Metabolic interplays between the tumour and the host shape the tumour macroenvironment

Nature reviews. Cancer, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 20, 2025

Language: Английский

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The role of dietary fibers in regulating appetite, an overview of mechanisms and weight consequences

Critical Reviews in Food Science and Nutrition, Journal Year: 2022, Volume and Issue: 64(10), P. 3139 - 3150

Published: Oct. 4, 2022

Dietary fibers prevent obesity through reduction of hunger and prolongation satiety. A number mechanical endocrine signals from gastrointestinal tract are stimulated by their fermentation products, reach regions brain involved in the regulation appetite, ultimately reduce food intake. Gastric distention, delayed gastric emptying, prevention hypoglycemic, increased amounts unabsorbed nutrients reaching to ileum, stimulation enteroendocrine cells for secretion cholecystokinin, glucagon-like peptide-1 (GLP-1), peptide YY among mechanisms decreasing Fermentation produces short-chain fatty acids that also stimulates secrete GLP-1 PYY. Randomized controlled trials have shown reductions energy intake body weight along with satiation reduced following consumption fibers. Prospective cohort studies confirmed these results but extent loss some has been small. Controversies exist between particularly effect on hormones, subsequent intake, resultant loss. More needed before a clear conclusion can be drawn especially appetite-related hormones

Language: Английский

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Inhalation of diesel exhaust particulate matter accelerates weight gain via regulation of hypothalamic appetite-related genes and gut microbiota metabolism

Journal of Hazardous Materials, Journal Year: 2024, Volume and Issue: 466, P. 133570 - 133570

Published: Jan. 21, 2024

Language: Английский

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Myokines: metabolic regulation in obesity and type 2 diabetes

Life Metabolism, Journal Year: 2024, Volume and Issue: 3(3)

Published: Feb. 29, 2024

Skeletal muscle plays a vital role in the regulation of systemic metabolism, partly through its secretion endocrine factors which are collectively known as myokines. Altered myokine levels associated with metabolic diseases, such type 2 diabetes (T2D). The significance interorgan crosstalk, particularly myokines, has emerged fundamental aspect nutrient and energy homeostasis. However, comprehensive understanding biology setting obesity T2D remains major challenge. In this review, we discuss biological functions key myokines that have been extensively studied during past two decades, namely interleukin 6 (IL-6), irisin, myostatin (MSTN), growth differentiation factor 11 (GDF11), fibroblast 21 (FGF21), apelin, brain-derived neurotrophic (BDNF), meteorin-like (Metrnl), secreted protein acidic rich cysteine (SPARC), β-aminoisobutyric acid (BAIBA), Musclin, Dickkopf 3 (Dkk3). Related to these, detail exercise expression together their contributions physiology disease. Despite significant advancements research, many remain challenging measure accurately investigate thoroughly. Hence, new research techniques detection methods should be developed rigorously tested. Therefore, developing perspective on is crucial, will likely offer insights into pathophysiological mechanisms underlying may reveal novel targets for therapeutic interventions.

Language: Английский

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Melanocortin-3 receptor expression in AgRP neurons is required for normal activation of the neurons in response to energy deficiency

Cell Reports, Journal Year: 2023, Volume and Issue: 42(10), P. 113188 - 113188

Published: Oct. 1, 2023

The melanocortin-3 receptor (MC3R) is a negative regulator of the central melanocortin circuitry via presynaptic expression on agouti-related protein (AgRP) nerve terminals, from where it regulates GABA release onto secondary MC4R-expressing neurons. However, MC3R knockout (KO) mice also exhibit defective behavioral and neuroendocrine responses to fasting. Here, we demonstrate that KO activation AgRP neurons in response fasting, cold exposure, or ghrelin while exhibiting normal inhibition by sensory detection food ad libitum-fed state. Using conditional model, show control neuron fasting requires specific presence within Thus, crucial player responsiveness soma both hormonal neuronal signals energy need.

Language: Английский

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The immunology of sickness metabolism

Cellular and Molecular Immunology, Journal Year: 2024, Volume and Issue: 21(9), P. 1051 - 1065

Published: Aug. 6, 2024

Everyone knows that an infection can make you feel sick. Although we perceive infection-induced changes in metabolism as a pathology, they are part of carefully regulated process depends on tissue-specific interactions between the immune system and organs involved regulation systemic homeostasis. Immune-mediated homeostatic parameters lead to altered production uptake nutrients circulation, which modifies metabolic rate key organs. This is what experience being The purpose sickness generate environment body optimally able fight while denying vital for replication pathogens. Sickness cells, mediate responses tailored nature magnitude threat. As increases severity, so do number type cells level affected, dictates degree Interestingly, many alterations associated with disease appear overlap immune-mediated observed following infection. Targeting processes involving activated therefore holds great potential treating both people severe those disease. In this review, will discuss how communicates situ homeostasis communication impacted by

Language: Английский

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Decoding the role of ghrelin and its interactions with central signaling pathways in avian appetite regulation

Veterinary Research Communications, Journal Year: 2025, Volume and Issue: 49(2)

Published: Jan. 13, 2025

Language: Английский

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The role of the hypothalamus in the development of cancer cachexia

Physiology & Behavior, Journal Year: 2025, Volume and Issue: unknown, P. 114909 - 114909

Published: April 1, 2025

Language: Английский

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A Comparison Between High- and Low-Performing Lambs and Their Impact on the Meat Quality and Development Level Using a Multi-Omics Analysis of Rumen Microbe–Muscle–Liver Interactions

Microorganisms, Journal Year: 2025, Volume and Issue: 13(4), P. 943 - 943

Published: April 19, 2025

Through an integrated multi-omics analysis of rumen microbial communities, muscle transcriptomes, metabolic profiles, and liver this study systematically compared high- low-performing lambs to elucidate their divergent effects on meat quality attributes growth development. A total 100 male with similar birth weight (3.07 ± 0.06 kg) were selected within 72 h. All test synchronized weaning at 45 days age uniformly fed the same diet (total mixed ration) in pen until 180 age, ad libitum access food water throughout period. Subsequently, eight highest (HADG) lowest (LADG) average daily gains slaughtered for performance evaluation analysis. This found that HADG increased body weight, fiber diameter, eye area, improved amino acid (histidine, arginine, valine, isoleucine, essential acid/total acid, acid/nonessential acid), fatty (linoleic behenic arachidonic acid) composition enhanced enzymes (pepsase, lipase, xylanase, amylase, carboxymethyl cellulose) promoted efficient fermentation (p < 0.05). Analysis populations indicated a notable increase Prevotella levels lambs. Furthermore, markers Schwartzia Streptococcus exhibited significant correlations differential traits. transcriptome correlation between turquoise module host phenotypes, particularly weight. Additionally, metabolism is primarily concentrated black module; however, it exhibits phenotype yellow Moreover, metabolites, microbes, phenotype, transcripts significantly correlated In conclusion, interactions among muscle, promote fermentation, which turn regulate transcriptional activity modify profiles both muscle. PCK1, SPP1, FGF7, NR4A1, DUSP5, GADD45B, etc., can be candidate genes finding provides theoretical basis further exploiting production potential Hu

Language: Английский

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Secretome Analysis: Reading Cellular Sign Language to Understand Intercellular Communication

Molecular & Cellular Proteomics, Journal Year: 2023, Volume and Issue: 23(1), P. 100692 - 100692

Published: Dec. 10, 2023

•Cell type-specific and proximity biotin labeling enables secretome characterization.•Glycan-mediated analysis requires carefully controlled interpretation.•Recent trends to perform in vivo.•Computational methods are critical interpret cellular organismal secretion. A significant portion of mammalian proteomes is secreted the extracellular space fulfill crucial roles cell-to-cell communication. To best recapitulate intricate multi-faceted crosstalk between cells a live organism, there an ever-increasing need for study protein secretion model systems that include multiple cell types. In addition, posttranslational modifications further expand complexity versatility This review aims summarize recent strategies employ coculture, chemical biology tools, enrichment, proteomic characterize composition function secretomes. all geared towards gaining better understanding vivo mediated by secretory signaling. The term was first used year 2000 designate processes bacteria Bacillus subtilis (1Tjalsma H. Bolhuis A. Jongbloed J.D. Bron S. van Dijl J.M. Signal peptide-dependent transport subtilis: genome-based survey secretome.Microbiol. Mol. Biol. Rev. 2000; 64: 515-547Google Scholar) has since become generally describe global group proteins secreted, released, or shed into environment cell, tissue, organ, organism at any given time. It been estimated proteome encompasses nearly 3000 >2000 localized plasma membrane, collectively representing some 25% (2Uhlen M. Fagerberg L. Hallstrom B.M. Lindskog C. Oksvold P. Mardinoglu et al.Proteomics. Tissue-based map human proteome.Science. 2015; 3471260419Google Scholar, 3Uhlen Karlsson M.J. Hober Svensson A.S. Scheffel J. Kotol D. al.The secretome.Sci. Signal. 2019; 12eaaz0274Google Scholar). trafficking these through pathway energetically expensive process, involve >250 needed after completion synthesis translocate endoplasmic reticulum (ER) Golgi, while assembling disulfide bonds adding N- O-linked glycans (4Gutierrez Feizi Li Kallehauge T.B. Hefzi Grav L.M. al.Genome-scale reconstructions predict metabolic costs limitations secretion.Nat. Commun. 2020; 11: 68Google expenditure warranted fact range important functions key proper functioning its niche, eventually entire organism. Specifically, comprises large variety bioactive molecules such as enzymes, hormones, antibodies, matrix (ECM) provide scaffolding ECM play regulating cell–cell cell–ECM interactions (3Uhlen 5Sainio Jarvelainen Extracellular matrix-cell interactions: focus on therapeutic applications.Cell 66109487Google 6Naba Ten years proteomics: accomplishments, challenges, future perspectives.Mol. Cell Proteomics. 2023; 22100528Google class constituted growth factors cytokines signal recipient induce specific response. not only required maintain tissue homeostasis healthy (as stipulated below) but also diseases like cancer where constitute organizing principle among cells, stroma, immune tumor microenvironment (7Propper D.J. Balkwill F.R. Harnessing chemokines therapy.Nat. Clin. Oncol. 2022; 19: 237-253Google 8Padgaonkar Shendre Chatterjee Banerjee Cancer secretome: finding out hidden messages secretions.Clin. Transl. 25: 1145-1155Google 9Robinson J.L. Uhlen Nielsen systematic investigation malignant diagnostic potential secretome.Cell Rep. 26: 2622-26235.e5Google Knowing sustain mutual therefore provides insight fundamental aspects maintenance onset disease may clues intervention interfering this network 10Cox T.R. cancer.Nat. Cancer. 2021; 21: 217-238Google Furthermore, it worth noting body fluids blood cerebrospinal fluid organs throughout body, putting center stage biomarker discovery. aim overview have emerged recently enrichment characterization proteins, including their modifications. we discuss application recapitulation systemic vivo. Secretory can either autocrine paracrine fashion host essential homeostasis, development, response stress. signaling, produces soluble mediator binds receptor same thereby completing self-sufficient form auto-regulation. For instance, production transforming factor-beta (TGFβ) well-studied yet intriguing case bi-phasic self-regulation (Fig. 1, Left). early stages cancer, TGFβ tumor-inhibitory suppressing cycle progression promoting apoptosis. However, late stages, turns increase invasiveness metastasis (11Massague TGFbeta cancer.Cell. 2008; 134: 215-230Google Paracrine signaling produced one acting another within diffusion radius enable outcome dependent population allows more complex fine-regulated with regulatory points. interferon-gamma (IFNγ) most well-understood mediators Right). While specialized IFNγ restricted almost other types receptors receive react (12Gocher A.M. Workman C.J. Vignali D.A.A. Interferon-gamma: teammate opponent tumour microenvironment?.Nat. Immunol. 22: 158-172Google ensures effectively modify successful elimination threats body. An extensively studied repair. Since repertoire documented promote proliferation migration, congruent secretions stimulate wound healing skin regeneration (13Gwam Mohammed N. Ma X. Stem secretome, regeneration, clinical translation: narrative review.Ann. Med. 9: 70Google On hand, preconditioning mesenchymal stromal shown produce different secretomes, be use (14Ferreira J.R. Teixeira G.Q. Santos S.G. Barbosa M.A. Almeida-Porada G. Goncalves R.M. Mesenchymal influencing pre-conditioning.Front. 2018; 2837Google Scholar), alluding possibility using secretomes under certain stimuli treat diseases. Particularly repair desirable naturally inefficient, utility heavily investigated. stem explored therapies trauma, stroke, neurodegenerative conditions spinal cord traumatic brain injuries, ischemic Parkinson's (15Pinho A.G. Cibrao Silva N.A. Monteiro Salgado A.J. basic insights opportunities CNS disorders.Pharmaceuticals (Basel). 13: 31Google Skeletal muscles secrete sets depending state physical exercise, during myogenesis, dystrophin deficiency, muscle atrophy, insulin stimulation (16Florin Lambert Sanchez Zappia Durieux Tieppo skeletal cells: review.Osteoarthr. Cartil. Open. 2100019Google Moreover, tested tendon ligament treatment (17Rhatomy Prasetyo T.E. Setyawan R. Soekarno N.R. Romaniyanto F. Sedjati A.P. al.Prospect conditioned medium (secretome) healing: review.Stem Cells 895-902Google Collectively, examples demonstrate rich source therapeutics regenerative therapy. Not do support healing, regulate organization remodeling. myocardial diseases, FGF2, VEGF, IL-11 critically cardiac remodeling (18Segers V.F.M. De Keulenaer G.W. Autocrine remodeling: targets.J. Am. Heart Assoc. 10e019169Google Dysregulation manifest pathophysiological mechanisms hypertrophy, fibrosis, inflammation. mammary gland development organization, which dysregulated breast (19Rosen Roarty K. development: what learn about intratumoral heterogeneity?.Breast Res. 2014; 16: 202Google pancreas endocrine alpha-cells beta-cells thought take mutually exclusive glucagon production. Yet, histological proximity, alpha engage indirectly beta-cell (20Holter M.M. Saikia Cummings B.P. Alpha-cell regulation secretion.Front. Endocrinol. (Lausanne). 13934775Google Such developmental very prevalent animals. fact, long time, limited animals, whereas species exclusively rely quorum sensing communicate. Recent studies unified two similar genetic circuits control many quorum-sensing essentially extreme ends common spectrum (21Doganer B.A. Yan L.K.Q. Youk sensing: spectrum.Trends 2016; 262-271Google Secreted they players pathological processes. notably includes constitutes niche closely interact releasing various cytokines, chemokines, decisive role survival tumors (22Hanahan Hallmarks cancer: new dimensions.Cancer Discov. 12: 31-46Google 23Hinshaw D.C. Shevde L.A. innately modulates progression.Cancer 79: 4557-4566Google Additionally, exploit release proteases protein-modifying enzymes affect stiffness, turn drive transformation growth, enhance epithelial-to-mesenchymal transition metastasis, drug resistance (24Winkler Abisoye-Ogunniyan Metcalf K.J. Werb Z. Concepts remodelling metastasis.Nat. 5120Google Immune components microenvironment, mounting evidence indicates both innate adaptive (25Ren Zhang Y. Siemers Insights gained from single-cell microenvironment.Annu. 39: 583-609Google cell-secreted will pave way improved approaches target simultaneously, increasing likelihood design effective interventions patients (26Berraondo Sanmamed M.F. Ochoa M.C. Etxeberria I. Aznar Perez-Gracia al.Cytokines immunotherapy.Br. 120: 6-15Google 27Roma-Rodrigues Mendes Baptista P.V. Fernandes A.R. Targeting therapy.Int. Sci. 20: 840Google 28Jiang Wang Deng Xiong Ge Xiang B. al.Role PD-L1/PD-1-mediated escape.Mol. 18: 10Google As if secretion-mediated enough, functionally different, dictated interactions, substrates present uniquely space. moonlighting adds layer mystery understand intercellular (29Cohen Chirico W.J. Lipke P.N. Through back door: unconventional secretion.Cell Surf. 6100045Google Protein exterior distinguished proceed classical non-classical ways. Classically directed peptides (30Coleman Inukai Inouye Dual peptide transfer across membrane.Cell. 1985; 43: 351-360Google These typically short sequences 16 30 amino acids N terminus shuttle newly synthesized polypeptide chains path. usually consists positively charged n-region, hydrophobic h-region, peptidase recognition site (31Inouye Soberon Franceschini T. Nakamura Itakura Role positive charge amino-terminal region membrane.Proc. Natl. Acad. U. 1982; 3438-3441Google 32Guo Sun Shu al.Positive n-region contributes efficient post-translational translocation small preproteins.J. Chem. 293: 1899-1907Google destined cleaved membrane fusion exterior. steers nascent ER subsequently Golgi apparatus, cleavage functionalization occur. During transit, glycosylations added, processed, trimmed endow boost stability harsh (33Benham reticulum.Cold Spring Harb. Perspect. 2012; 4a012872Google fully modified glycosylated bud off trans-Golgi vesicles, COPII Rab then direct vesicle membranes proteinaceous contents vesicles released (34Ramazanov B.R. Tran M.L. von Blume Sending TGN.Curr. Opin. 71: 55-62Google Although majority follow pathway, much 40% contain identifiable bypass (35Grieve Rabouille bypass: skirting around heart secretion.Cold 2011; 3: a005298Google 36Dimou E. Nickel W. Unconventional eukaryotic secretion.Curr. 28: R406-R410Google 37Rabouille Pathways secretion.Trends 2017; 27: 230-240Google Non-classical modes 'Golgi bypass' increasingly reported emerging so previously anticipated (38Villarreal Mendez O. Salvans Gregori Baselga Villanueva major contributor line secretomes.Mol. 2013; 1046-1060Google ectodomain shedding, process domain fate membrane-resident proteolytic (39Lichtenthaler S.F. Lemberg M.K. Fluhrer Proteolytic shedding mammals-hardware, concepts, developments.EMBO 37: e99456Google mechanistically example γ-secretase amyloid precursor ectodomains results accumulation plagues Alzheimer's (40Zhou Yang Guo Zhou Q. Lei Shi Recognition gamma-secretase.Science. 363: eaaw0930Google last decade, (EVs) garnered lot attention, excellent biomarkers liquid biopsies explain organotropic distribution (41Hoshino Costa-Silva Shen T.L. Rodrigues Hashimoto Tesic Mark al.Tumour exosome integrins determine metastasis.Nature. 527: 329-335Google EVs membrane-bound point clearly distinct mechanism secretion, compared Golgi-independent free instead (42Filaquier Marin Parmentier Villeneuve Roads hubs 75102072Google 2). note due biogenesis path EVs, retain relatively encapsulated still protect even outside (43Zhang Liu Lin al.A vesicle-mediated secretion.Cell. 181: 637-652.e15Google EV templated sequence highly state, fitness, external poorly predictable. Thus, changes extremely dynamic states molecular triggers. three discussed above, consider flux whether constitutive inducible. Most basal level biological likely environment. Inducible involves triggered presynthesized loads observed neuronal transduction neurotransmitters (44White K.A. Kim B.N. Quantifying neurotransmitter single-vesicle resolution high-density complementary metal-oxide-semiconductor electrode array.Nat. 431Google entero- neuro-endocrine (45Xie Jones K.L. Rayner C.K. Wu Enteroendocrine hormone control: importance gut stimulation.Pharmaceutics. 790Google 46Yoo E.S. Yu Sohn J.W. Neuroendocrine appetite metabolism.Exp. 53: 505-516Google broadly controls behavior coordinating motor movements, language affective behavior, trigger system respond necessitate immunological neuroendocrine enteroendocrine together diet metabolism, energy balance homeostasis. evident prompted 3). cannot done directly because organ involving types, culture vitro useful mono-culture or, increasingly, coculture systems. introduced enrich analytical depth, exploiting affinity handle designing sophisticated tools labeling. Finally, when combined engineering, starting We here salient literature 3), highlighting methodological merits, questions, indicating challenges future. long-standing identify despite general shortcoming 2D simplified representation bottleneck experiments presence bovine serum constituents media. quantitative perspective, reach concentration 0.05 0.1 μg/μl without stimulation, divided over hundreds thousands species. Full 10% concentrations 5-6 μg/μl, >95% top 10 abundant proteins. drastic imbalance abundance creates problem low abundance–secreted masked high artefacts, hampering detection identification mass spectrometry. partially circumvented omitting serum; however starvation create stress condition distorts (47Shin Rhim Kwon Choi S.Y. Shin Ha C.W. al.Comparative differentially serum-free serum-containing media BONCAT pulsed SILAC.Sci. 3096Google 48Eichelbaum Winter Berriel Diaz Herzig Krijgsveld Selective analysis.Nat. Biotechnol. 30: 984-990Google Use SILAC-labeled distinguish residual employed, example, investigate beta-secretase 2 (BACE2) melanoma (49Matafora V. Farris Restuccia Tamburri Martano Bernardelli al.Amyloid aggregates accumulate modulating YAP activity.EMBO 21e50446Google show pattern (SILAC-labeled) astrocytes altered few hours, type (unlabeled) neurons were added classical, unconventional, (50Stiess Wegehingel Nguyen Bradke Cambridge S.B. dual SILAC strategy quantifying cell-cell induced secretion.J. Proteome 14: 3229-3238Google circumvent negative effects extended periods starvation, approach decouple (exposure cytokines) depletion, removing h before harvest (51Knecht Eberl H.C. Bantscheff Interval-based secretomics unravels acute-phase hepatocyte systems.Mol. 21100241Google way, authors could profiles cytokine-induced 72 period. Even eliminating serum, trace amounts remnant identified sensitive LC-MS/MS. cases, consensus field search data against database experimental (i.e., human, mouse, etc) concatenated sequences, hit removed. caveat procedure share similarity eliminated, calling caution. Compared altogether, powerful alternative devised selectively originating cultured serum. display significantly enhanced coverage depth. concept, intrinsic biosynthetic machinery incorporate non-natural via clickable reactive groups (i.e. azides alkynes), bioorthogonal non-canonical acid tagging (BONCAT) (52Dieterich Link Graumann Tirrell D.A. Schuman E.M. noncanonical (BONCAT).Proc. 2006; 103: 9482-9487Google Methionine azido-homoalanine (AHA) immensely specifically capture quantities (48Eichelbaum 53Eichelbaum Combining click-chemistry analysis.Methods 1174: 101-114Google Alkyne-containing homo-propargylglycine compatible BONCAT. Minimal AHA ensure incorporation initiator codon, average 3 methionines, good accessibility on-bead trypsin digestion, followed LC-MS/MS identification. attractive feature click chemistry coupling azide-bearing alkyne beads selective covalent bond stringent washing remove non-labeled background contaminants. Alternatively, occur alkyne-biotin subsequent azide-modified pool avidin purification. Pulse applied macrophages, quantify upon macrophage activation Moreov

Language: Английский

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