Detecting sarcopenia in obesity: emerging new approaches.

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.

Multidimensional prognostic index predicts short- and long-term mortality and rehospitalizations in older patients with hip fracture.

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.

Double burden of malnutrition in persons with obesity.

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.

Unacylated Ghrelin Improves Vascular Dysfunction and Attenuates Atherosclerosis during High-Fat Diet Consumption in Rodents.

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.

Ghrelin forms in the modulation of energy balance and metabolism.

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.

Unacylated ghrelin normalizes skeletal muscle oxidative stress and prevents muscle catabolism by enhancing tissue mitophagy in experimental chronic kidney disease.

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.

Update on the Impact of Omega 3 Fatty Acids on Inflammation, Insulin Resistance and Sarcopenia: A Review.

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.

Insulin resistance in obesity: an overview of fundamental alterations.

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.

Unacylated Ghrelin: A Novel Regulator of Muscle Intermediate Metabolism With Potential Beneficial Effects in Chronic Kidney Disease.

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.

Defining and diagnosing sarcopenia: Is the glass now half full?

Low muscle mass and function exert a substantial negative impact on quality of life, health and ultimately survival, but their definition, identification and combination to define sarcopenia have suffered from lack of universal consensus. Methodological issues have also contributed to incomplete agreement, as different approaches, techniques and potential surrogate measures inevitably lead to partly different conclusions. As a consequence: 1) awareness of sarcopenia and implementation of diagnostic procedures in clinical practice have been limited; 2) patient identification and evaluation of therapeutic strategies is largely incomplete. Significant progress has however recently occurred after major diagnostic algorithms have been developed, with common features and promising perspectives for growing consensus. At the same time, the need for further refinement of the sarcopenia concept has emerged, to address its increasingly recognized clinical heterogeneity. This includes potential differential underlying mechanisms and clinical features for age- and disease-driven sarcopenia, and the emerging challenge of sarcopenia in persons with obesity. Here, we will review existing algorithms to diagnose sarcopenia, and major open methodological issues to assess skeletal muscle mass and function under different clinical conditions, in order to highlight similarities and differences. Potential for consensus on sarcopenia diagnosis as well as emerging new challenges will be discussed.

n-3 PUFA-Enriched Diet Preserves Skeletal Muscle Mitochondrial Function and Redox State and Prevents Muscle Mass Loss in Mice with Chronic Heart Failure.

Rationale and Methods: Skeletal muscle derangements, potentially including mitochondrial dysfunction with altered mitochondrial dynamics and high reactive oxygen species (ROS) generation, may lead to protein catabolism and muscle wasting, resulting in low exercise capacity and reduced survival in chronic heart failure (CHF). We hypothesized that 8-week n-3-PUFA isocaloric partial dietary replacement (Fat = 5.5% total cal; EPA + DHA = 27% total fat) normalizes gastrocnemius muscle (GM) mitochondrial dynamics regulators, mitochondrial and tissue pro-oxidative changes, and catabolic derangements, resulting in preserved GM mass in rodent CHF [Myocardial infarction (MI)-induced CHF by coronary artery ligation, left-ventricular ejection fraction <50%]. Results: Compared to control animals (Sham), CHF had a higher GM mitochondrial fission-fusion protein ratio, with low ATP and high ROS production, pro-inflammatory changes, and low insulin signalling. n-3-PUFA normalized all mitochondrial derangements and the pro-oxidative state (oxidized to total glutathione ratio), associated with normalized GM cytokine profile, and enhanced muscle-anabolic insulin signalling and prevention of CHF-induced GM weight loss (all p < 0.05 vs. CHF and p = NS vs. S). Conclusions:n-3-PUFA isocaloric partial dietary replacement for 8 weeks normalizes CHF-induced derangements of muscle mitochondrial dynamics regulators, ROS production and function. n-3-PUFA mitochondrial effects result in preserved skeletal muscle mass, with potential to improve major patient outcomes in clinical settings.

Sarcopenic obesity in free-living older adults detected by the ESPEN-EASO consensus diagnostic algorithm: Validation in an Italian cohort and predictive value of insulin resistance and altered plasma ghrelin profile.

Aging and obesity are synergistic sarcopenia risk factors (RF). Their association in sarcopenic obesity (SO) enhances morbidity and mortality, but consensus on SO diagnostic criteria is limited. ESPEN and EASO issued a consensus algorithm for SO screening (obesity and clinical SO suspicion) and diagnosis [low muscle strength by hand-grip (HGS) and low muscle mass by BIA], and we investigated its implementation in older adults (>65-years), as well as SO-associated metabolic RF [insulin resistance (IR: HOMA) and plasma acylated (AG) and unacylated (UnAG) ghrelin, with predictive value also assessed from 5-year-prior observations]. Older adults with obesity from the Italian MoMa study on metabolic syndrome in primary care (n = 76) were studied. 7 of 61 individuals with positive screening had SO (SO+; 9 % of cohort). No individuals with negative screening had SO. SO+ had higher IR, AG and plasma AG/UnAG ratio (p < 0.05 vs negative screening and SO-), and both IR and ghrelin profile predicted 5-year SO risk independent of age, sex and BMI. The current results provide the first ESPEN-EASO algorithm-based investigation of SO in free-living older adults, with 9 % prevalence in those with obesity and 100 % algorithm sensitivity, and they support IR and plasma ghrelin profile as SO risk factors in this setting.

Sarcopenic obesity research perspectives outlined by the sarcopenic obesity global leadership initiative (SOGLI) - Proceedings from the SOGLI consortium meeting in rome November 2022.

The European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO) launched the Sarcopenic Obesity Global Leadership Initiative (SOGLI) to reach expert consensus on a definition and diagnostic criteria for Sarcopenic Obesity (SO). The present paper describes the proceeding of the Sarcopenic Obesity Global Leadership Initiative (SOGLI) meeting that was held on November 25th and 26th, 2022 in Rome, Italy. This consortium involved the participation of 50 researchers from different geographic regions and countries. The document outlines an agenda advocated by the SOGLI expert panel regarding the pathophysiology, screening, diagnosis, staging and treatment of SO that needs to be prioritized for future research in the field.

Ghrelin and muscle metabolism in chronic uremia.

Patients with chronic kidney disease (CKD) are prone to nutritional complications with negative prognostic impact. In particular, protein-energy wasting is a major CKD-associated clinical burden, and emerging evidence indicates that clustered metabolic alterations, including inflammation, oxidative stress, and insulin resistance, contribute to loss of skeletal muscle mass. Ghrelin is a gastric hormone discovered in its acylated form and extensively studied for its appetite-stimulating effect. Further studies have shown that ghrelin may positively modulate systemic inflammation and insulin action. In addition, a role of ghrelin in the regulation of redox state has been described in vitro. Ghrelin treatment could therefore represent a potential comprehensive therapeutic approach for CKD-related metabolic and nutritional complications, and evidence supporting this hypothesis has emerged in clinical and experimental CKD. Clinical trials of ghrelin administration are needed to test the hypothesis that ghrelin may chronically improve nutritional status and outcome in CKD patients.

Postoperative Dehydration Is Associated with Frailty and Decreased Survival in Older Patients with Hip Fracture.

BACKGROUND: Hyperosmolar dehydration (HD) is a risk factor for severe complications in hip fracture in older patients. However, evidence for recommending screening of dehydration is insufficient and its relation with frailty and mortality is unclear. We tested the hypothesis that postoperative HD is associated with frailty and increased mortality. METHODS: We recruited 625 older (>65 years) patients surgically treated for hip fracture and co-managed by an orthogeriatric team over one year in 2017. Pre- and postoperative HD (serum osmolarity > 300 mmol/L) was diagnosed. Frailty and associated mortality risk were assessed by the Multidimensional Prognostic Index (MPI). RESULTS: The prevalence of preoperative HD was 20.4%. Compared with no-HD, MPI was similar in HD patients despite higher (p < 0.05) prevalence of polypharmacy, arterial hypertension, diabetes, chronic kidney disease and heart failure. After surgery the incidence of HD decreased to 16.5%, but increased (p = 0.003) in the MPI high-risk subgroup. Postoperative HD was associated with more complications and was an independent determinant of adjusted hospital length of stay (LOS) and of 60- to 365-days mortality. CONCLUSIONS: Older frail patients with hip fracture are prone to developing postoperative HD, which independently predicts prolonged hospital LOS and mortality. Systematically screening older patients for frailty and dehydration is advisable to customize hydration management in high-risk individuals.

Sarcopenic obesity: What about in the cancer setting?

Growing evidence suggests that changes in muscle mass and function may further contribute to health risk assessment in individuals who are obese. As numbers for both obese and aged population subgroups are increasing worldwide, sarcopenic obesity is emerging as a relevant factor associated with higher risk for adverse events and outcomes in several clinical settings, including cancer. Recent reports showing that prevalence of sarcopenic obesity may involve up to one-third of patients with cancer despite body mass index strongly support the need for its evaluation in oncological clinical practice. In fact, in several cancer types, sarcopenic obesity is associated with poorer outcomes that include metabolic and surgical complications, longer hospitalization, physical disability, and shorter survival. Importantly, sarcopenic obesity may also have an effect on chemotherapy, as it may induce a higher risk for dose-limiting-toxicity. The aim of this review was to present an updated overview on the definition, effects, mechanisms, and clinical relevance of sarcopenia in this setting.

n-3 PUFA dietary lipid replacement normalizes muscle mitochondrial function and oxidative stress through enhanced tissue mitophagy and protects from muscle wasting in experimental kidney disease.

INTRODUCTION AND METHODS: Skeletal muscle mitochondrial dysfunction may cause tissue oxidative stress and consequent catabolism in chronic kidney disease (CKD), contributing to patient mortality. We investigated in 5/6-nephrectomized (Nx) rats the impact of n3-polyunsaturated fatty-acids (n3-PUFA) isocaloric partial dietary replacement on gastrocnemius muscle (Gm) mitochondrial master-regulators, ATP production, ROS generation and related muscle-catabolic derangements. RESULTS: Nx had low Gm mitochondrial nuclear respiratory factor-2 and peroxisome proliferator-activated receptor gamma coactivator-1alpha, low ATP production and higher mitochondrial fission-fusion protein ratio with ROS overproduction. n3-PUFA normalized all mitochondrial derangements and pro-oxidative tissue redox state (oxydized to total glutathione ratio). n3-PUFA also normalized Nx-induced muscle-catabolic proinflammatory cytokines, insulin resistance and low muscle weight. Human uremic serum reproduced mitochondrial derangements in C2C12 myotubes, while n3-PUFA coincubation prevented all effects. n3-PUFA also enhanced muscle mitophagy in-vivo and siRNA-mediated autophagy inhibition selectively blocked n3-PUFA-induced normalization of C2C12 mitochondrial ROS production. CONCLUSIONS: In conclusion, dietary n3-PUFA normalize mitochondrial master-regulators, ATP production and dynamics in experimental CKD. These effects occur directly in muscle cells and they normalize ROS production through enhanced mitophagy. Dietary n3-PUFA mitochondrial effects result in normalized catabolic derangements and protection from muscle wasting, with potential positive impact on patient survival.

Hemodialysis induces p66(shc) gene expression in nondiabetic humans: correlations with oxidative stress and systemic inflammation.

OBJECTIVE: Oxidative stress and inflammation characterize hemodialysis (HD) and are associated with malnutrition, cardiovascular disease, and poor clinical outcome. p66(shc) stimulates oxidative stress and atherogenesis. The objective of the present study was to assess p66(shc) expression levels in HD and their associations with inflammatory and oxidative stress markers. DESIGN: p66(shc) messenger ribonucleic acid (mRNA) was compared with systemic oxidative stress and inflammation markers in control subjects and patients on HD before and after a single HD session in a cross-sectional analysis. SETTING: Outpatient hemodialysis unit. PATIENTS: The study included stable HD patients (n = 21, men/women: 18/3) who were on HD 3 times per week for a minimum of 8 weeks; age-matched control subjects (n = 22, men/women:17/5). MAIN OUTCOME MEASURE: mRNA levels of p66(shc), tumor necrosis factor α (TNF-α), and pentraxin 3 (PTX3), p66(shc) protein levels in white blood cells, lipid peroxidation (in the form of plasma thiobarbituric acid-reactive substance [TBARS]) and serum C-reactive protein. RESULTS: In patients on dialysis, of the p66(shc), TNF-α, and PTX3 mRNAs, p66(shc) protein levels were higher (P < .05) than in control subjects, as well as plasma TBARS and C-reactive protein (P < .05). p66(shc) mRNA directly correlated with TBARS (r = 0.69, P = .0005) and with TNF-α mRNA (r = 0.63, P = .003). These associations were confirmed in the whole study population (TBARS: r = 0.541, P = .0003; TNF-α: r = 0.581, P < .0001), whereas in the control group only the positive association between p66(shc) and TNF-α was detected. TNF-α was directly correlated with PTX3 both in HD patients (r = 0.72, P = .0005) and in the whole study group (r = 0.678, P < .0001). The dialysis session affected neither p66(shc) and TNF-α mRNA nor p66(shc) protein expression, whereas it further increased (P = .002) PTX3 mRNA. As compared with predialysis levels, TBARS were reduced (P < .05) after dialysis. In these conditions, p66(shc) remained directly correlated with TNF-α (r = 0.901, P < .0001). CONCLUSIONS: Increased p66(shc) gene expression correlates with TNF-α mRNA and with levels of markers of oxidative stress in HD. We suggest a novel link between HD-associated inflammation and p66(shc) gene expression contributing to systemic oxidative stress.

Higher unacylated ghrelin and insulin sensitivity following dietary restriction and weight loss in obese humans.

BACKGROUND & AIMS: Unacylated ghrelin (UnAG) modulates insulin sensitivity. Low plasma UnAG occurs in obesity and potentially contributes to obesity-associated insulin resistance. We hypothesized that improvements in insulin sensitivity in obese people induced by moderate caloric restriction (CR) may be paralleled and at least in part explained by concurrent increases in UnAG levels. METHODS: 20 general community obese people were randomly assigned to 16-week CR (n = 11) or control diet (n = 9). We investigated the impact of CR on the interaction between insulin sensitivity changes [area under the curve (AUCg) of glucose infusion to maintain euglycemia during hyperinsulinemic-euglycemic clamp] and plasma total (TotalG), acylated (AG) and Unacylated ghrelin (UnAG). Plasma pro-inflammatory tumor necrosis factor alpha (TNFα) and anti-inflammatory interleukin-10 (IL-10) were also measured since changes in inflammation may contribute to UnAG activities. RESULTS: CR reduced BMI and increased insulin sensitivity (p < 0.05). TotalG and UnAG but not AG increased in CR but not in Control (p < 0.05). Il-10 and IL-10/TNFα ratio also increased in CR (p < 0.05). Changes in UnAG were positively associated with changes in AUCg in all subjects (n = 20; p < 0.01) also after adjustment for treatment and changes in BMI and cytokines. CONCLUSIONS: Caloric restriction modifies circulating ghrelin profile with selective increase in unacylated hormone in obese individuals. The current study supports the hypothesis that higher unacylated ghrelin contributes to improvements in insulin sensitivity following diet-induced weight loss in human obesity.

The Impact of Protein Supplementation Targeted at Improving Muscle Mass on Strength in Cancer Patients: A Scoping Review.

Deterioration of muscle strength during cancer results in functional limitation, poor quality of life and reduced survival. The indirect effects on muscle strength of nutritional interventions based on protein and amino acid derivatives targeted at improving muscle mass are poorly documented. A scoping review was performed to examine the available evidence on the effects of proteins, amino acids and their derivatives on muscle strength in adult cancer patients. Pubmed and Scopus databases were searched to identify research articles published in the last 10 years. Fourteen studies met the inclusion criteria, showing that changes in muscle strength following protein or amino acid supplementation are generally concordant with those in muscle mass in cancer patients. Administration of both energy and proteins in the presence of reduced oral intakes results in more robust effects on both muscle strength and mass. It is not clear whether this is due to the correction of the energy deficit or to an interaction between proteins and other macronutrients. The optimal mixture, type, and dose of amino acid/protein supplementation alone or in combination with other anabolic strategies should be determined to provide the best nutritional approach in cancer.