Diabetes mellitus and cardiovascular diseases : nutraceutical interventions related to caloric restriction

Type 2 diabetes (T2DM) and cardiovascular disease (CVD) are closely associated and represent a key public health problem worldwide. An excess of adipose tissue, NAFLD, and gut dysbiosis establish a vicious circle that leads to chronic inflammation and oxidative stress. Caloric restriction (CR) is the most promising nutritional approach capable of improving cardiometabolic health. However, adherence to CR represents a barrier to patients and is the primary cause of therapeutic failure. To overcome this problem, many different nutraceutical strategies have been designed. Based on several data that have shown that CR action is mediated by AMPK/SIRT1 activation, several nutraceutical compounds capable of activating AMPK/SIRT1 signaling have been identified. In this review, we summarize recent data on the possible role of berberine, resveratrol, quercetin, and L-carnitine as CR-related nutrients. Additionally, we discuss the limitations related to the use of these nutrients in the management of T2DM and CVD

Editorial for the Special Issue “Effects of COVID-19 on Lifestyle Behaviors in Children with Obesity”

During the last four decades, the prevalence of obesity has increased dramatically worldwide; concomitantly, a progressive rise in the prevalence of obesity, diabetes, and other nutrition-related chronic diseases has also been observed in childhood [...]

May the force be with you: why resistance training is essential for subjects with type 2 diabetes mellitus without complications

Physical activity, together with diet and pharmacological therapy, represents one of the three cornerstones in type 2 diabetes mellitus treatment and care. The therapeutic appeal of regular physical activity stems from: (i) its non-pharmacological nature; (ii) its beneficial effects on the metabolic risk factors associated with diabetes complications; (iii) its low costs. Evidence accumulated in the last years suggests that aerobic training\u2014endurance training\u2014constitutes a safe modality of intervention, achievable, and effective in diabetes treatment, whenever it is not limited by comorbidities. Aerobic training exerts insulin-mimetic effects and has been shown to lower mortality risk too. Anaerobic, intense physical activity, such as that of strength or power sports disciplines, is not univocally recognized as safe and simple to realize, however, it is important in stimulating energy and glucose metabolism. According to recent evidence, high-intensity training may be prescribed even in the face of cardiovascular diseases, peripheral vascular disease, or osteoarthritis. Some studies have shown resistance training to be more efficient than aerobic exercise in improving glycemic control. This review explores the most up-to-date indications emerging from literature in support of the beneficial effects of strength stimulation and resistance training in patients with type 2 diabetes without complications

Sugars, exercise and health

Background: There is a direct link between a variety of addictions and mood states to which exercise could be relieving. Sugar addiction has been recently counted as another binge/compulsive/addictive eating behavior, differently induced, leading to a high-significant health problem. Regularly exercising at moderate intensity has been shown to efficiently and positively impact upon physiological imbalances caused by several morbid conditions, including affective disorders. Even in a wider set of physchiatric diseases, physical exercise has been prescribed as a complementary therapeutic strategy. Method: A comprehensive literature search was carried out in the Cochrane Library and MEDLINE databases (search terms: sugar addiction, food craving, exercise therapy, training, physical fitness, physical activity, rehabilitation and aerobic). Results: Seeking high-sugar diets, also in a reward- or craving-addiction fashion, can generate drastic metabolic derangements, often interpolated with affective disorders, for which exercise may represent a valuable, universal, non-pharmachological barrier. Limitations: More research in humans is needed to confirm potential exercise-mechanisms that may break the bond between sugar over-consumption and affective disorders. Conclusions: The purpose of this review is to address the importance of physical exercise in reversing the gloomy scenario of unhealthy diets and sedentary lifestyles in our modern society

Exercise has the guts: how physical activity may positively modulate gut microbiota in chronic and immune-based diseases

Limited animal and human research findings suggests that exercise might have a beneficial role for health gut. Cardiorespiratory fitness correlates with health-associated gut parameters such as taxonomic diversity and richness. Physical exercise may augment intestinal microbial diversity through several mechanisms including promotion of an anti-inflammatory state. Disease-associated microbial functions were linked to distinct taxa in previous studies of familial type 1 diabetes mellitus (T1D). An integrated multi-approach in the study of T1D, including physical exercise, is advocated. The present review explores how exercise might modulate gut microbiota and microbiome characteristics in chronic and immune-based diseases, given the demonstrated relationship between gut function and human health

Immunosuppressive therapy in pancreas and islet transplant : Need for simultaneous assessment of insulin sensitivity and secretion

Diabetes mellitus is a metabolic disease possi- ble to treat via pancreas/islet transplantation but most immunosuppressive drugs are diabeto- genic. In this letter, we review current up to date methods to assess insulin action and secretion (using the surrogate indexes) suggesting their use in large studies in populations of pancreas/ islets transplanted patients

Plasma Citrulline : a New Marker of Gut Epithelium Alteration in Obese Patients?

Objectives: In the last decade gut microbial diversity was associated with the pathogenesis of obesity in humans. Plasma citrulline was a simple and accurate biomarker for the severity of intestinal failure and was associated with short bowel syndrome and alteration of gut permeability, being developed as an alternative to D-xylose tolerance test for the diagnosis of an abnormal small intestinal absorption of nutrients. This study was performed to ascertain whether obesity might be associated with dysregulation of epithelial gut function. Methods: Fifteen obese individuals (5 M/10 F; BMI 37.4 \ub1 6.1 Kg/m2; 42 \ub1 6 yrs) and 15 healthy gender- and age-matched controls (6 M/9 F BMI: 22.7 \ub1 2.1 Kg/m2; 39 \ub1 7 yrs) underwent D-xylose load (25 g) and plasma citrulline, plasma insulin, glucose and lipid profile testing. Results: Plasma citrulline was significantly lower in the obese group (p = 0.045) with respect to controls, whilst total cholesterol, LDL and tryglicerides concentration, insulin level and HOMA-IR were significantly higher in obese patients. In contrast, after D-xylose load no difference in serum xylose was found between the two groups (p = ns). Conclusions: Obese patients show a decreased citrulline concentration with respect to lean subjects. Since citrulline is a known marker of intestinal health, alterations in the gut epithelium are likely to be associated with the obesity syndrome. We propose to measure citrulline level in obese patients on a routine basis

L-Carnitine counteracts in vitro fructose-induced hepatic steatosis through targeting oxidative stress markers

Purpose: Nonalcoholic fatty liver disease (NAFLD) is defined by excessive lipid accumulation in the liver and involves an ample spectrum of liver diseases, ranging from simple uncomplicated steatosis to cirrhosis and hepatocellular carcinoma. Accumulating evidence demonstrates that high fructose intake enhances NAFLD development and progression promoting inhibition of mitochondrial \u3b2-oxidation of long-chain fatty acids and oxidative damages. l-Carnitine (LC), involved in \u3b2-oxidation, has been used to reduce obesity caused by high-fat diet, which is beneficial to ameliorating fatty liver diseases. Moreover, in the recent years, various studies have established LC anti-oxidative proprieties. The objective of this study was to elucidate primarily the underlying anti-oxidative mechanisms of LC in an in vitro model of fructose-induced liver steatosis. Methods: Human hepatoma HepG2 cells were maintained in medium supplemented with LC (5 mM LC) with or without 5 mM fructose (F) for 48 h and 72 h. In control cells, LC or F was not added to medium. Fat deposition, anti-oxidative, and mitochondrial homeostasis were investigated. Results: LC supplementation decreased the intracellular lipid deposition enhancing AMPK activation. However, compound C (AMPK inhibitor-10 \u3bcM), significantly abolished LC benefits in F condition. Moreover, LC, increasing PGC1 \u3b1 expression, ameliorates mitochondrial damage-F induced. Above all, LC reduced ROS production and simultaneously increased protein content of antioxidant factors, SOD2 and Nrf2. Conclusion: Our data seemed to show that LC attenuate fructose-mediated lipid accumulation through AMPK activation. Moreover, LC counteracts mitochondrial damages and reactive oxygen species production restoring antioxidant cellular machine. These findings provide new insights into LC role as an AMPK activator and anti-oxidative molecule in NAFLD

Modulation of cell cycle progression by 5-azacytidine is associated with early myogenesis induction in murine myoblasts

Myogenesis is a multistep process, in which myoblasts withdraw from the cell cycle, cease to divide, elongate and fuse to form multinucleated myotubes. Cell cycle transition is controlled by a family of cyclin-dependent protein kinases (CDKs) regulated by association with cyclins, negative regulatory subunits and phosphorylation. Muscle differentiation is orchestrated by myogenic regulatory factors (MRFs), such as MyoD and Myf-5. DNA methylation is crucial in transcriptional control of genes involved in myogenesis. Previous work has indicated that treatment of fibroblasts with the DNA-demethylating agent 5-azacytidine (AZA) promotes MyoD expression. We studied the effects of AZA on cell cycle regulation and MRFs synthesis during myoblast proliferation and early myogenesis phases in C2C12 cells. During the proliferation phase, cells were incubated in growth medium with 5\u3bcM AZA (GMAZA) or without AZA (GM) for 24 hours. At 70% confluence, cells were kept in growth medium in order to spontaneously achieve differentiation or transferred to differentiation medium with 5\u3bcM AZA (DMAZA) or without AZA (DM) for 12 and 24 hours. Cells used as control were unstimulated. In the proliferation phase, AZA-treated cells seemed to lose their characteristic circular shape and become elongated. The presence of AZA resulted in significant increases in the protein contents of Cyclin-D (FC:1.23 GMAZA vs GM p 640.05), p21 (FC: 1.23 GMAZA vs GM p 640.05), Myf-5 (FC: 1.21 GMAZA vs GM p 640.05) and MyoD (FC: 1.20 GMAZA vs GM p 640.05). These results propose that AZA could inhibit cell proliferation. During 12 hours of differentiation, AZA decreased the downregulation of genes involved in cell cycle arrest and in restriction point (G1 and G1/S phase) and the expression of several cyclins, E2F Transcription Factors, cyclin-dependent kinase inhibitors, specific genes responsible of cell cycle negative regulation. During 24 hours of differentiation, AZA induced an increment in the protein expression of Myf-5 (FC: 1.57 GMAZA vs GM p 640.05), MyoD (FC: 1.14 DM vs GM p 640.05; FC: 1.47 DMAZA vs GM p 640.05), p21 (FC: 1.36 GMAZA vs GM p 640.01; FC: 1.49 DM vs GM p 640.05; FC: 1.82 DMAZA vs GM p 640.01) and MyHC (FC: 1.40 GMAZA vs GM p 640.01; FC: 2.39 DM vs GM p 640.05; FC: 3.51 DMAZA vs GM p 640.01). Our results suggest that AZA-induced DNA demethylation can modulate cell cycle progression and enhance myogenesis. The effects of AZA may open novel clinical uses in the field of muscle injury research and treatment

Reduction of impulsivity in patients receiving deep transcranial magnetic stimulation treatment for obesity

Purpose: Aims of the present study were to investigate a wide array of psychological symptoms through validated psychometric tests, before and after 5 weeks of deep Transcranial Magnetic Stimulation (dTMS) in individuals with obesity, and to identify possible relationships with neuroendocrine parameters. Methods: Forty-five patients with obesity (33 F, 12 M; age 48.8 ± 9.9 years; body wt 97.6 ± 14.2 Kg; BMI 36.2 ± 4.2) were randomized into two groups: 26 received high frequency (HF) dTMS and 19 Sham stimulation for 5 weeks. At baseline and after the 5-week treatment, all patients underwent the following psychometric evaluations: Food Cravings Questionnaire-Trait (FCQ-T) and its subscales, Barratt Impulsiveness Scale-11 (BIS-11), State and Trait Anxiety Inventory (STAI-y1 and STAI-y2), and Beck Depression Inventory (BDI). Hormonal and neuroendocrine markers were assessed at the first and last dTMS session. Results: By adjusting for baseline variables and treatment arms, a significant decrease in body wt and BMI was found in HF group, both with univariate (p = 0.019) and multivariate analyses (p = 0.012). Impulsivity significantly decreased in HF group, both with univariate (p = 0.031) and multivariate analyses (p = 0.011). A positive association between the impulsivity score change and the leptin level variation (p = 0.031) was found. Conclusion: The decrease of impulsivity together with the BMI reduction in individuals with obesity, treated with real stimulation, suggests that impulsivity may be a risk factor for obesity. Treatment with dTMS revealed to be effective in reducing both BMI and impulsivity by enhancing inhibitory capacity of Pre-Frontal Cortex (PFC), and modulating neuroendocrine system, especially leptin