9 research outputs found

    Special considerations for the adolescent with obesity: An obesity medicine association (OMA) clinical practice statement (CPS) 2024

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    BACKGROUND: This Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) details special considerations for the management of the adolescent with obesity. The information in this CPS is based on scientific evidence, supported by medical literature, and derived from the clinical experiences of members of the OMA. METHODS: The scientific information and clinical guidance in this CPS are based on scientific evidence, supported by the medical literature, and derived from the clinical perspectives of the authors. RESULTS: This OMA Clinical Practice Statement addresses special considerations in the management and treatment of adolescents with overweight and obesity. CONCLUSIONS: This OMA Clinical Practice Statement on the adolescent with obesity is an overview of current recommendations. These recommendations provide a roadmap to the improvement of the health of adolescents with obesity, especially those with metabolic, physiological, and psychological complications. This CPS also addresses treatment recommendations and is designed to help the provider with clinical decision making

    ALDOC- and ENO2- driven glucose metabolism sustains 3D tumor spheroids growth regardless of nutrient environmental conditions: a multi-omics analysis

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    BackgroundMetastases are the major cause of cancer-related morbidity and mortality. By the time cancer cells detach from their primary site to eventually spread to distant sites, they need to acquire the ability to survive in non-adherent conditions and to proliferate within a new microenvironment in spite of stressing conditions that may severely constrain the metastatic process. In this study, we gained insight into the molecular mechanisms allowing cancer cells to survive and proliferate in an anchorage-independent manner, regardless of both tumor-intrinsic variables and nutrient culture conditions.Methods3D spheroids derived from lung adenocarcinoma (LUAD) and breast cancer cells were cultured in either nutrient-rich or -restricted culture conditions. A multi-omics approach, including transcriptomics, proteomics, and metabolomics, was used to explore the molecular changes underlying the transition from 2 to 3D cultures. Small interfering RNA-mediated loss of function assays were used to validate the role of the identified differentially expressed genes and proteins in H460 and HCC827 LUAD as well as in MCF7 and T47D breast cancer cell lines.ResultsWe found that the transition from 2 to 3D cultures of H460 and MCF7 cells is associated with significant changes in the expression of genes and proteins involved in metabolic reprogramming. In particular, we observed that 3D tumor spheroid growth implies the overexpression of ALDOC and ENO2 glycolytic enzymes concomitant with the enhanced consumption of glucose and fructose and the enhanced production of lactate. Transfection with siRNA against both ALDOC and ENO2 determined a significant reduction in lactate production, viability and size of 3D tumor spheroids produced by H460, HCC827, MCF7, and T47D cell lines.ConclusionsOur results show that anchorage-independent survival and growth of cancer cells are supported by changes in genes and proteins that drive glucose metabolism towards an enhanced lactate production. Notably, this finding is valid for all lung and breast cancer cell lines we have analyzed in different nutrient environmental conditions. broader Validation of this mechanism in other cancer cells of different origin will be necessary to broaden the role of ALDOC and ENO2 to other tumor types. Future in vivo studies will be necessary to assess the role of ALDOC and ENO2 in cancer metastasis

    Preclinical model in HCC: The SGK1 kinase inhibitor SI113 blocks tumor progression in vitro and in vivo and synergizes with radiotherapy

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    Here, we characterize in depth a novel potent and selective pyrazolo[3,4-d]pyrimidine-based SGK1 inhibitor. This compound, named SI113, active in vitro in the sub-micromolar range, inhibits SGK1-dependent signaling in cell lines in a dose- and time-dependent manner. We recently showed that SI113 slows down tumor growth and induces cell death in colon carcinoma cells, when used in monotherapy or in combination with paclitaxel. We now demonstrate for the first time that SI113 inhibits tumour growth in hepatocarcinoma models in vitro and in vivo. SI113-dependent tumor inhibition is dose- and time-dependent. In vitro and in vivo SI113-dependent SGK1 inhibition determined a dramatic increase in apotosis/necrosis, inhibited cell proliferation and altered the cell cycle profile of treated cells. Proteome-wide biochemical studies confirmed that SI113 down-regulates the abundance of proteins downstream of SGK1 with established roles in neoplastic transformation, e.g. MDM2, NDRG1 and RAN network members. Consistent with knock-down and over-expressing cellular models for SGK1, SI113 potentiated and synergized with radiotherapy in tumor killing. No short-term toxicity was observed in treated animals during in vivo SI113 administration. These data show that direct SGK1 inhibition can be effective in hepatic cancer therapy, either alone or in combination with radiotherapy

    Genetic Variation in Innate Immunity, Diet and Biomarkers of the Metabolic Syndrome

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    Chronic low-grade inflammation is associated the Metabolic Syndrome (MetS) and may contribute to its development. A diet high in saturated fat (SFA) has been associated with increased inflammation and development of the MetS. SFAs have been shown to elicit pro-inflammatory signaling through proteins of innate immunity, TLR4 and Nods 1 and 2. We determined whether common polymorphisms in the genes of these proteins could modify the association between fat intake and biomarkers of the MetS. Fat intake was measured using a food frequency questionnaire and genotyping was completed using real-time PCR. The TLR4 Asp299Gly (rs4986790) polymorphism was associated with decreased insulin sensitivity while an intronic polymorphism (rs5030728) modified the association between dietary SFA and HDL-cholesterol. The Nod1 Glu266Lys polymorphism modified the association between dietary SFA and HOMA-IR. These results suggest a role for innate immunity in mediating some of the effects of dietary SFAs on factors associated with the MetS.MAS

    The role of inflammation in metabolic syndrome

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    The metabolic consequences of obesity have made this highly prevalent condition one of the most common risk factors for type 2 diabetes, hypertension and atherosclerosis. Simultaneous occurrence of these conditions can be explained through the manifestations of metabolic syndrome [MetS]. Clinical indication of MetS is characterized by a clustering of risk factors for complex chronic diseases which all feature metabolic deterioration as a common component. Diagnosis of MetS can be made if a patient exhibits three of the identified risk factors, some of which include: elevated waist circumference, elevated triglycerides, low high density lipoprotein levels, hypertension and elevated blood glucose. The progression from obesity to MetS involves an alteration in body metabolism mediated by cytokines- signalling molecules that coordinate the inflammatory response. Increased visceral adipose tissue contributes to augmented secretion of pro-inflammatory cytokines which can activate several transcription factors, including NF-κB, which promote these inflammatory conditions and lead to increased oxidative stress. Exacerbation of the condition then ensues as oxidative stress results in oxidized low density lipoprotein, dyslipidemia, insulin resistance, hypertension and atherogenesis. This review will not only focus on the role of inflammation in the manifestations of MetS, but also outlines some lifestyle and nutritional treatments that can be used to treat the condition and reduce the risk of chronic disease
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