Deciphering the relationship between temperature and immunity

Discovery Immunology, Год журнала: 2024, Номер 3(1)

Опубликована: Янв. 1, 2024

Fever is a hallmark symptom of disease across the animal kingdom. Yet, despite evidence linking temperature fluctuation and immune response, much remains to be discovered about molecular mechanisms governing these interactions. In patients with rheumatoid arthritis, for instance, it clinically accepted that joint can predict progression. But was only recently demonstrated mitochondria stimulated T cells rise an extreme 50°C, potentially indicating cellular source localized 'fevers'. A challenge dissecting bidirectional interplay between immunity. Heat shock response found in virtually all organisms, activating protective pathways when are exposed elevated temperatures. However, threshold activates vary within same organism, human cells, particular, demonstrating differential sensitivity heat. Such inter-cellular variation may relevant given small but significant differences seen tissues, ages, sexes. Greater understanding how such perturbations mediate responses provide new explanations persistent questions as sex disparity prevalence. Notably, prevalence severity many maladies rising climate change, suggesting fluctuations interact on multiple levels. As global temperatures rising, our body falling, regarding temperature-immune interactions increasingly critical. Here, we review this aspect environmental better understand temperature's role subsequent risk disease.

Язык: Английский

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Transfer and fates of damaged mitochondria: role in health and disease

FEBS Journal, Год журнала: 2024, Номер unknown

Опубликована: Март 28, 2024

Intercellular communication is pivotal in mediating the transfer of mitochondria from donor to recipient cells. This process orchestrates various biological functions, including tissue repair, cell proliferation, differentiation and cancer invasion. Typically, dysfunctional depolarized are eliminated through intracellular or extracellular pathways. Nevertheless, increasing evidence suggests that intercellular damaged associated with pathogenesis diverse diseases. review investigates prevalent triggers mitochondrial damage underlying mechanisms transfer, elucidates role directional both physiological pathological contexts. Additionally, we propose potential previously unknown explore their prospective roles disease prevention therapy.

Язык: Английский

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Irisin Protects Musculoskeletal Homeostasis via a Mitochondrial Quality Control Mechanism

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(18), С. 10116 - 10116

Опубликована: Сен. 20, 2024

Irisin, a myokine derived from fibronectin type III domain-containing 5 (FNDC5), is increasingly recognized for its protective role in musculoskeletal health through the modulation of mitochondrial quality control. This review synthesizes current understanding irisin’s impact on biogenesis, dynamics, and autophagy skeletal muscle, elucidating capacity to bolster muscle strength, endurance, resilience against oxidative-stress-induced atrophy. The multifunctional nature irisin extends bone metabolism, where it promotes osteoblast proliferation differentiation, offering potential intervention osteoporosis other disorders. Mitochondrial control vital cellular particularly energy-demanding tissues. Irisin’s influence this process highlighted, suggesting integral maintaining homeostasis. also touches upon regulatory mechanisms secretion, predominantly induced by exercise, systemic effects as an endocrine factor. While therapeutic promising, need standardized measurement techniques further elucidation humans acknowledged. collective findings underscore burgeoning interest keystone candidate future strategies.

Язык: Английский

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Miquelianin, a main functional flavonoid of lotus leaf, induces thermogenic signature via p38‐PINK1‐PARKIN‐mediated mitophagy and mimicking NRF2 signaling during brown adipocyte differentiation

Food Frontiers, Год журнала: 2023, Номер 4(4), С. 1831 - 1844

Опубликована: Июнь 25, 2023

Abstract Adipocytes thermogenesis is an important mechanism for increasing energy expenditure. Here, screening of thermogenic activators (Sirt1 and Ucp1) investigated in C 3 H 10 T 1/2 cells revealed ethanol extract lotus leaf (LLE) may exert higher activity compared with that the other 11 ingredients. UPLC‐MS/MS analysis showed miquelianin was identified as main flavonoid compounds LLE (12.8%) therefore deserves further investigation. The results promoted lipolysis, enhanced programming (Sirt1, Ppargc1a, Prdm16, Cox7a, Nrf1, Cox2, Ucp1), induced brown‐like adipocyte formation (Fgf21, Cd137, Tmem26, Tbx1, Cd40, Cited1). Moreover, increased mitochondrial abundance, membrane potential, NAD + /NADH ratio, suggesting its potential mitochondria activity. We also observed improved quality by establishment dynamics (Mfn1, Mfn2, Opa1, Drp1, Fis1) subsequent suppression autophagy. Chemical inhibition experiment trigger browning via p38‐PINK1‐PARKIN‐mediated mitophagy. Furthermore, ML385‐treated cells, NRF2, HMOX1, TFAM, UCP1 were compromised treatment, NRF2 signaling necessary during miquelianin‐induced biogenesis. Together, our findings demonstrate induce programing suppressing mitophagy p38‐PINK1‐PARKIN mimicking signaling.

Язык: Английский

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The molecular mechanism of macrophage-adipocyte crosstalk in maintaining energy homeostasis

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Апрель 8, 2024

Interactions between macrophages and adipocytes in adipose tissue are critical for the regulation of energy metabolism obesity. Macrophage polarization induced by cold or other stimulations can drive metabolic reprogramming adipocytes, browning, thermogenesis. Accordingly, investigating roles maintenance homeostasis is development novel therapeutic approaches specifically targeting disorders such as Current review outlines macrophage not only regulates release central nervous system inflammatory factors, but controls mitochondrial function, factor that induce maintain homeostasis. We also emphasized on how conversely motivate macrophage. Exploring interactions may provide new strategies management obesity-related diseases.

Язык: Английский

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Lipid-associated macrophages reshape BAT cell identity in obesity

Cell Reports, Год журнала: 2024, Номер 43(7), С. 114447 - 114447

Опубликована: Июль 1, 2024

Язык: Английский

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GPR84-mediated signal transduction affects metabolic function by promoting brown adipocyte activity

Journal of Clinical Investigation, Год журнала: 2023, Номер 133(24)

Опубликована: Окт. 19, 2023

The G protein-coupled receptor 84 (GPR84), a medium-chain fatty acid receptor, has garnered attention because of its potential involvement in range metabolic conditions. However, the precise mechanisms underlying this effect remain elusive. Our study shed light on pivotal role GPR84, revealing robust expression and functional significance within brown adipose tissue (BAT). Mice lacking GPR84 exhibited increased lipid accumulation BAT, rendering them more susceptible to cold exposure displaying reduced BAT activity compared with their WT counterparts. vitro experiments primary adipocytes from GPR84-KO mice revealed diminished thermogenic genes O2 consumption. Furthermore, application agonist 6-n-octylaminouracil (6-OAU) counteracted these effects, effectively reinstating adipocyte activity. These compelling vivo findings converge highlight mitochondrial dysfunction as cause anomalies mice. activation induced an increase intracellular Ca2+ levels, which intricately influenced respiration. By modulating levels respiration, acts potent molecule involved suggest that is therapeutic target for invigorating ameliorating disorders.

Язык: Английский

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Xiasangju alleviate metabolic syndrome by enhancing noradrenaline biosynthesis and activating brown adipose tissue

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Март 21, 2024

Metabolic syndrome (MetS) is a clinical condition associated with multiple metabolic risk factors leading to type 2 diabetes mellitus and other diseases. Recent evidence suggests that modulating adipose tissue adaptive thermogenesis may offer therapeutic potential for MetS. Xiasangju (XSJ) marketed drug dietary supplement used the treatment of disease anti-inflammatory activity. This study investigated effects XSJ underlying mechanisms affecting activation brown (BAT) in The results revealed ameliorated MetS by enhancing glucose lipid metabolism, reduced body weight abdominal circumference, decreased liver index, improved blood tolerance. administration stimulated catecholamine biosynthesis, increasing noradrenaline (NA) levels activating NA-mediated proteins BAT. Thus, BAT enhanced oxidative phosphorylation (OXPHOS). Moreover, induced changes gut microbiota composition, an increase Oscillibacter abundance decrease Bilophila, Candidatus Stoquefichus, Holdemania, Parasutterella Rothia. upregulated intestinal tight junctions corresponding lower serum lipopolysaccharide (LPS), tumor necrosis factor α (TNF-α) monocyte chemoattractant protein-1 (MCP-1) interleukin-6 (IL-6) maintain NA signaling transport. In summary, alleviate promoting ultimately boost energy metabolism through strengthening barrier integrity reducing low-grade inflammation. These findings suggest has as natural agent

Язык: Английский

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Myostatin regulates energy homeostasis through autocrine- and paracrine-mediated microenvironment communications

Journal of Clinical Investigation, Год журнала: 2024, Номер 134(16)

Опубликована: Июнь 18, 2024

Myostatin (MSTN) has long been recognized as a critical regulator of muscle mass. Recently, there increasing interest in its role metabolism. In our study, we specifically knocked out MSTN brown adipose tissue (BAT) from mice (MSTNΔUCP1) and found that the gained more weight than did controls when fed high-fat diet, with progressive hepatosteatosis impaired skeletal activity. RNA-Seq analysis indicated signatures mitochondrial dysfunction inflammation MSTN-ablated BAT. Further studies demonstrated Kruppel-like factor 4 (KLF4) was responsible for metabolic phenotypes observed, whereas fibroblast growth 21 (FGF21) contributed to microenvironment communication between adipocytes macrophages induced by loss MSTN. Moreover, MSTN/SMAD2/3-p38 signaling pathway mediated expression KLF4 FGF21 adipocytes. summary, findings suggest adipocyte-derived regulated BAT thermogenesis via autocrine paracrine effects on or macrophages, ultimately regulating systemic energy homeostasis.

Язык: Английский

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Metformin delays the decline in thermogenic function of brown adipose tissue in a mouse model of Hutchinson-Gilford progeria syndrome

Experimental Gerontology, Год журнала: 2025, Номер 201, С. 112702 - 112702

Опубликована: Фев. 6, 2025

Brown adipose tissue (BAT) is the primary site for non-shivering thermogenesis in body and plays a crucial role maintaining core temperature. However, its function gradually declines with age. To mitigate age-related decline BAT thermogenic capacity, we treated progeroid mice metformin to investigate potential mechanisms by which can slow reduction function. We found that mice, after receiving treatment, showed significant improvement senescent state of brown adipocytes through activation SIRT1, effectively reduced mitochondrial oxidative stress. Additionally, slowed UCP1 expression levels tissue, thereby capacity mice. Moreover, inflammatory responses around cells, further improving overall tissue. These findings suggest down aging process targeting enhancing capacity.

Язык: Английский

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