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1.
Curr Opin Clin Nutr Metab Care ; 27(5): 402-409, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-39022899

ABSTRACT

PURPOSE OF REVIEW: Sarcopenic obesity is a likely common, but certainly underestimated obesity phenotype, with an important negative clinical impact. Its definition and diagnosis have however remained elusive until recently. RECENT FINDINGS: Substantial progress has been recently made in sarcopenic obesity diagnostic tools, with the first international consensus proposed by the European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO). Very encouraging results emerge from initial implementation of the ESPEN-EASO algorithm. In addition, even more recent progress in global consensus on sarcopenia conceptual definition is likely to further enhance consistency in sarcopenic obesity identification. The latter Global Leadership Initiative on Sarcopenia (GLIS) initiative also adopted a new definition of muscle specific strength. Its inclusion in sarcopenia diagnostic constructs opens the possibility of its potential evaluation in sarcopenic obesity, also considering the emerging positive impact of obesity treatment and fat loss on muscle functional parameters. SUMMARY: New consensus tools for sarcopenic obesity diagnosis are likely to improve awareness, understanding, identification and treatment of this under-recognized obesity phenotype.


Subject(s)
Obesity , Sarcopenia , Sarcopenia/diagnosis , Sarcopenia/physiopathology , Humans , Obesity/complications , Obesity/diagnosis , Muscle, Skeletal/physiopathology , Muscle Strength , Consensus , Phenotype
2.
Age Ageing ; 53(3)2024 03 01.
Article in English | MEDLINE | ID: mdl-38520141

ABSTRACT

IMPORTANCE: Sarcopenia, the age-related loss of muscle mass and strength/function, is an important clinical condition. However, no international consensus on the definition exists. OBJECTIVE: The Global Leadership Initiative in Sarcopenia (GLIS) aimed to address this by establishing the global conceptual definition of sarcopenia. DESIGN: The GLIS steering committee was formed in 2019-21 with representatives from all relevant scientific societies worldwide. During this time, the steering committee developed a set of statements on the topic and invited members from these societies to participate in a two-phase International Delphi Study. Between 2022 and 2023, participants ranked their agreement with a set of statements using an online survey tool (SurveyMonkey). Statements were categorised based on predefined thresholds: strong agreement (>80%), moderate agreement (70-80%) and low agreement (<70%). Statements with strong agreement were accepted, statements with low agreement were rejected and those with moderate agreement were reintroduced until consensus was reached. RESULTS: 107 participants (mean age: 54 ± 12 years [1 missing age], 64% men) from 29 countries across 7 continents/regions completed the Delphi survey. Twenty statements were found to have a strong agreement. These included; 6 statements on 'general aspects of sarcopenia' (strongest agreement: the prevalence of sarcopenia increases with age (98.3%)), 3 statements on 'components of sarcopenia' (muscle mass (89.4%), muscle strength (93.1%) and muscle-specific strength (80.8%) should all be a part of the conceptual definition of sarcopenia)) and 11 statements on 'outcomes of sarcopenia' (strongest agreement: sarcopenia increases the risk of impaired physical performance (97.9%)). A key finding of the Delphi survey was that muscle mass, muscle strength and muscle-specific strength were all accepted as 'components of sarcopenia', whereas impaired physical performance was accepted as an 'outcome' rather than a 'component' of sarcopenia. CONCLUSION AND RELEVANCE: The GLIS has created the first global conceptual definition of sarcopenia, which will now serve to develop an operational definition for clinical and research settings.


Subject(s)
Sarcopenia , Male , Humans , Aged , Female , Sarcopenia/diagnosis , Sarcopenia/epidemiology , Delphi Technique , Consensus , Leadership , Muscle Strength/physiology
3.
Eat Weight Disord ; 29(1): 51, 2024 Aug 04.
Article in English | MEDLINE | ID: mdl-39097845

ABSTRACT

The transition to adult health care (HCT, Health Care Transition), is the purposeful, planned movement of patients from paediatric to adult services. For the adolescent living with obesity (ALwO), the HCT represents a crucial window for effective intervention that can help improve body weight, adiposopathy, and metabolic complications. Nevertheless, no transition guidelines, models, and tools have been developed for these patients. The present statement of the Italian Society of Obesity examines the critical transition of ALwO from paediatric to adult healthcare. It synthesises current knowledge and identifies gaps in HCT of ALwO. Drawing on successful practices and evidence-based interventions worldwide, the paper explores challenges, including disparities and barriers, while advocating for patient and family involvement. Additionally, it discusses barriers and perspectives within the Italian health care scenario. The need for specialised training for healthcare providers and the impact of transition on healthcare policies are also addressed. The conclusions underscore the significance of well-managed transitions. The SIO recognises that without proper support during this transition, ALwOs risk facing a gap in healthcare delivery, exacerbating their condition, and increasing the likelihood of complications. Addressing this gap requires concerted efforts to develop effective transition models, enhance healthcare provider awareness, and ensure equitable access to care for all individuals affected by obesity. The document concludes by outlining avenues for future research and improvement.


Subject(s)
Obesity , Transition to Adult Care , Humans , Adolescent , Transition to Adult Care/standards , Italy , Young Adult , Obesity/therapy , Delivery of Health Care/standards , Adult , Pediatric Obesity/therapy
4.
Curr Opin Clin Nutr Metab Care ; 26(1): 23-31, 2023 01 01.
Article in English | MEDLINE | ID: mdl-36485034

ABSTRACT

PURPOSE OF REVIEW: Early 2019, the Global Leadership Initiative on Malnutrition (GLIM) concept offered a clinically applicable and objective procedure for diagnosing malnutrition. This review summarizes 40 publications from August 2021 to August 2022 that applied the GLIM criteria in older populations from various clinical settings for criterion and predictive validation. RECENT FINDINGS: Criterion validity studies, by comparing the GLIM construct with various semi-gold standards such as SGA, PG-SGA, MNA-FF/SF and ESPEN criteria, indicate by sensitivity, specificity and agreement that GLIM performs at least as well as the other tools to capture malnutrition. One meta-analysis of 20 studies with various comparators reports high accuracy for distinguishing malnutrition. GLIM-malnutrition prevalence figures vary with screening tool. Predictive validity of GLIM for mortality, and other outcomes, is good in all settings reported. Sarcopenia and GLIM show some expected overlapping. SUMMARY: In populations more than 60 years old, the GLIM construct appears to have well acceptable criterion validity as well as predictive validity. The continuous implementation of the GLIM concept is justified.


Subject(s)
Malnutrition , Sarcopenia , Aged , Humans , Middle Aged , Feasibility Studies , Health Status , Leadership , Malnutrition/diagnosis , Nutrition Assessment , Sarcopenia/diagnosis
5.
Aging Clin Exp Res ; 35(7): 1487-1495, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37178430

ABSTRACT

BACKGROUND: Multidimensional Prognostic Index (MPI), calculated on cognitive, functional, nutritional, social, pharmacological and comorbidity domains, strongly correlates with mortality in older patients. Hip fractures are a major health problem and are associated with adverse outcomes in those affected by frailty. AIM: We aimed at evaluating whether MPI is a predictor of mortality and rehospitalization in hip fracture older patients. METHODS: We investigated the associations of MPI with all-cause 3- and 6-month mortality and rehospitalization in 1259 older patients admitted for hip fracture surgical treatment and managed by an orthogeriatric team [age 85 years (65-109); male gender: 22%]. RESULTS: Overall mortality was 11,4%, 17% and 23,5% at 3, 6 and 12 months from surgery (rehospitalizations: 15, 24,5 and 35,7%). MPI was associated (p < 0.001) with 3-, 6- and 12- month mortality and readmissions; Kaplan-Meier estimate for rehospitalization and survival according to MPI risk classes confirmed these results. In multiple regression analyses these associations were independent (p < 0.05) of mortality and rehospitalization-associated factors not included in the MPI, such as gender, age and post-surgical complications. Similar MPI predictive value was observed in patients undergoing endoprosthesis or other surgeries. ROC analysis confirmed that MPI was a predictor (p < 0.001) of both 3- and 6- month mortality and rehospitalization. CONCLUSIONS: In hip fracture older patients, MPI is a strong predictor of 3-, 6- and 12- months mortality and rehospitalization, independently of surgical treatment and post-surgical complications. Therefore, MPI should be considered a valid pre-surgical tool to identify patients with higher clinical risk of adverse outcomes.


Subject(s)
Hip Fractures , Patient Readmission , Humans , Male , Aged , Aged, 80 and over , Prognosis , Hip Fractures/surgery , Hip Fractures/epidemiology , Hospitalization , Comorbidity , Geriatric Assessment/methods , Risk Factors
6.
Aging Clin Exp Res ; 34(2): 409-418, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34255297

ABSTRACT

BACKGROUND: Frailty, demographic and clinical variables linked to incident diseases (e.g., dehydration, inflammation) contribute to poor outcomes in older patients acutely hospitalized. Their predictivity on short-, intermediate- and long-term mortality in a comprehensive model has been scarcely investigated. AIMS: To test the performance of a predictive tool considering frailty and inflammation as well as age, sex and impaired hydration status on 1-year mortality in acutely admitted older patients. METHODS: Retrospective observational study including 529 medical patients (age 84.6 ± 7.3 years). At hospital admission, frailty was assessed by the Multidimensional Prognostic Index (MPI). The Glasgow Prognostic Score (GPS) was used to grade systemic inflammation. Serum osmolarity was calculated to assess hydration. RESULTS: After adjusting for age, sex, GPS and osmolarity, the severe-risk MPI was a strong predictor for 1-year mortality (OR 4.133; 95% CI 2.273-7.516; p < 0.001). Age > 85 years, male sex, GPS-2 and serum osmolarity > 300 mOsm/L were independent predictors of mortality in the same multivariable model. The MPI alone showed a moderate discrimination power (AUC 0.678; 95% CI 0.628-0.729; p < 0.001) on 1-year mortality, which increased by 12.5% after the addition of the above predictors in the fully adjusted regression model (AUC 0.763; 95% CI 0.719-0.807; p < 0.001). The severe-risk MPI adjusted for the same factors was also an independent predictor of mortality after 60 and 180 days since hospital admission. DISCUSSION: Inflammation and impaired hydration are potentially modifiable risk factors for severe outcomes in older acutely hospitalized patients. A model combining GPS, age, gender, and plasma osmolarity improved the accuracy of MPI at admission in predicting long-term mortality.


Subject(s)
Frailty , Aged , Aged, 80 and over , Frailty/diagnosis , Geriatric Assessment , Hospitalization , Humans , Inflammation , Male , Prognosis , Prospective Studies
7.
Curr Opin Clin Nutr Metab Care ; 24(1): 4-9, 2021 01.
Article in English | MEDLINE | ID: mdl-33323713

ABSTRACT

PURPOSE OF REVIEW: In early 2019, the Global Leadership Initiative on Malnutrition (GLIM) concept was published advocating a two-step procedure, that is, screening followed by confirmation of the malnutrition diagnosis requiring a combination of phenotypic and etiologic criteria. This review summarizes 14 publications that have applied the GLIM criteria in older populations. RECENT FINDINGS: Four studies miss data on muscle mass. The mandatory screening appears missing in some studies. Two studies report that criterion validity is fair to good when compared with Subjective Global Assessment as semigold standard. Most studies report strong predictive validity when mortality is used as outcome. Not unexpectedly malnutrition relates strongly to sarcopenia as low muscle mass is a GLIM criterion. Overall, the lack of guidance on how to assess muscle mass and disease burden/inflammation in the original GLIM publication provides uncertainties on how to interpret the results. SUMMARY: Fourteen exclusively retrospective studies in older adult cohorts are summarized. In several cases, the data sets are imperfect or incomplete. Still, criterion and predictive validity for GLIM appears well acceptable when applied for older adults. Continuing global implementation efforts are justified. The GLIM consortium needs to provide guidance on assessment of muscle mass and disease burden/inflammation. Moreover, further prospective validation studies are needed to add knowledge for the future GLIM format updates.


Subject(s)
Malnutrition , Sarcopenia , Aged , Aged, 80 and over , Humans , Leadership , Malnutrition/diagnosis , Mass Screening , Retrospective Studies , Sarcopenia/diagnosis
8.
Curr Opin Clin Nutr Metab Care ; 24(1): 33-41, 2021 01.
Article in English | MEDLINE | ID: mdl-33323715

ABSTRACT

PURPOSE OF REVIEW: Tough plenty of literature investigated therapeutic options for body composition changes targeting elderly people, evidence concerning potential treatments of sarcopenic obesity as a unique condition is scarce. The aim of the present review was to summarize recent evidence regarding treatment of sarcopenic obesity in adult and older individuals. RECENT FINDINGS: Exercise-based interventions were effective in ameliorating lean mass or sarcopenia-related indices and reducing total adiposity. Importantly, in one study, modifications of body composition were obtained in the absence of significant changes in body mass index. The majority of studies relied on resistance training, and all provided with beneficial effects in body composition. Conversely, effects in terms of muscle strength and functional ability were heterogeneous. Electrical acupuncture and whole-body electromyostimulation associated with nutritional supplementation resulted to be novel effective strategies in inducing body composition changes. Nonetheless, findings from nutritional supplementations are not conclusive, leading to conflicting results on strength and functional outcomes. SUMMARY: Specific interventions could improve sarcopenic obesity, but overall significance is limited by scarcity of data and lack of uniformity in the definition of sarcopenic obesity itself. Further research should clarify optimal treatment options for sarcopenic obesity in age classes other than the geriatric population.


Subject(s)
Sarcopenia , Adiposity , Aged , Body Composition , Humans , Muscle Strength , Muscle, Skeletal , Obesity/complications , Obesity/therapy , Sarcopenia/therapy
9.
Support Care Cancer ; 29(11): 6721-6730, 2021 Nov.
Article in English | MEDLINE | ID: mdl-33973079

ABSTRACT

BACKGROUND: Increasing evidence indicates that nutritional status could influence the survival of cancer patients. This study aims to develop and validate a nomogram with nutrition-related parameters for predicting the overall survival of cancer patients. PATIENTS AND METHODS: A total of 8749 patients from the multicentre cohort study in China were included as the primary cohort to develop the nomogram, and 696 of these patients were recruited as a validation cohort. Patients' nutritional status were assessed using the PG-SGA. LASSO regression models and Cox regression analysis were used for factor selection and nomogram development. The nomogram was then evaluated for its effectiveness in discrimination, calibration, and clinical usefulness by the C-index, calibration curves, and decision curve analysis. Kaplan-Meier survival curves were used to compare the survival rate. RESULTS: Seven independent prognostic factors were identified and integrated into the nomogram. The C-index was 0.73 (95% CI, 0.72 to 0.74) and 0.77 (95% CI, 0.74 to 0.81) for the primary cohort and validation cohort, which were both higher than 0.59 (95% CI, 0.58 to 0.61) of the TNM staging system. DCA demonstrated that the nomogram was higher than the TNM staging system and the TNM staging system combined with PG-SGA. Significantly median overall survival differences were found by stratifying patients into different risk groups (score < 18.5 and ≥ 18.5) for each TNM category (all Ps < 0.001). CONCLUSION: Our study screened out seven independent prognostic factors and successfully generated an easy-to-use nomogram, and validated and shown a better predictive validity for the overall survival of cancer patients.


Subject(s)
Neoplasms , Nutritional Status , Cohort Studies , Humans , Neoplasm Staging , Nomograms , Prognosis
10.
Age Ageing ; 50(4): 1151-1158, 2021 06 28.
Article in English | MEDLINE | ID: mdl-33320928

ABSTRACT

BACKGROUND: impaired hydration is common in the older people, however studies of its effects on outcome in the acute setting are limited. OBJECTIVES: to assess (i) the prevalence of impaired hydration, (ii) its relationship with laboratory markers of altered hydration and with (iii) short- and long-term mortality. DESIGN: retrospective cohort study. SETTING: University Hospital-Internal Medicine Department. SUBJECTS: a total of 5,113 older patients consecutively acutely admitted from October 2015 to July 2016. METHODS: according to calculated serum osmolarity at admission hydration status was stratified in: low osmolarity (<275 mmol/L), euhydration (275-295 mmol/L), impending (296-300 mmol/L) and current dehydration (>300 mmol/L). Relationships with serum sodium, potassium, glucose, urea, estimated glomerular filtration rate (eGFR), haematocrit, urea/creatinine ratio (Urea/Cr) and urine specific gravity (USG) were determined. Charlson Comorbidity Index, Modified Early Warning Score, Glasgow Prognostic Score, Norton score and Nutritional Risk Screening-2002 were calculated. RESULTS: current and impending dehydration, euhydration and low-osmolarity were detected in 51.7, 17.1, 28.5 and 2.7% of the patients, respectively. Osmolarity correlated with urea (r = 0.846). Associations with serum sodium, creatinine, eGFR and urea/Cr were low but significant, being negligible that with USG and haematocrit. Serum sodium and urea increased in the transition from low- to high-osmolarity (P < 0.001 in all pairwise comparisons). In multivariate modelling current dehydration, functional dependence, clinical instability and high nutritional risk were associated (P < 0.001) with reduced short- and long-term survival. CONCLUSIONS: impaired hydration is common in older people acutely admitted to medical care and is associated with poor outcome. Early assessment of calculated serum osmolarity is mandatory to target dehydration and hypoosmolar disorders.


Subject(s)
Dehydration , Hospitalization , Aged , Humans , Osmolar Concentration , Prevalence , Retrospective Studies
11.
BMC Geriatr ; 21(1): 687, 2021 12 10.
Article in English | MEDLINE | ID: mdl-34893024

ABSTRACT

BACKGROUND: This study was sought to report the prevalence of malnutrition in elderly patients with cancer. Validate the predictive value of the nutritional assessment tool (Patient-Generated Subjective Global Assessment Short Form, PG-SGA SF) for clinical outcomes and assist the therapeutic decision. METHODS: This is a secondary analysis of a multicentric, observational cohort study. Elderly patients with cancer older than 65 years were enrolled after the first admission. Nutritional status was identified using the PG-SGA SF. RESULTS: Of the 2724 elderly patients included in the analysis, 65.27% of patients were male (n = 1778); the mean age was 71.00 ± 5.36 years. 31.5% of patients were considered malnourished according to PG-SGA SF. In multivariate analysis, malnutrition(PG-SGA SF > 5) was significantly associated with worse OS (HR: 1.47,95%CI:1.29-1.68), affects the quality of life, and was related to more frequent nutrition impact symptoms. During a median follow-up of 4.5 years, 1176 death occurred. The mortality risk was 41.10% for malnutrition during the first 12 months and led to a rate of 323.98 events per-1000-patient-years. All nutritional assessment tools were correlated with each other (PG-SGA SF vs. PG-SGA: r = 0.98; PG-SGA SF vs. GLIM[Global Leadership Initiative on Malnutrition]: r = 0.48, all P < 0.05). PG-SGA SF and PG-SGA performed similarly to predict mortality but better than GLIM. PG-SGA SF improves the predictive ability of the TNM classification system for mortality in elderly patients with cancer, including distinguishing patients' prognoses and directing immunotherapy. CONCLUSIONS: The nutritional status as measured by PG-SGA SF which is a prognostic factor for OS in elderly cancer patients and could improve the prognostic model of TNM.


Subject(s)
Malnutrition , Neoplasms , Aged , Humans , Male , Malnutrition/diagnosis , Malnutrition/epidemiology , Neoplasms/complications , Neoplasms/diagnosis , Neoplasms/epidemiology , Nutrition Assessment , Nutritional Status , Quality of Life
12.
Rev Endocr Metab Disord ; 21(3): 307-313, 2020 09.
Article in English | MEDLINE | ID: mdl-32766943

ABSTRACT

A paradoxical double challenge has emerged in the last decades with respect to nutrition and nutrition-related clinical conditions. Hunger-related undernutrition continues to represent an unacceptable burden, although its prevalence has been encouragingly reduced worldwide. On the other hand, the prevalence of overweight and obesity, defined as fat excess accumulation with negative impact on individual health, has dramatically increased due to increasingly pervasive obesogenic lifestyle changes. Undernutrition and obesity may coexist in world regions, Countries and even smaller communities and households, being referred to as double burden of malnutrition. It is however important to point out that fat accumulation and obesity may also induce additional nutritional derangements in affected individuals, both directly through metabolic and body composition changes and indirectly through acute and chronic diseases with negative impact on nutritional status. In the current narrative review, associations between fat accumulation in obesity and malnutrition features as well as their known causes will be reviewed and summarized. These include risk of loss of skeletal muscle mass and function (sarcopenia) that may allow for malnutrition diagnosis also in overweight and obese individuals, thereby introducing a new clinically relevant perspective to the obesity-related double burden of malnutrition concept.


Subject(s)
Malnutrition/complications , Obesity/etiology , Adipose Tissue/metabolism , Feeding Behavior/physiology , Food Preferences/physiology , Humans , Life Style , Malnutrition/epidemiology , Malnutrition/metabolism , Nutritional Status/physiology , Obesity/epidemiology , Obesity/metabolism , Sarcopenia/epidemiology , Sarcopenia/etiology , Sarcopenia/metabolism
14.
Int J Mol Sci ; 20(3)2019 Jan 24.
Article in English | MEDLINE | ID: mdl-30682769

ABSTRACT

Unacylated ghrelin (UnGhr) exerts several beneficial actions on vascular function. The aim of this study was to assess the effects of UnGhr on high-fat induced endothelial dysfunction and its underlying mechanisms. Thoracic aortas from transgenic mice, which were overexpressing UnGhr and being control fed either a standard control diet (CD) or a high-fat diet (HFD) for 16 weeks, were harvested and used for the assessment of vascular reactivity, endothelial nitric oxide synthase (eNOS) expression and activity, thiobarbituric acid reactive substances (TBARS) and glutathione levels, and aortic lipid accumulation by Oil Red O staining. Relaxations due to acetylcholine and to DEA-NONOate were reduced (p < 0.05) in the HFD control aortas compared to vessels from the CD animals. Overexpression of UnGhr prevented HFD-induced vascular dysfunction, while eNOS expression and activity were similar in all vessels. HFD-induced vascular oxidative stress was demonstrated by increased (p < 0.05) aortic TBARS and glutathione in wild type (Wt) mice; however, this was not seen in UnGhr mice. Moreover, increased (p < 0.05) HFD-induced lipid accumulation in vessels from Wt mice was prevented by UnGhr overexpression. In conclusion, chronic UnGhr overexpression results in improved vascular function and reduced plaque formation through decreased vascular oxidative stress, without affecting the eNOS pathway. This research may provide new insight into the mechanisms underlying the beneficial effects of UnGhr on the vascular dysfunction associated with obesity and the metabolic syndrome.


Subject(s)
Atherosclerosis/metabolism , Endothelium, Vascular/metabolism , Ghrelin/genetics , Animals , Aorta/metabolism , Atherosclerosis/etiology , Atherosclerosis/genetics , Diet, High-Fat/adverse effects , Ghrelin/metabolism , Lipid Metabolism , Male , Mice , Nitric Oxide Synthase Type III , Oxidative Stress , Up-Regulation
15.
Eat Weight Disord ; 24(6): 997-1013, 2019 Dec.
Article in English | MEDLINE | ID: mdl-30353455

ABSTRACT

Ghrelin is a gastric hormone circulating in acylated (AG) and unacylated (UnAG) forms. This narrative review aims at presenting current emerging knowledge on the impact of ghrelin forms on energy balance and metabolism. AG represents ~ 10% of total plasma ghrelin, has an appetite-stimulating effect and is the only form for which a receptor has been identified. Moreover, other metabolic AG-induced effects have been reported, including the modulation of glucose homeostasis with stimulation of liver gluconeogenesis, the increase of fat mass and the improvement of skeletal muscle mitochondrial function. On the other hand, UnAG has no orexigenic effects, however recent reports have shown that it is directly involved in the modulation of skeletal muscle energy metabolism by improving a cluster of interlinked functions including mitochondrial redox activities, tissue inflammation and insulin signalling and action. These findings are in agreement with human studies which show that UnAG circulating levels are positively associated with insulin sensitivity both in metabolic syndrome patients and in a large cohort from the general population. Moreover, ghrelin acylation is regulated by a nutrient sensor mechanism, specifically set on fatty acids availability. These recent findings consistently point towards a novel independent role of UnAG as a regulator of muscle metabolic pathways maintaining energy status and tissue anabolism. While a specific receptor for UnAG still needs to be identified, recent evidence strongly supports the hypothesis that the modulation of ghrelin-related molecular pathways, including those involved in its acylation, may be a potential novel target in the treatment of metabolic derangements in disease states characterized by metabolic and nutritional complications.Level of evidence Level V, narrative review.


Subject(s)
Adipose Tissue/metabolism , Appetite/physiology , Energy Metabolism/physiology , Ghrelin/physiology , Gluconeogenesis/physiology , Glucose/metabolism , Liver/metabolism , Muscle, Skeletal/metabolism , Acylation , Energy Intake/physiology , Ghrelin/metabolism , Homeostasis , Humans , Insulin Resistance , Mitochondria, Muscle/metabolism
16.
FASEB J ; 31(12): 5159-5171, 2017 12.
Article in English | MEDLINE | ID: mdl-28778977

ABSTRACT

Unacylated ghrelin (UnAG) may lower skeletal muscle oxidative stress, inflammation, and insulin resistance in lean and obese rodents. UnAG-induced autophagy activation may contribute to these effects, likely involving removal of dysfunctional mitochondria (mitophagy) and redox state maintenance. In chronic kidney disease (CKD) oxidative stress, inflammation and insulin resistance may negatively influence patient outcome by worsening nutritional state through muscle mass loss. Here we show in a 5/6 nephrectomy (Nx) CKD rat model that 4 d s.c. UnAG administration (200 µg twice a day) normalizes CKD-induced loss of gastrocnemius muscle mass and a cluster of high tissue mitochondrial reactive oxygen species generation, high proinflammatory cytokines, and low insulin signaling activation. Consistent with these results, human uremic serum enhanced mitochondrial reactive oxygen species generation and lowered insulin signaling activation in C2C12 myotubes while concomitant UnAG incubation completely prevented these effects. Importantly, UnAG enhanced muscle mitophagy in vivo and silencing RNA-mediated autophagy protein 5 silencing blocked UnAG activities in myotubes. UnAG therefore normalizes CKD-induced skeletal muscle oxidative stress, inflammation, and low insulin signaling as well as muscle loss. UnAG effects are mediated by autophagy activation at the mitochondrial level. UnAG administration and mitophagy activation are novel potential therapeutic strategies for skeletal muscle metabolic abnormalities and their negative clinical impact in CKD.-Gortan Cappellari, G., Semolic, A., Ruozi, G., Vinci, P., Guarnieri, G., Bortolotti, F., Barbetta, D., Zanetti, M., Giacca, M., Barazzoni, R. Unacylated ghrelin normalizes skeletal muscle oxidative stress and prevents muscle catabolism by enhancing tissue mitophagy in experimental chronic kidney disease.


Subject(s)
Ghrelin/therapeutic use , Muscle, Skeletal/drug effects , Muscle, Skeletal/metabolism , Oxidative Stress/drug effects , Renal Insufficiency, Chronic/drug therapy , Renal Insufficiency, Chronic/metabolism , Animals , Autophagy/drug effects , Gene Silencing , Insulin/metabolism , Male , Mitochondria/drug effects , Mitochondria/metabolism , Mitophagy/drug effects , Muscle Fibers, Skeletal/drug effects , Muscle Fibers, Skeletal/metabolism , Rats , Rats, Wistar , Reactive Oxygen Species/metabolism , Signal Transduction/drug effects
17.
Int J Mol Sci ; 19(1)2018 Jan 11.
Article in English | MEDLINE | ID: mdl-29324650

ABSTRACT

Elderly and patients affected by chronic diseases face a high risk of muscle loss and impaired physical function. Omega 3 fatty acids (FA) attenuate inflammation and age-associated muscle loss, prevent systemic insulin resistance and improve plasma lipids, potentially impacting on sarcopenia. This paper aims to review recent randomized clinical studies assessing the effects a chronic omega 3 FA supplementation on inflammatory and metabolic profile during conditions characterized by sarcopenia (aging, insulin resistance, type 2 diabetes, chronic renal failure). A comprehensive search of three online databases was performed to identify eligible trials published between 2012 and 2017. A total of 36 studies met inclusion criteria. Omega 3 FA yielded mixed results on plasma triglycerides in the elderly and no effects in renal patients. No changes in systemic insulin resistance were observed. Inflammation markers did not benefit from omega 3 FA in insulin resistant and in renal subjects while decreasing in obese and elderly. Muscle related parameters improved in elderly and in renal patients. In conclusion, in aging- and in chronic disease-associated sarcopenia omega 3 FA are promising independently of associated anabolic stimuli or of anti-inflammatory effects. The evidence for improved glucose metabolism in insulin resistant and in chronic inflammatory states is less solid.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Fatty Acids, Omega-3/therapeutic use , Insulin Resistance , Sarcopenia/drug therapy , Anti-Inflammatory Agents/administration & dosage , Fatty Acids, Omega-3/administration & dosage , Humans , Lipid Metabolism , Oxidative Stress , Randomized Controlled Trials as Topic , Sarcopenia/metabolism
18.
Eat Weight Disord ; 23(2): 149-157, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29397563

ABSTRACT

Obesity is a major health risk factor, and obesity-induced morbidity and complications account for huge costs for affected individuals, families, healthcare systems, and society at large. In particular, obesity is strongly associated with the development of insulin resistance, which in turn plays a key role in the pathogenesis of obesity-associated cardiometabolic complications, including metabolic syndrome components, type 2 diabetes, and cardiovascular diseases. Insulin sensitive tissues, including adipose tissue, skeletal muscle, and liver, are profoundly affected by obesity both at biomolecular and functional levels. Altered adipose organ function may play a fundamental pathogenetic role once fat accumulation has ensued. Modulation of insulin sensitivity appears to be, at least in part, related to changes in redox balance and oxidative stress as well as inflammation, with a relevant underlying role for mitochondrial dysfunction that may exacerbate these alterations. Nutrients and substrates as well as systems involved in host-nutrient interactions, including gut microbiota, have been also identified as modulators of metabolic pathways controlling insulin action. This review aims at providing an overview of these concepts and their potential inter-relationships in the development of insulin resistance, with particular regard to changes in adipose organ and skeletal muscle.


Subject(s)
Diabetes Mellitus, Type 2/metabolism , Insulin Resistance/physiology , Obesity/metabolism , Oxidative Stress/physiology , Humans , Inflammation/metabolism
19.
J Ren Nutr ; 27(6): 474-477, 2017 11.
Article in English | MEDLINE | ID: mdl-29056169

ABSTRACT

In patients with chronic kidney disease (CKD), malnutrition with loss of skeletal muscle mass has a negative impact on morbidity and mortality. Emerging evidence indicates that a cluster of oxidative stress, inflammation, and insulin resistance directly contributes to skeletal muscle catabolism by favoring protein breakdown over synthesis. Ghrelin is a gastric hormone discovered and initially studied in its acylated orexigenic form. More recently, a role of unacylated ghrelin (UnAG) has been described to reduce skeletal muscle mitochondrial reactive oxygen species generation, inflammation, and insulin resistance both in experimental models and in clinical studies. UnAG administration could therefore represent a potential comprehensive therapeutic approach for CKD-related metabolic and nutritional complications. Studies of UnAG administration in experimental and clinical CKD are needed to test the hypothesis that UnAG may chronically improve nutritional status and outcome in CKD patients.


Subject(s)
Ghrelin/pharmacology , Muscular Diseases/drug therapy , Renal Insufficiency, Chronic/drug therapy , Humans , Inflammation/drug therapy , Malnutrition/complications , Malnutrition/drug therapy , Muscle, Skeletal/drug effects , Muscle, Skeletal/metabolism , Muscular Diseases/complications , Reactive Oxygen Species/metabolism , Renal Insufficiency, Chronic/complications
20.
JPEN J Parenter Enteral Nutr ; 48(5): 546-553, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38734876

ABSTRACT

Obesity is a challenging chronic disease process that continues to affect a large percentage of the population at large. With the advent of new therapeutic options and interventions and a deeper scientific understanding of obesity as a complex illness, there is hope in curtailing this evolving pandemic. In this article, we present key medical information to engage and empower nutrition-focused providers to manage obesity and its nutrition complications. The topics summarized here were presented during the 2023 American Society for Parenteral and Enteral Nutrition Preconference Physician Course and include pathophysiology and hormonal regulation of obesity, multidisciplinary care planning and nutrition risk stratification of patients, and common approaches to treatment, including lifestyle modifications, antiobesity medications, and procedures from the perspective of the nutrition specialist.


Subject(s)
Obesity , Humans , Obesity/therapy , Anti-Obesity Agents/therapeutic use , Physicians , Parenteral Nutrition/methods , Life Style , Enteral Nutrition/methods , Nutritionists
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