Many cancer therapies produce toxic side effects whose molecular mechanisms await full elucidation. The most feared and studied side effect of chemotherapeutic drugs is cardiotoxicity. Also, skeletal muscle physiology impairment has been recorded after many chemotherapeutical treatments. However, only doxorubicin has been extensively studied for its side effects on skeletal muscle. Chemotherapeutic‐induced adverse side effects are, in many cases, mediated by mitochondrial damage. In particular, trastuzumab and sunitinib toxicity is mainly associated with mitochondria impairment and is mostly reversible. Vice versa, doxorubicin‐induced toxicity not only includes mitochondria damage but can also lead to a more robust and extensive cell injury which is often irreversible and lethal. Drugs interfering with mitochondrial functionality determine the depletion of ATP reservoirs and lead to subsequent reversible contractile dysfunction. Mitochondrial damage includes the impairment of the respiratory chain and the loss of mitochondrial membrane potential with subsequent disruption of cellular energetic. In a context of increased stress, AMPK has a key role in maintaining energy homeostasis, and inhibition of the AMPK pathway is one of the proposed mechanisms possibly mediating mitochondrial toxicity due to chemotherapeutics. Therapies targeting and protecting cell metabolism and energy management might be useful tools in protecting muscular tissues against the toxicity induced by chemotherapeutic drugs.

RANKL/RANK/OPG system consists of three essential signaling molecules: i) the receptor activator of nuclear factor (NF)-kB-ligand (RANKL), ii) the receptor activator of NF-kB (RANK), and iii) the soluble decoy receptor osteoprotegerin (OPG). Although this system is critical for the regulation of osteoclast differentiation/activation and calcium release from the skeleton, different studies have elucidated its specific role in mammary gland physiology and hormone-driven epithelial proliferation during pregnancy. Of note, several data suggest that progesterone induces mammary RANKL expression in mice and humans. In turn, RANKL controls cell proliferation in breast epithelium under physiological conditions typically associated with higher serum progesterone levels, such as luteal phase of the menstrual cycle and pregnancy. Hence, RANKL/RANK system can be regarded as a major downstream mediator of progesterone-driven mammary epithelial cells proliferation, potentially contributing to breast cancer initiation and progression. Expression of RANKL, RANK, and OPG has been detected in breast cancer cell lines and in human primary breast cancers. To date, dysregulation of RANKL/RANK/OPG system at the skeletal level has been widely documented in the context of metastatic bone disease. In fact, RANKL inhibition through the RANKL-blocking human monoclonal antibody denosumab represents a well-established therapeutic option to prevent skeletal-related events in metastatic bone disease and adjuvant therapy-induced bone loss in breast cancer. On the other hand, the exact role of OPG in breast tumorigenesis is still unclear. This review focuses on molecular mechanisms linking RANKL/RANK/OPG system to mammary tumorigenesis, highlighting pre-clinical and clinical evidence for the potential efficacy of RANKL inhibition as a prevention strategy and adjuvant therapy in breast cancer settings.

Legumes are nutrient-dense crops with health-promoting benefits. However, several barriers are associated with their consumption. Emerging issues including food neophobic tendencies or taboos, unclear dietary guidelines on legume consumption, health concerns, and socio-economic reasons, as well as long cooking procedures, adversely affect legume consumption frequency. Pre-treatment methods, including soaking, sprouting, and pulse electric field technology, are effective in reducing the alpha-oligosaccharides and other anti-nutritional factors, eventually lowering cooking time for legumes. Extrusion technology used for innovative development of legume-enriched products, including snacks, breakfast cereals and puffs, baking and pasta, represents a strategic way to promote legume consumption. Culinary skills such as legume salads, legume sprouts, stews, soups, hummus, and the development of homemade cake recipes using legume flour could represent effective ways to promote legume consumption. This review aims to highlight the nutritional and health effects associated with legume consumption, and strategies to improve their digestibility and nutritional profile. Additionally, proper educational and culinary approaches aimed to improve legumes intake are discussed.

Skeletal muscle is essential to maintain vital functions such as movement, breathing, and thermogenesis, and it is now recognized as an endocrine organ. Muscles release factors named myokines, which can regulate several physiological processes. Moreover, skeletal muscle is particularly important in maintaining body homeostasis, since it is responsible for more than 75% of all insulin-mediated glucose disposal. Alterations of skeletal muscle differentiation and function, with subsequent dysfunctional expression and secretion of myokines, play a key role in the pathogenesis of obesity, type 2 diabetes, and other metabolic diseases, finally leading to cardiometabolic complications. Hence, a deeper understanding of the molecular mechanisms regulating skeletal muscle function related to energy metabolism is critical for novel strategies to treat and prevent insulin resistance and its cardiometabolic complications. This review will be focused on both cellular and animal models currently available for exploring skeletal muscle metabolism and endocrine function.

The novel coronavirus disease (COVID-19) is posing a serious challenge to the health-care systems worldwide, with an enormous impact on health conditions and loss of lives. Notably, obesity and its related comorbidities are strictly related with worse clinical outcomes of COVID-19 disease. Recently, there is a growing interest in the clinical use of ketogenic diets (KDs), particularly in the context of severe obesity with related metabolic complications. KDs have been proven effective for a rapid reduction of fat mass, preserving lean mass and providing an adequate nutritional status. In particular, the physiological increase in plasma levels of ketone bodies exerts important anti-inflammatory and immunomodulating effects, which may reveal as precious tools to prevent infection and potential adverse outcomes of COVID-19 disease. We discuss here the importance of KDs for a rapid reduction of several critical risk factors for COVID-19, such as obesity, type 2 diabetes and hypertension, based on the known effects of ketone bodies on inflammation, immunity, metabolic profile and cardiovascular function. We do believe that a rapid reduction of all modifiable risk factors, especially obesity with its metabolic complications, should be a pillar of public health policies and interventions, in view of future waves of SARS-CoV-2 infection.

Background/Objectives: Obesity is a global health problem with significant chronic disease risks. This study examined gender differences in eating behaviour, body composition, eating frequency and time of hunger in an Italian cohort with obesity (BMI ≥ 30) to inform gender-specific management strategies. Methods: A retrospective analysis of 720 adults (51.5% female, mean age 44.4 ± 13.8 years) assessed body composition and eating behaviour using principal component analysis (PCA) to classify eating profiles (structured, irregular, social and disordered/impulsive eaters). Results: Males showed higher weight, abdominal circumference and fat mass, while females showed higher fat mass percentages (p < 0.001). Gender differences were observed in the frequency of meals (e.g., 54.7% of males and 64.7% of females consumed 4–5 meals per day, p = 0.0018) and the time of hunger (males: before dinner; females: morning hunger, p = 0.005). The PCA profiles revealed that the ‘structured eaters’ had a healthier body composition, whereas the ‘disordered/impulsive eaters’ had a higher fat mass. Irregular eaters were predominantly male (41.0%), while disordered eaters were predominantly female (39.9%) (p = 0.0016). Conclusions: Gender-specific eating patterns influence obesity outcomes. Structured eating was associated with healthier profiles, whereas impulsive or irregular patterns were related to higher fat mass. The retrospective design and non-validated questionnaire for dietary behaviour assessment limit generalisability, warranting further research for tailored interventions. Registration: ClinicalTrials.gov (NCT06654674).