their own dietary pattern. This dietary pattern integrated into its environment is based on fresh, local and seasonal products intake. In this diet there is a high intake of fish, seafood, cereals, potatoes, legumes, fruits, dairy products and vegetables. Meat, preferably lean meat, is consume moderately as well as eggs and wine. SEAD is more than a diet, it is a lifestyle where exercise, simples cooking techniques, respect for the traditions and pleasure of eating accompanied are constants. Although this pattern has been known for centuries, it did not begin to be define as such until the signing of "Baione Declaration" in 2006. Some bioactive compounds of SEAD had showed health benefits and protect against acute myocardial infarction. Data supports that SEAD is a sustainable diet. In the presented review, results of studies on the SEAD are presented and discussed. Also, a recent proposal of SEAD Index is reported. Therefore, SEAD should be considered as an excellent dietary pattern and lifestyle.
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http://dx.doi.org/10.23736/S0391-1977.20.03381-7DOI Listing
June 2021

Very-low-calorie ketogenic diet for the management of obesity, overweight and related disorders.

Minerva Endocrinol (Torino) 2021 Jun 19;46(2):161-167. Epub 2020 Nov 19.

Clinic for Endocrine and Metabolic Disorders, Ente Ospedaliero Cantonale (EOC), Bellinzona, Switzerland.

Introduction: Very-low-calorie ketogenic diet (VLCKD) is a promising lifestyle intervention for the management of overweight and obesity. It is characterized by a restriction of both calories and carbohydrates, while assuring the adequate proteins, fats and micronutrients intake. Significant results in terms of excess body weight loss have been reported and this strategy considered also in the preoperative settings. Improvements in hypertension, type 2 diabetes and dyslipidemia follows.

Evidence Acquisition: PubMed and Google Scholar were searched for papers reporting data on VLCKD as a strategy for the management of overweight, obesity and related disorders in adults.

Evidence Synthesis: Four main documents are available in the literature and were included in the present narrative review.

Conclusions: The present review discusses available evidence and provides practical recommendations for the management of VLCKD.
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http://dx.doi.org/10.23736/S0391-1977.20.03356-8DOI Listing
June 2021

Commentary: Nonalcoholic or metabolic dysfunction-associated fatty liver disease? The epidemic of the 21st century in search of the most appropriate name.

Metabolism 2020 12 22;113:154413. Epub 2020 Oct 22.

Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, MA, USA; Department of Internal Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. Electronic address:

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http://dx.doi.org/10.1016/j.metabol.2020.154413DOI Listing
December 2020

Multidisciplinary management of acromegaly: A consensus.

Rev Endocr Metab Disord 2020 12 10;21(4):667-678. Epub 2020 Sep 10.

Medical Research Unit in Endcrine Diseases, Hospital de Especialidades, Centro Médico Nacional, Siglo XXI, IMSS, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico.

The 13th Acromegaly Consensus Conference was held in November 2019 in Fort Lauderdale, Florida, and comprised acromegaly experts including endocrinologists and neurosurgeons who considered optimal approaches for multidisciplinary acromegaly management. Focused discussions reviewed techniques, results, and side effects of surgery, radiotherapy, and medical therapy, and how advances in technology and novel techniques have changed the way these modalities are used alone or in combination. Effects of treatment on patient outcomes were considered, along with strategies for optimizing and personalizing therapeutic approaches. Expert consensus recommendations emphasize how best to implement available treatment options as part of a multidisciplinary approach at Pituitary Tumor Centers of Excellence.
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http://dx.doi.org/10.1007/s11154-020-09588-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7942783PMC
December 2020

Ketogenic diets as treatment of obesity and type 2 diabetes mellitus.

Rev Endocr Metab Disord 2020 Sep;21(3):381-397

Division of Endocrinology, Department of Medicine, Santiago de Compostela University (USC), Complejo Hospitalario Universitario de Santiago, Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago, Spain.

During the last decades, several interventions for the management of overweight and obesity have been proposed. Among diets, the first studies focused on the effect of water only and total fasting diets with or without proteins. Unfortunately, they were found to be associated with adverse events which lead to the abandon of these strategies. Interestingly, despite the radical approach, total fasting was effective and generally well tolerated. A strict connection between protein-calorie malnutrition and increased in morbidity and mortality in hospitalized patients was found at that time. Then, the seminal works of Blackburn and his collaborators lead to the introduction of the protein-sparing modified fast. Encouraged by the early results using this intervention, diets evolved to the current very-low-calorie ketogenic diets (VLCKD). In the present review, results of studies on the VLCKDs are presented and discussed, with a particular reference to the protocolled VLCKD. Also, a recent proposal on the nomenclature on the ketogenic diets is reported. Available evidence suggests VLCKDs to be effective in achieving a rapid and significant weight loss by means of an easily reversible intervention which could be repeated, if needed. Muscle mass and strength are preserved, resting metabolic rate is not impaired, hunger, appetite and mood are not worsened. Symptoms and abnormal laboratory findings can be there, but they have generally been reported as of mild intensity and transient. Preliminary studies suggest VLCKDs to be a potential game-changer in the management of type 2 diabetes too. Therefore, VLCKDs should be considered as an excellent initial step in properly selected and motivated patients with obesity or type 2 diabetes, to be delivered as a part of a multicomponent strategy and under strict medical supervision.
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http://dx.doi.org/10.1007/s11154-020-09580-7DOI Listing
September 2020

Analysis of platelets from a diet-induced obesity rat model: elucidating platelet dysfunction in obesity.

Sci Rep 2020 08 4;10(1):13104. Epub 2020 Aug 4.

Platelet Proteomics Group, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade Santiago de Compostela, Avda de Barcelona s/n, 15782, Santiago de Compostela, Spain.

Obesity is one of the main health problems in industrialized countries. The contribution of multiple factors developed in obesity can hardly be modeled in vitro. In this context, the development of animal models mimicking human obesity could be essential. The aim of the present study was to compare platelets from a diet-induced obesity (DIO) rat model with their lean control group in order to elucidate platelet dysfunction mechanisms in obesity and correlate the results with previous data from morbid obese patients. In parallel, we also established a blood collection and platelet isolation methodology to study the DIO rat model at biochemical and functional level. Optimal blood collection was obtained from vena cava and platelet isolation was based on a serial of centrifugations avoiding platelet activation. Our results show that the DIO rat model simulate obesity pathologically since weight gain, fasting glucose and platelet counts are increased in obese rats. Interestingly, platelet levels of the active form of Src (pTyr) showed a tendency to increase in DIO rats pointing towards a potential dysfunction in Src family kinases-related signalling pathways in obesity. Moreover, platelets from DIO rats adhere more to collagen compared with the control group, pointing towards Glycoprotein VI (GPVI) as one of the dysregulated receptors in obesity, in agreement with our recent studies in humans. These results confirm that obesity, in line with human studies, present a platelet dysregulation, and highlight the relevance of considering novel antithrombotic drug targets in these patients, such as GPVI.
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http://dx.doi.org/10.1038/s41598-020-70162-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403150PMC
August 2020

Pituitary Tumors Centers of Excellence.

Endocrinol Metab Clin North Am 2020 09 15;49(3):553-564. Epub 2020 Jul 15.

Division of Endocrinology, Complejo Hospitalario Universitario de Santiago (USC/SERGAS), Instituto de Investigacion Sanitaria de Santiago (IDIS), Rúa da Choupana, S/N, Santiago de Compostela, A Coruña 15706, Spain; CIBER Fisiopatología de la Obesidad y la Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain. Electronic address:

Pituitary tumors are common and require complex and sophisticated procedures for both diagnosis and therapy. To maintain the highest standards of quality, it is proposed to manage patients in pituitary tumors centers of excellence (PTCOEs) with patient-centric organizations, with expert clinical endocrinologists and neurosurgeons forming the core. That core needs to be supported by experts from different disciplines such as neuroradiology, neuropathology, radiation oncology, neuro-ophthalmology, otorhinolaryngology, and trained nursing. To provide high-level medical care to patients with pituitary tumors, PTCOEs further pituitary science through research publication, presentation of results at meetings, and performing clinical trials.
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http://dx.doi.org/10.1016/j.ecl.2020.05.010DOI Listing
September 2020

Weight loss normalizes enhanced expression of the oncogene survivin in visceral adipose tissue and blood leukocytes from individuals with obesity.

Int J Obes (Lond) 2021 01 16;45(1):206-216. Epub 2020 Jun 16.

Epigenomics in Endocrinology and Nutrition Group, Instituto de Investigacion Sanitaria (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS/SERGAS), Santiago de Compostela, Spain.

Background/objectives: Survivin is an oncogene associated with a decrease in apoptosis, an increase in tumor growth, and poor clinical outcome of diverse malignancies. A correlation between obesity, cancer, and survivin is reported in the literature. To date, the impact of weight loss on change in survivin levels is understudied. This study was aimed at: (1) comparing survivin levels in adipose tissue (AT) from lean and obese animal models and evaluating changes after weight loss induced by energy restriction and/or exercise; (2) comparing survivin levels in normal weighted and obese humans and evaluating changes in survivin levels after weight loss induced by a very-low-calorie ketogenic diet (VLCKD) or bariatric surgery in AT and/or blood leukocytes (PBL/PBMCs).

Subjects/methods: Survivin expression was evaluated in subcutaneous (SAT) and visceral (VAT) AT derived from animal models of monogenic (Zucker rats) and diet-induced obesity (Sprague Dawley rats and C57BL/6J mice) and after a 4-week weight-loss protocol of energy restriction and/or exercise. Plasma was used to measure the inflammatory status. Survivin expression was also evaluated in PBMCs from patients with obesity and compared with normal weight, in PBLs after VLCKD, and in SAT and/or PBLs after bariatric surgery.

Results: Survivin expression was specifically higher in VAT from obese that lean animals, without differences in SAT. It decreased after weight loss induced by energy restriction and correlated with adiposity and inflammatory markers. In humans, the correlation between being obese and higher levels of survivin was confirmed. In obese subjects, survivin levels were reduced following weight loss after either VLCKD or bariatric surgery. Particularly, a decrease in PBMCs expression (not in SAT one) was found after surgery.

Conclusions: Weight loss is effective in decreasing survivin levels. Also, PBL/PBMC should be regarded as appropriate mirror of survivin levels in VAT for the identification of an obesity-related protumoral microenvironment.
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http://dx.doi.org/10.1038/s41366-020-0630-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752753PMC
January 2021

Association between variation of circulating 25-OH vitamin D and methylation of secreted frizzled-related protein 2 in colorectal cancer.

Clin Epigenetics 2020 06 9;12(1):83. Epub 2020 Jun 9.

Deparment of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Institute of Biomedical Research in Malaga (IBIMA) and University of Malaga, Malaga, Spain.

Backgrounds: Colorectal cancer (CRC) results from the accumulation of epigenetic and genetic changes in colon cells during neoplasic transformation, which the activation of Wingless (Wnt) signaling pathway is a common mechanism for CRC initiation. The Wnt pathway is mainly regulated by Wnt antagonists, as secreted frizzled-related protein (SFRP) family. Indeed, SFRP2 is proposed as a noninvasive biomarker for CRC diagnosis. Vitamin D also antagonizes Wnt signaling in colon cancers cells. Several studies showed that vitamin D was able to alter DNA methylation, although this mechanism is not yet clear. Therefore, the aim of this study was to find an association between circulating 25-OH vitamin D (30th percentile of vitamin D) and the SFRP2 methylation.

Methods: A total of 67 CRC patients were included in the study. These patients were subdivided into two groups based on their 30th percentile vitamin D (20 patients were below, and 47 participants were above the 30th percentile of vitamin D). We investigated the SFRP2 methylation in peripheral blood mononuclear cells (PBMCs), visceral adipose tissue (VAT), CRC tumor tissue, and adjacent tumor-free area. We also determined the relationship between SFRP2 methylation and methylation of carcinogenic and adipogenic genes. Finally, we tested the effect of vitamin D on the SFRP2 methylation in human colorectal carcinoma cell lines 116 (HCT116) and studied the association of neoadjuvant therapy under the 30th percentile vitamin D with SFRP2 promoter methylation.

Results: SFRP2 methylation in tumor area was decreased in patients who had higher levels of vitamin D. SFRP2 promoter methylation was positively correlated in tumor area with insulin and homeostasis model assessment of insulin resistance (HOMA-IR) but negatively correlated with HDL-c. SFRP2 methylation was also correlated with T cell lymphoma invasion and metastasis 1 (TIAM1) methylation in tumor area and CCAAT/enhancer-binding protein alpha (C/EBPα) in VAT. Treatment with vitamin D did not affect SFRP2 methylation in HCT116 cell line. Finally, neoadjuvant treatment was correlated with higher circulating 25-OH vitamin D and SFRP2 methylation under linear regression model.

Conclusion: Our results showed that higher circulating vitamin D is associated with low SFRP2 promoter methylation. Therefore, our results could suggest that vitamin D may have an epigenetic effect on DNA methylation. Finally, higher vitamin D could contribute to an improvement response to neoadjuvant treatment.
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http://dx.doi.org/10.1186/s13148-020-00875-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7285750PMC
June 2020

Methylation Levels in Leukocytes From Women With Breast Cancer Is Modulated by Adiposity, Menopausal State, and the Mediterranean Diet.

Front Endocrinol (Lausanne) 2020 23;11:245. Epub 2020 Apr 23.

Laboratory of Epigenomics in Endocrinology and Nutrition (EpiEndoNut), Instituto de Investigacion Sanitaria de Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago de Compostela (CHUS/SERGAS), Santiago de Compostela, Spain.

The methylation levels of in breast tumors has been previously identified as a possible epigenetic mark of breast cancer associated with obesity. The aim of the current study was to investigate differences in methylation levels of depending on obesity, menopausal state and dietary pattern in blood leukocytes, a non-invasive sample. The methylation levels of of two CpG sites (CpGs) located in promoter and island previously identified as differentially methylated according to adiposity and menopausal state by 450 k array (cg10635122, cg03562414) were evaluated by pyrosequencing in DNA from the blood leukocytes of breast cancer patients [ = 90; = 64 (71.1%) overweight/obesity and = 26 (28.9%) normal-weight] and paired tumor tissue biopsies ( = 8 breast cancer patients with obesity; = 3/5 premenopausal/postmenopausal women). Differences in methylation levels were evaluated at each CpGs individually and at the mean of the two evaluated CpGs. Adherence to the Mediterranean diet was evaluated using the MEDAS-validated questionnaire, and the consumption of food groups of interest was also evaluated using the recommended intakes of the . The methylation levels of were correlated between paired leukocytes and breast tumor biopsies ( = 0.62; = 0.001). Moreover, higher methylation was found in leukocytes from patients with obesity ( = 0.002) and postmenopausal patients ( = 0.022) than patients with normal-weight or premenopausal, respectively. After adjusting for the body mass index and age, higher levels of methylation were also found in women with greater adherence to the Mediterranean diet ( = 0.017) or specific foods. Relevantly, the methylation levels of showed a good ability for fish consumption detection [area under the ROC curve (AUC) = 0.72; = 0.016]. In conclusion, the association between methylation of and adiposity, menopausal state, and adherence to the Mediterranean diet can be detected in the blood leukocytes. The results guarantee the need of performing further studies in longer longitudinal cohorts in order to elucidate the role of methylation in the association between breast cancer, adiposity and dietary patterns.
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http://dx.doi.org/10.3389/fendo.2020.00245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191069PMC
May 2021

Vesicles Shed by Pathological Murine Adipocytes Spread Pathology: Characterization and Functional Role of Insulin Resistant/Hypertrophied Adiposomes.

Int J Mol Sci 2020 03 24;21(6). Epub 2020 Mar 24.

Grupo Obesidómica, Área de Endocrinología, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Xerencia de Xestión Integrada de Santiago (XXIS/SERGAS), 15706 Santiago de Compostela, Spain.

Extracellular vesicles (EVs) have recently emerged as a relevant way of cell to cell communication, and its analysis has become an indirect approach to assess the cell/tissue of origin status. However, the knowledge about their nature and role on metabolic diseases is still very scarce. We have established an insulin resistant (IR) and two lipid (palmitic/oleic) hypertrophied adipocyte cell models to isolate EVs to perform a protein cargo qualitative and quantitative Sequential Window Acquisition of All Theoretical Mass Spectra (SWATH) analysis by mass spectrometry. Our results show a high proportion of obesity and IR-related proteins in pathological EVs; thus, we propose a panel of potential obese adipose tissue EV-biomarkers. Among those, lipid hypertrophied vesicles are characterized by ceruloplasmin, mimecan, and perilipin 1 adipokines, and those from the IR by the striking presence of the adiposity and IR related transforming growth factor-beta-induced protein ig-h3 (TFGBI). Interestingly, functional assays show that IR and hypertrophied adipocytes induce differentiation/hypertrophy and IR in healthy adipocytes through secreted EVs. Finally, we demonstrate that lipid atrophied adipocytes shed EVs promote macrophage inflammation by stimulating IL-6 and TNFα expression. Thus, we conclude that pathological adipocytes release vesicles containing representative protein cargo of the cell of origin that are able to induce metabolic alterations on healthy cells probably exacerbating the disease once established.
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http://dx.doi.org/10.3390/ijms21062252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139903PMC
March 2020

Confusion in the nomenclature of ketogenic diets blurs evidence.

Rev Endocr Metab Disord 2020 03;21(1):1-3

Division of Endocrinology, Santiago de Compostela University and CIBEROBN, Santiago de Compostela, Spain.

Ketogenic diets have been proposed as a non-pharmacological strategy for the management of several chronic conditions. Their efficacy and safety have been evaluated in the field of neurology, oncology and endocrinology for disorders including cancer, dementia, drug-resistant epilepsy, migraines, obesity, polycystic ovary syndrome and type 2 diabetes mellitus. The nutritional requirements of these subjects are expected to differ significantly. Indeed, although all ketogenic diets restrict carbohydrates, each intervention is characterized by a specific daily calorie intake, macronutrient composition and duration. However, the adopted nomenclature was often unclear to the general reader; also, the same abbreviations for different protocols were used. This possibly resulted in mistakes in the interpretation of the available evidence and limited the impact of studies on the topic in the clinical practice. Adopting a clear and consistent vocabulary is key in any context. Here, we present a practical and clinically-based proposal for the classification and abbreviation of ketogenic diets.
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http://dx.doi.org/10.1007/s11154-020-09546-9DOI Listing
March 2020

An energy restriction-based weight loss intervention is able to reverse the effects of obesity on the expression of liver tumor-promoting genes.

FASEB J 2020 02 16;34(2):2312-2325. Epub 2019 Dec 16.

Laboratory of Epigenomics in Endocrinology and Nutrition, Instituto de Investigacion Sanitaria de Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago de Compostela (CHUS/SERGAS), Santiago de Compostela, Spain.

The epidemiological evidence regarding the association of obesity with liver disease and possibly hepatocellular carcinoma highlights the need for investigations of whether obesity itself could induce the differential expression of genes commonly associated with the initial phase of liver tumorigenesis, and whether such phenomenon could be reversed after a weight loss intervention. In this study, obese Zucker rats were found to have dysregulated cell proliferation, antioxidative defenses, and tumor suppressor gene expression in association with liver dysfunction parameters, as well as oxidative stress and inflammation. Importantly, after a 4-week weight loss protocol of energy restriction and/or exercise, this effect on the liver carcinogenesis-related genes was reversed concomitantly with reductions in the fat mass, hepatic lipid content, oxidative stress, and inflammation. The findings indicate that the oxidative stress and inflammation associated with excess adiposity promote dysregulation of the genes involved in liver tumorigenesis. This is clinically relevant because these effects were detectable in the liver without evidence of a tumoral mass and were reversed after weight loss. Consequently, this study reveals the susceptibility of obese individuals to the initiation of a hepatocarcinogenic process, and how this can be prevented by achieving a healthy body weight.
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http://dx.doi.org/10.1096/fj.201901147RRDOI Listing
February 2020

Leptin, Obesity, and Leptin Resistance: Where Are We 25 Years Later?

Nutrients 2019 Nov 8;11(11). Epub 2019 Nov 8.

CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Instituto Salud Carlos III, 28029 Madrid, Spain.

Leptin, a hormone that is capable of effectively reducing food intake and body weight, was initially considered for use in the treatment of obesity. However, obese subjects have since been found to have high levels of circulating leptin and to be insensitive to the exogenous administration of leptin. The inability of leptin to exert its anorexigenic effects in obese individuals, and therefore, the lack of clinical utility of leptin in obesity, is defined as leptin resistance. This phenomenon has not yet been adequately characterized. Elucidation of the molecular mechanisms underlying leptin resistance is of vital importance for the application of leptin as an effective treatment for obesity. Leptin must cross the blood-brain barrier (BBB) to reach the hypothalamus and exert its anorexigenic functions. The mechanisms involved in leptin transportation across the blood-brain barrier continue to be unclear, thereby preventing the clinical application of leptin in the treatment of obesity. In recent years, new strategies have been developed to recover the response to leptin in obesity. We have summarized these strategies in this review.
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http://dx.doi.org/10.3390/nu11112704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893721PMC
November 2019

A Consensus on the Diagnosis and Treatment of Acromegaly Comorbidities: An Update.

J Clin Endocrinol Metab 2020 04;105(4)

Department of Medicine, CIBERER, Universidad Autónoma de Madrid, Madrid, Spain.

Objective: The aim of the Acromegaly Consensus Group was to revise and update the consensus on diagnosis and treatment of acromegaly comorbidities last published in 2013.

Participants: The Consensus Group, convened by 11 Steering Committee members, consisted of 45 experts in the medical and surgical management of acromegaly. The authors received no corporate funding or remuneration.

Evidence: This evidence-based consensus was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence following critical discussion of the current literature on the diagnosis and treatment of acromegaly comorbidities.

Consensus Process: Acromegaly Consensus Group participants conducted comprehensive literature searches for English-language papers on selected topics, reviewed brief presentations on each topic, and discussed current practice and recommendations in breakout groups. Consensus recommendations were developed based on all presentations and discussions. Members of the Scientific Committee graded the quality of the supporting evidence and the consensus recommendations using the GRADE system.

Conclusions: Evidence-based approach consensus recommendations address important clinical issues regarding multidisciplinary management of acromegaly-related cardiovascular, endocrine, metabolic, and oncologic comorbidities, sleep apnea, and bone and joint disorders and their sequelae, as well as their effects on quality of life and mortality.
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http://dx.doi.org/10.1210/clinem/dgz096DOI Listing
April 2020

Effect of a Very-Low-Calorie Ketogenic Diet on Circulating Myokine Levels Compared with the Effect of Bariatric Surgery or a Low-Calorie Diet in Patients with Obesity.

Nutrients 2019 Oct 4;11(10). Epub 2019 Oct 4.

Division of Endocrinology, Department of Medicine, Complejo Hospitalario Universitario de Santiago (CHUS/SERGAS), Instituto de Investigacion Sanitaria de Santiago (IDIS), 15706 Santiago de Compostela, Spain.

The preservation of muscle mass and muscle function after weight loss therapy is currently a considerable challenge in the fight against obesity. Muscle mass secretes proteins called myokines that have relevant functions in the regulation of metabolism and health. This study was aimed to evaluate whether a very low-calorie ketogenic (VLCK) diet may modulate myokine levels, in addition to changes in body composition, compared to a standard, balanced low-calorie (LC) diet or bariatric surgery in patients with obesity. Body composition, ketosis, insulin sensitivity and myokines were evaluated in 79 patients with overweight/obesity after a therapy to lose weight with a VLCK diet, a LC diet or bariatric surgery. The follow-up was 6 months. The weight loss therapies induced changes in myokine levels in association with changes in body composition and biochemical parameters. The effects on circulating myokine levels compared to those at baseline were stronger after the VLCK diet than LC diet or bariatric surgery. Differences reached statistical significance for IL-8, MMP2 and irisin. In conclusion, nutritional interventions or bariatric surgery to lose weight induces changes in circulating myokine levels, being this effect potentially most notable after following a VLCK diet.
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http://dx.doi.org/10.3390/nu11102368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6835835PMC
October 2019

Data on hyper-activation of GPVI signalling in obese patients: Towards the identification of novel antiplatelet targets in obesity.

Data Brief 2019 Apr 28;23:103784. Epub 2019 Feb 28.

Platelet Proteomics Group, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade Santiago de Compostela, Spain.

This data article is associated with the manuscript "GPVI surface expression and signalling pathway activation are increased in platelets from obese patients: elucidating potential anti-atherothrombotic targets in obesity" [1]. The study refers to a combination of different approaches in order to identify platelet-derived biomarkers in obesity. A total of 34 obese patients and their lean-matched controls were included in the study. We carried out a proteomic and functional (aggregation assays) analysis to find alterations in platelet-derived signalling pathways. After that, biochemical and mechanistic (flow cytometry assays) approaches were done in order to confirm a hyperactivation of the GPVI-related signalling pathway.
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http://dx.doi.org/10.1016/j.dib.2019.103784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6661234PMC
April 2019

Staging and managing patients with acromegaly in clinical practice: baseline data from the SAGIT® validation study.

Pituitary 2019 Oct;22(5):476-487

Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Purpose: The SAGIT® instrument, designed to assist clinicians to stage acromegaly, assess treatment response and adapt patient management, was well received by endocrinologists in a pilot study. We report an interim analysis of baseline data from the validation phase.

Methods: The SAGIT® validation study (ClinicalTrials.gov NCT02539927) is an international, non-interventional study. Data collection included: demographic/disease characteristics; medical/surgical histories; concomitant acromegaly treatments; investigators' subjective evaluation of disease-control status (clinical global evaluation of disease control [CGE-DC]; controlled/not controlled/yet to be clarified) and clinical disease activity (active/not active); growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels; investigators' therapeutic decision.

Results: Of 228 patients enrolled, investigators considered disease to be controlled in 110 (48.2%), not controlled in 105 (46.1%), and yet to be clarified in 13 (5.7%) according to CGE-DC. Thirty-three patients were treatment-naïve (not controlled, n = 31; yet to be clarified, n = 2). Investigators considered 48.2% patients in the controlled and 95.2% in the not-controlled groups to have clinically active disease. In the controlled group, 29.7% of patients did not exhibit hormonal control (GH ≤ 2.5 µg/L; normalized IGF-1) and 47.3% did not have rigorous hormonal control (GH < 1.0 µg/L; normalized IGF-1) by contemporary consensus. Current acromegaly treatment was continued with no change for 91.8% of patients in the controlled and 40.0% in the not-controlled groups.

Conclusions: These data highlight discrepancies between investigator-evaluated disease-control status, disease activity, hormonal control, and treatment decisions in acromegaly. Once validated, the SAGIT® instrument may assist clinicians in making active management decisions for patients with acromegaly.
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http://dx.doi.org/10.1007/s11102-019-00977-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6728296PMC
October 2019
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