Hepatic glucose release into the circulation is vital for brain function and survival during periods of fasting and is modulated by an array of hormones that precisely regulate plasma glucose levels. ...We have identified a fasting-induced protein hormone that modulates hepatic glucose release. It is the C-terminal cleavage product of profibrillin, and we name it Asprosin. Asprosin is secreted by white adipose, circulates at nanomolar levels, and is recruited to the liver, where it activates the G protein-cAMP-PKA pathway, resulting in rapid glucose release into the circulation. Humans and mice with insulin resistance show pathologically elevated plasma asprosin, and its loss of function via immunologic or genetic means has a profound glucose- and insulin-lowering effect secondary to reduced hepatic glucose release. Asprosin represents a glucogenic protein hormone, and therapeutically targeting it may be beneficial in type II diabetes and metabolic syndrome.
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•Asprosin discovered as a fasting-induced glucogenic protein hormone•Asprosin induces hepatic glucose production by using cAMP as a second messenger•Asprosin is pathologically elevated with human and mouse insulin resistance•Reduction of asprosin protects against metabolic-syndrome-associated hyperinsulinism
Circulating asprosin, a protein hormone, responds to low dietary glucose by triggering the release of liver glucose stores, and the reduction of asprosin protects against the hyperinsulinism associated with metabolic syndrome.
Cancer progresses by evading the immune system. Elucidating diverse immune evasion strategies is a critical step in the search for next-generation immunotherapies for cancer. Here we report that ...cancer cells can hijack the mitochondria from immune cells via physical nanotubes. Mitochondria are essential for metabolism and activation of immune cells. By using field-emission scanning electron microscopy, fluorophore-tagged mitochondrial transfer tracing and metabolic quantification, we demonstrate that the nanotube-mediated transfer of mitochondria from immune cells to cancer cells metabolically empowers the cancer cells and depletes the immune cells. Inhibiting the nanotube assembly machinery significantly reduced mitochondrial transfer and prevented the depletion of immune cells. Combining a farnesyltransferase and geranylgeranyltransferase 1 inhibitor, namely, L-778123, which partially inhibited nanotube formation and mitochondrial transfer, with a programmed cell death protein 1 immune checkpoint inhibitor improved the antitumour outcomes in an aggressive immunocompetent breast cancer model. Nanotube-mediated mitochondrial hijacking can emerge as a novel target for developing next-generation immunotherapy agents for cancer.
Microbial Symbiosis: A Network towards Biomethanation Saha, Shouvik; Basak, Bikram; Hwang, Jae-Hoon ...
Trends in microbiology (Regular ed.),
December 2020, 2020-12-00, 20201201, Letnik:
28, Številka:
12
Journal Article
Recenzirano
Biomethanation through anaerobic digestion (AD) is the most reliable energy harvesting process to achieve waste-to-energy. Microbial communities, including hydrolytic and fermentative bacteria, ...syntrophic bacteria, and methanogenic archaea, and their interspecies symbioses allow complex metabolisms for the volumetric reduction of organic waste in AD. However, heterogeneity in organic waste induces community shifts in conventional anaerobic digesters treating sewage sludge at wastewater treatment plants globally. Assessing the metabolic roles of individual microbial species in syntrophic communities remains a challenge, but such information has important implications for microbially enhanced energy recovery. This review focuses on the alterations in digester microbiome and intricate interspecies networks during substrate variation, symbiosis among the populations, and their implications for biomethanation to aid stable operation in real-scale digesters.
Anaerobic digestion (AD) involves hydrolysis and acidogenesis, acetogenesis, interspecies electron transfers, and methanogenesis.Heterogeneity in organic waste induces community shifts in digester microbiota during AD.Community shifts affect intricate interspecies symbiotic networks and stable biomethanation.Alterations in deterministic factors influence the microbiota, leading to digester perturbation.
Growing energy demand and global climate change are compelling reasons to look for effective utilisation of waste thermal energy and renewable energy resources. Fifteen percent of the electricity ...produced in the whole world is employed for refrigeration and air-conditioning processes of various kinds. Low-temperature heat operated environment-friendly adsorption cooling systems are emerging as viable alternatives to electricity-driven vapour compression refrigeration systems. Comparatively bigger sizes of adsorption based cooling units, due to their low specific cooling power, are preventing successful commercialization of the technology. Efforts are on to enhance the performance of adsorption systems through improvements in adsorbents properties, use of advanced cycles, etc. Recent application of nano-technology in the development of adsorbent material may be a big step forward towards making this technology competitive with available technologies in the market. This paper traces the evolution of the technology and analyses the obstacles to wide spread use of adsorption chillers.
The transcription factor EB (TFEB) is an essential component of lysosomal biogenesis and autophagy for the adaptive response to food deprivation. To address the physiological function of TFEB in ...skeletal muscle, we have used muscle-specific gain- and loss-of-function approaches. Here, we show that TFEB controls metabolic flexibility in muscle during exercise and that this action is independent of peroxisome proliferator-activated receptor-γ coactivator1α (PGC1α). Indeed, TFEB translocates into the myonuclei during physical activity and regulates glucose uptake and glycogen content by controlling expression of glucose transporters, glycolytic enzymes, and pathways related to glucose homeostasis. In addition, TFEB induces the expression of genes involved in mitochondrial biogenesis, fatty acid oxidation, and oxidative phosphorylation. This coordinated action optimizes mitochondrial substrate utilization, thus enhancing ATP production and exercise capacity. These findings identify TFEB as a critical mediator of the beneficial effects of exercise on metabolism.
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•TFEB regulates mitochondrial biogenesis and function in muscle•Glucose homeostasis in skeletal muscle requires TFEB•The effects of TFEB on muscle metabolism are independent from PGC1α•TFEB coordinates metabolic flexibility during physical exercise
Mansueto et al. show that TFEB acts as a central coordinator of skeletal muscle insulin sensitivity, glucose homeostasis, lipid oxidation, and mitochondrial function in the adaptive metabolic response to physical exercise in a PGC1α-independent manner.
Asprosin is a recently discovered fasting-induced hormone that promotes hepatic glucose production. Here we demonstrate that asprosin in the circulation crosses the blood-brain barrier and directly ...activates orexigenic AgRP
neurons via a cAMP-dependent pathway. This signaling results in inhibition of downstream anorexigenic proopiomelanocortin (POMC)-positive neurons in a GABA-dependent manner, which then leads to appetite stimulation and a drive to accumulate adiposity and body weight. In humans, a genetic deficiency in asprosin causes a syndrome characterized by low appetite and extreme leanness; this is phenocopied by mice carrying similar mutations and can be fully rescued by asprosin. Furthermore, we found that obese humans and mice had pathologically elevated concentrations of circulating asprosin, and neutralization of asprosin in the blood with a monoclonal antibody reduced appetite and body weight in obese mice, in addition to improving their glycemic profile. Thus, in addition to performing a glucogenic function, asprosin is a centrally acting orexigenic hormone that is a potential therapeutic target in the treatment of both obesity and diabetes.
Gestational diabetes mellitus (GDM) affects 7-18% of all pregnancies. Despite its high prevalence, there is no widely accepted animal model. To address this, we recently developed a mouse model of ...GDM. The goal of this work was to further characterize this animal model by assessing insulin resistance and beta cell function. Mice were randomly assigned to either control (CD) or high fat, high sugar (HFHS) diet and mated 1 week later. At day 0 (day of mating) mice were fasted and intraperitoneal insulin tolerance tests (ipITT) were performed. Mice were then euthanized and pancreata were collected for histological analysis. Euglycemic hyperinsulinemic clamp experiments were performed on day 13.5 of pregnancy to assess insulin resistance. Beta cell function was assessed by glucose stimulated insulin secretion (GSIS) assay performed on day 0, 13.5 and 17.5 of pregnancy. At day 0, insulin tolerance and beta cell numbers were not different. At day 13.5, glucose infusion and disposal rates were significantly decreased (p<0.05) in Pregnant (P) HFHS animals (p<0.05) suggesting development of insulin resistance in P HFHS dams. Placental and fetal glucose uptake was significantly increased (p<0.01) in P HFHS dams at day 13.5 of pregnancy and by day 17.5 of pregnancy fetal weights were increased (p<0.05) in P HFHS dams compared to P CD dams. Basal and secreted insulin levels were increased in HFHS fed females at day 0, however at day 13.5 and 17.5 GSIS was decreased (p<0.05) in P HFHS dams. In conclusion, this animal model results in insulin resistance and beta cell dysfunction by mid-pregnancy further validating its relevance in studying the pathophysiology GDM.
The lysosomal-autophagic pathway is activated by starvation and plays an important role in both cellular clearance and lipid catabolism. However, the transcriptional regulation of this pathway in ...response to metabolic cues is uncharacterized. Here we show that the transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy, is induced by starvation through an autoregulatory feedback loop and exerts a global transcriptional control on lipid catabolism via Ppargc1α and Ppar1α. Thus, during starvation a transcriptional mechanism links the autophagic pathway to cellular energy metabolism. The conservation of this mechanism in Caenorhabditis elegans suggests a fundamental role for TFEB in the evolution of the adaptive response to food deprivation. Viral delivery of TFEB to the liver prevented weight gain and metabolic syndrome in both diet-induced and genetic mouse models of obesity, suggesting a new therapeutic strategy for disorders of lipid metabolism.
A proper waste management practice such as anaerobic digestion for the waste generated by the agro-food industries could minimize the amount of material disposal to landfill. In our study, the ...improvement of methane production was elucidated through the pretreatment optimization of the mixed fruit wastes (FW). Dilute acetic acid pretreatment of FW was optimized in order to increase the bioavailability and microbial accessibility. A maximum sugar recovery of 95% was achieved from the pretreated FW under the optimized conditions (0.2 M acetic acid, 62.5 °C, and 30 min). Fourier transform infrared spectroscopy (FTIR) and Thermogravimetric (TG) analyses verified the presence of cellulosic material in the pretreated FW. X-ray diffraction (XRD) analysis indicated that the crystallinity index was increased to 56% after the disruption of complex hemicellulosic structures during pretreatment. Increased porosity and surface roughness of pretreated FW for better microbial attachment were confirmed in scanning electron microscopy (SEM). Anaerobic digestion showed increased methanogenic activity (10.17 mL g−1 VSinitial d−1) in pretreated FW, during 86-day experimental period due to better microbial attachment and accessibility during the digestion process. Higher methane yield of 53.58 mL g−1 VSinitial was observed in pretreated FW. Thus, acetic acid pretreatment is an effective method to improve the utilization and conversion of FW to methane.
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•Fruit waste pretreatment was optimized by employing RSM.•Under optimized conditions, pretreatment recovered 95% of the total sugar.•Optimized pretreatment improved methane yield by 10%.
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