High-protein diet with excess leucine prevents inactivity-induced insulin resistance in women.

Background And Aims: Muscle inactivity leads to muscle atrophy and insulin resistance. The branched-chain amino acid (BCAA) leucine interacts with the insulin signaling pathway to modulate glucose metabolism. We have tested the ability of a high-protein BCAA-enriched diet to prevent insulin resistance during long-term bed rest (BR).

Lipoprotein(a) as a Risk Factor for Cardiovascular Diseases: Pathophysiology and Treatment Perspectives.

Cardiovascular disease (CVD) is still a leading cause of morbidity and mortality, despite all the progress achieved as regards to both prevention and treatment. Having high levels of lipoprotein(a) [Lp(a)] is a risk factor for cardiovascular disease that operates independently. It can increase the risk of developing cardiovascular disease even when LDL cholesterol (LDL-C) levels are within the recommended range, which is referred to as residual cardiovascular risk.

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].

[Identifying possible homozygous familial hypercholesterolemia patients: an Italian experts' opinion].

Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disease characterized by high plasma levels of low-density lipoprotein cholesterol (LDL-C) and massive risk of premature atheromasia and cardiovascular events. HoFH is caused by mutations in several genes, such as LDLR, APOB, PCSK9 and LDLRAP1. If untreated, the average age of death is 18 years old, but fatalities within the first 5 years of age have been recorded.

Mechanism of action and therapeutic use of bempedoic acid in atherosclerosis and metabolic syndrome.

Bempedoic acid is a new cholesterol-lowering drug, which has recently received US FDA and EMA approval. This drug targets lipid and glucose metabolism as well as inflammation downregulation of ATP-citrate lyase and upregulation of AMP-activated protein kinase (AMPK). The primary effect is the reduction of cholesterol synthesis in the liver and its administration is generally not associated to unwanted muscle effects.

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.

Skeletal Muscle in Hypoxia and Inflammation: Insights on the COVID-19 Pandemic.

SARS-CoV-2 infection is often associated with severe inflammation, oxidative stress, hypoxia and impaired physical activity. These factors all together contribute to muscle wasting and fatigue. In addition, there is evidence of a direct SARS-CoV-2 viral infiltration into skeletal muscle.

Ruling Out Coronavirus Disease 2019 in Patients with Pneumonia: The Role of Blood Cell Count and Lung Ultrasound.

Coronavirus disease 2019 (COVID-19) is characterized by a distinctive blood leucocyte pattern and B-lines on lung ultrasound (LUS) as marker of alveolar-interstitial syndrome. We aimed to evaluate the accuracy of blood leucocyte count alone or in combination with LUS for COVID-19 diagnosis. We retrospectively enrolled consecutive patients diagnosed with community acquired pneumonia (CAP) at hospital admission to derive and validate cutoff values for blood cell count that could be predictive of COVID-19 before confirmation by the nucleic acid amplification test (NAAT).

Central adiposity markers, plasma lipid profile and cardiometabolic risk prediction in overweight-obese individuals.

Background: Waist circumference (WC) is the currently recommended marker of central fat for cardiometabolic risk screening. Alternative surrogate markers have been recently proposed to better reflect the metabolic impact of central fat accumulation per se, based on WC normalization by height (Weight-to-Height Ratio - WtoH; Body Roundness Index - BRI) or body mass index (BMI) without (A Body Shape Index - ABSI) or with inclusion of plasma triglyceride and HDL-cholesterol concentrations (Visceral Adiposity Index - VAI).

Methods: We investigated associations between WtoH, BRI, ABSI or VAI and insulin resistance (HOMA-index) or metabolic syndrome (MetS) in a general population cohort from the North-East Italy Mo.

Acylated ghrelin treatment normalizes skeletal muscle mitochondrial oxidative capacity and AKT phosphorylation in rat chronic heart failure.

Background: Chronic heart failure (CHF) is associated with skeletal muscle abnormalities contributing to exercise intolerance, muscle loss, and negative impact on patient prognosis. A primary role has been proposed for mitochondrial dysfunction, which may be induced by systemic and tissue inflammation and further contribute to low insulin signalling. The acylated form of the gastric hormone ghrelin (AG) may improve mitochondrial oxidative capacity and insulin signalling in both healthy and diseased rodent models.

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.

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.

Unacylated Ghrelin Reduces Skeletal Muscle Reactive Oxygen Species Generation and Inflammation and Prevents High-Fat Diet-Induced Hyperglycemia and Whole-Body Insulin Resistance in Rodents.

Excess reactive oxygen species (ROS) generation and inflammation may contribute to obesity-associated skeletal muscle insulin resistance. Ghrelin is a gastric hormone whose unacylated form (UnAG) is associated with whole-body insulin sensitivity in humans and may reduce oxidative stress in nonmuscle cells in vitro. We hypothesized that UnAG 1) lowers muscle ROS production and inflammation and enhances tissue insulin action in lean rats and 2) prevents muscle metabolic alterations and normalizes insulin resistance and hyperglycemia in high-fat diet (HFD)-induced obesity.

Gastric bypass-induced weight loss alters obesity-associated patterns of plasma pentraxin-3 and systemic inflammatory markers.

Background: Systemic inflammation contributes to obesity-associated complications. The short pentraxin C-reactive protein (CRP) is a validated inflammatory marker, whereas long pentraxin-3 (PTX3) limits inflammation and is adaptively stimulated by proinflammatory cytokines in vitro. Severely obese (SO) patients (body mass index [BMI]>40] have the highest obesity-associated complications and increasingly undergo surgical treatment.

The association between hematological parameters and insulin resistance is modified by body mass index - results from the North-East Italy MoMa population study.

Objective: Increments in red blood cell count (RBC), hemoglobin (Hb) and hematocrit (Ht) levels are reportedly associated with higher insulin resistance (IR). Obesity may cause IR, but underlying factors remain incompletely defined, and interactions between obesity, hematological parameters and IR are incompletely understood. We therefore determined whether: 1) BMI and obesity per se are independently associated with higher RBC, hemoglobin and hematocrit; 2) hematological parameters independently predict insulin resistance in obese individuals.

Procalcitonin in early rule-in/rule-out of sepsis in SIRS patients admitted to a medical ward.

Background: A relevant amount of patients with clinical suspect of sepsis is admitted and treated in medical wards (MW). These patients have a better prognosis but are older and with more comorbidities compared to those admitted to intensive care units (ICU). Procalcitonin (PCT) is extensively used in emergency departments for the diagnosis of sepsis, but its accuracy in the setting of a MW has not been thoroughly investigated.

Inverse relationship between "a body shape index" (ABSI) and fat-free mass in women and men: Insights into mechanisms of sarcopenic obesity.

Background & Aims: Sarcopenic obesity may be defined by a high fat to fat-free mass (FM/FFM) ratio. Skeletal muscle may be negatively influenced by the pro-inflammatory milieu associated with visceral fat, while the loading effect induced by a heavier body mass index (BMI) may enhance muscle anabolism. Recently, a new anthropometric measure based on waist circumference (A Body Shape Index, ABSI) was developed.

Obesity and high waist circumference are associated with low circulating pentraxin-3 in acute coronary syndrome.

Background: Long pentraxin 3 (PTX3) is a component of the pentraxin superfamily and a potential marker of vascular damage and inflammation, associated with negative outcome in patients with acute coronary syndromes (ACS). Obesity is a risk factor for cardiovascular disease and PTX3 production is reported in abdominal adipose tissue. Low PTX3 is however reported in the obese population, and obesity per se may be associated with less negative ACS outcome.

Insulin downregulates SIRT1 and AMPK activation and is associated with changes in liver fat, but not in inflammation and mitochondrial oxidative capacity, in streptozotocin-diabetic rat.

Background & Aims: Involvement of insulin in diabetes-associated liver triglyceride deposition and its potential pathways remain incompletely defined. SIRT1 may negatively modulate lipogenesis and liver triglyceride accumulation, involving AMP-activated protein kinase (AMPK) activation. In streptozotocin-diabetic rats, we hypothesized that insulin negatively modulates liver SIRT1 and activates AMPK-inhibited lipogenic mediators leading to triglyceride accumulation.