Understanding cachexia as a cancer metabolism syndrome

Metabolic reprogramming occurs in tumors to foster cancer cell proliferation, survival and metastasis, but as well at a systemic level affecting the whole organism, eventually leading to cancer cachexia. Indeed, as cancer cells rely on external sources of nitrogen and carbon skeleton to grow, systemic metabolic deregulation promoting tissue wasting and metabolites mobilization ultimately supports tumor growth. Cachectic patients experience a wide range of symptoms affecting several organ functions such as muscle, liver, brain, immune system and heart, collectively decreasing patients’ quality of life and worsening their prognosis. Moreover, cachexia is estimated to be the direct cause of at least 20% of cancer deaths. The main aspect of cachexia syndrome is the unstoppable skeletal muscle and fat storage wasting, even with an adequate caloric intake, resulting in nutrient mobilization – both directly as lipid and amino acids and indirectly as glucose derived from the exploitation of liver gluconeogenesis – that reaches the tumor through the bloodstream. From a metabolic standpoint, cachectic host develops a wide range of dysfunctions, from increased insulin and IGF-1 resistance to induction of mitochondrial uncoupling proteins and fat tissue browning resulting in an increased energy expenditure and heat generation, even at rest. For a long time, cachexia has been merely considered an epiphenomenon of end-stage tumors. However, in specific tumor types, such as pancreatic cancers, it is now clear that patients present markers of tissue wasting at a stage in which tumor is not yet clinically detectable, and that host amino acid supply is required for tumor growth. Indeed, tumor cells actively promote tissue wasting by secreting specific factors such as parathyroid hormone-related protein and micro RNAs. Understanding the molecular and metabolic mediators of cachexia will not only advance therapeutic approaches against cancer, but also improve patients’ quality of life

Testing a model of pacific oysters’ (Crassostrea gigas) growth in the adriatic sea: Implications for aquaculture spatial planning

Assessing the potential biomass yield is a key step in aquaculture site selection. This is challenging, especially for shellfish, as the growth rate depends on both trophic status and water temperature. Individual ecophysiological models can be used for mapping potential shellfish growth in coastal areas, using as input spatial time series of remotely sensed SST and chlorophyll-a. This approach was taken here to estimate the potential for developing oyster (Crassostrea gigas) farming in the western Adriatic Sea. Industry relevant indicators (i.e., shell length, total individual weight) and days required to reach marketable size were mapped using a dynamic energy budget model, finetuned on the basis of site-specific morphometric data collected monthly for a year. Spatially scaled-up results showed that the faster and more uniform growth in the northern Adriatic coastal area, compared with the southern one, where chlorophyll-a levels are lower and summer temperatures exceed the critical temperature limit for longer periods. These results could be used in planning the identification of allocated zones for aquaculture, (AZA), taking into account also the potential for farming or co-farming C. gigas. In perspective, the methodology could be used for getting insights on changes to the potential productivity indicators due to climatic changes

Long-term antigen exposure irreversibly modifies metabolic requirements for T cell function

Energy metabolism is essential for T cell function. However, how persistent antigenic stimulation affects T cell metabolism is unknown. Here, we report that long-term in vivo antigenic exposure induced a specific deficit in numerous metabolic enzymes. Accordingly, T cells exhibited low basal glycolytic flux and limited respiratory capacity. Strikingly, blockade of inhibitory receptor PD-1 stimulated the production of IFNγ in chronic T cells, but failed to shift their metabolism towards aerobic glycolysis, as observed in effector T cells. Instead, chronic T cells appeared to rely on oxidative phosphorylation (OXPHOS) and fatty acid oxidation (FAO) to produce ATP for IFNγ synthesis. Check-point blockade, however, increased mitochondrial production of superoxide and reduced viability and effector function. Thus, in the absence of a glycolytic switch, PD-1-mediated inhibition appears essential for limiting oxidative metabolism linked to effector function in chronic T cells, thereby promoting survival and functional fitness.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Diacylglycerol kinase-α phosphorylation by Src on Y335 is required for activation, membrane recruitment and Hgf-induced cell motility

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Gut microbiota-derived propionate reduces cancer cell proliferation in the liver

Peer reviewedPublisher PD